Hepatitis Ebook

Alternative Hepatitis C Treatments

The therapeutic goals of Natural treatment for Hepatitis C are as follows: Decrease iral load Normalize liver enzyme levels. Enhance/regulate immune system function. Strengthen and promote healthy liver function. Protect the liver, prevent further damage. Virological response; i.e. viral clearance, viral reduction or elimination of the virus. Starve the virus by limiting levels of iron. Optimizing cellular levels of glutathione in the body, making detoxification of the liver possible and enhancing the immune system. Stimulate regeneration of the damaged liver cells. Use of antioxidants to combat the effects of free-radicals generated by the virus. Reduce inflammation. Slow viral replication. Replace all of the inflammation-damaged liver cells. Regulate immune function/prevent auto-immune problems. Cancer preventative measures. Reverse fibrosis to prevent and improve cirrhosis

Alternative Hepatitis C Treatments Summary

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Hepatitis C Comorbidity

In developed countries, HAART has largely transformed HIV AIDS from a fatal to a chronic illness, thus allowing the emergence of significant comorbi-dities that may affect CNS function. Hepatitis C virus (HCV) infection is a prevalent comorbidity in HIV patients, especially among intravenous drug users, so we will focus primarily on this comorbidity and its cognitive effects. HCV has been shown to cause neuropsychological deficits among HIV- and HCV-positive individuals. Among advanced seropositive participants of the Manhattan HIV Brain Bank, HIV-and HCV-positive coinfected patients were more likely to receive a diagnosis of HIV-associated dementia and have greater impairment in executive functioning (Ryan et al., 2004). These cognitive differences were associated with HCV serology but did not correlate with indices of liver disease severity. Deficits in learning, motor skills (Cherner et al., 2005), attention and concentration, and psychomotor speed (von Geisen et al., 2004 Perry et...

Autoimmunity in chronic hepatitis C

Hepatic infection with HCV is known to induce several hepatic and extrahepatic autoimmune manifestations. Extrahepatic manifestations include mixed cryoglo-bulinaemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, Sjorgen syndrome and autoimmune thyroid disease 4 . Not surprisingly, numerous autoantibodies are found to be associated with chronic hepatitis C, i.e. antinuclear antibody (ANA), smooth muscle antibody (SMA), LKM-1 and antithyroid autoantibodies 5 . However, in the majority of cases, these antibodies are not markers of real autoimmune diseases. LKM1 autoantibodies, for example, are detected in patients with AIH-2 and in 0-7 of patients with chronic hepatitis C 6 . Patients with LKM1 autoantibodies and chronic HCV infection show clinical features which are typical for an HCV infection and pathogenesis is clearly different from that in patients with AIH. They are usually older than 40 years, inflammatory activity is low and response to corticosteroids is...

Autoimmunity in chronic hepatitis D

Two RNA viruses causing hepatitis are known HCV and hepatitis D virus (HDV). In contrast to infections with DNA viruses, both RNA viruses are strongly associated with autoimmune manifestations. While HCV infection is associated with LKM1 autoantibodies, HDV infection is associated with LKM3. These LKM3 auto-antibodies are detected in 13 of all patients with chronic hepatitis D and are found also in AIH-2, but there is no overlap of HCV infection with LKM3 autoantibodies. The molecular target of the LKM3 autoantibody was identified as uridine diphosphate (UDP)-glucuronosyltransferases of family 1 (UGT1) 9, 10 . Interestingly, LKM3 autoantibodies recognize a conformation-dependent epitope of amino acids 264-373. The presence of LKM1 autoantibodies in HCV infection and of LKM3 autoantibodies in HDV infection demonstrates that different hepatotropic viruses are able to induce specific autoantibodies, which are not detected in other virus infections. This specificity cannot be explained by...

Other Hepatitis Viruses

There are several other newly discovered viruses that have been added to the hepatitis alphabet of viruses, although subsequent research has shown not all of them belong in the group. This section briefly describes some of those viruses that may be shown in the future to be transmitted in utero or perinatally. GB Virus C or Hepatitis G Virus GB virus C (GBV-C) or hepatitis G virus was initially discovered using PCR-based techniques on stored blood specimens from patients with non-A to E hepatitis but was

Molecular biology of HCV

HCV belongs to the genus Hepacivirus in the Flaviviridae family of viruses, together with Pestiviruses and Flaviviruses (Ohba et al., 1996). HCV genome is a 9.6 kb uncapped, linear, single-stranded RNA molecule of positive polarity (Kato et al., 1990 Takamizawa et al., 1991) that serves as template for both translation and replication. The HCV-RNA contains two untranslated regions at the 5' and 3' ends and a single ORF that encodes for a 3010-3030 amino acid polyprotein that is processed post-transcriptionally by host- and virus-encoded proteinases to produce the structural (core, E1 and E2) and nonstructural (p7, NS2-NS5) viral proteins (Fig. 4). Translation of viral proteins depends on an internal ribosome entry site (IRES) in the 5' untranslated region (5' UTR), which has a complex RNA structure that directly interacts with the 40S ribosomal subunit during translation initiation (Pestova et al., 1998). Comparison of nucleotide sequences of HCV variants isolated from different...

Natural history of HCV infection

Clinically, acute hepatitis C is similar to other forms of acute viral hepatitis. The incubation period, from infection to the onset of the symptoms, ranges from 7 to 20 weeks (Alter et al., 1989). The first marker of HCV infection that appears in serum is HCV-RNA that can be detected within 1-2 weeks after exposure (Hino et al., 1994). Later on, serum aminotransferase levels increase followed by appearance of antibodies to HCV (anti-HCV). In general, the first anti-HCV antibodies detected are of IgM class (Quiroga et al., 1991) but in some cases, the appearance of anti-HCV IgM coincides with that of anti-HCV IgG (Brillanti et al., 1993). If acute HCV infection resolves, the HCV-RNA and the anti-HCV IgM become undetectable in serum, while titers of the anti-HCV IgG decrease and, in some cases, may become undetectable several years after the resolution of the acute infection (Takaki et al., 2000). In 70-80 of patients acutely infected with HCV, the infection becomes chronic (Puoti et...

Hepatitis viral

Acute hepatitis (typically presenting as acute jaundice) is generally caused by hepatitis A, B, C and E viruses, which belong to different virus families. These viruses also differ in their (a) modes of transmission, (b) geographical and epidemiological patterns, which explain various age-related incidence profiles, and (c) propensity to result or not in chronic infections. Hepatitis D (not detailed any further here) is a particular case, being caused by a defective virus that can replicate and cause disease only in individuals already co-infected or chronically infected with the hepatitis B virus. Table 5.5 illustrates the main differences between the hepatitis viruses. Table 5.5 Characteristics of the hepatitis viruses Table 5.5 Characteristics of the hepatitis viruses Hepatitis A Fulminant hepatitis Hepatitis B Fulminant hepatitis Chronic hepatitis, cirrhosis, liver cancer Hepatitis C Fulminant hepatitis Chronic hepatitis, cirrhosis, liver cancer Hepatitis E Fulminant hepatitis...

Hepatitis A Virus

Hepatitis A virus (HAV) is a member of the Picornavirus family. It is a single-stranded, plus sense (directly translated into protein) ribonucleic acid (RNA) virus approx 30 m in diameter. The HAV RNA has 7500 nucleotides and is translated to a single polyprotein that is cleaved by its own protease to yield individual viral proteins. Hepatitis A Hepatitis B Hepatitis C Serum HCV IgG, serum HCV RNA (qualitative and quantitative) Hepatitis D Hepatitis E Infants who demonstrate signs of hepatitis in the newborn period with a symptomatic mother may be tested for IgM antibody to HAV. Proper precautions to limit the exposure of others should be taken.

Hepatitis B Virus

Hepatitis B virus (HBV) is a member of the Hepadnavirus family. It is a large deoxyribonucleic acid (DNA) virus with a circular chromosome that undergoes an RNA stage in the host cell during its replicative cycle. It subsequently produces viral DNA, which ultimately leads to synthesis of the viral proteins. The major proteins involved in HBV infection are the surface antigen (HBsAg), core antigen (HBcAg), and the e antigen (HBeAg). The HBsAg is an element of the outer surface of the virus HBcAg and HBeAg are different forms of the same polyprotein. HBcAg is made up of subunit proteins that form the genomic core of the full virus HBeAg is a truncated form of this protein that is thought to play a role in signaling for viral replication (4). Mothers who exhibit symptoms of acute hepatitis, including fever, jaundice, abdominal pain, and who by history engaged in high-risk behaviors for acquisition of HBV (e.g., promiscuous sexual practices, sex with a known HBV carrier, or intravenous...

Hepatitis C Virus

Hepatitis C virus (HCV) is a flavivirus that was determined in 1989 to be the major cause of transfusion-related non-A, non-B hepatitis. It is a single-stranded, plus sense RNA virus with a genome size of approx 9500 bp. It encodes for a single large polyprotein that is cleaved to form individual viral proteins. The virus displays marked heterogeneity, with six distinct genotypes, and numerous quasi-species attributable to hypervariable regions of the two envelope proteins that readily mutate. Currently, there is no established cell culture system for HCV, and chimpanzees are the only available laboratory animal model, so little is still known about the mechanisms of infection (2,3,8). HCV is spread primarily by blood-borne contact with infected blood. The most common risk factors identified are intravenous drug use and blood transfusion or transplantation prior to 1992. Sexual acquisition of the virus is a very inefficient form of transmission and has not been proven definitively in...

Hepatitis D Virus

Hepatitis D virus (HDV) is replication-defective RNA virus. HDV requires co-infection with HBV to complete assembly of new HDV viral particles (22). HDV infection presents as acute symptoms of hepatitis, with jaundice, fever, and abdominal pain. It can also present with acute signs of hepatitis in a chronic carrier of HBV who was previously well (2,22).

Hepatitis E Virus

Hepatitis E virus (HEV) is still a relatively newly discovered virus. HEV is a small, nonenveloped, single-stranded plus sense RNA virus. The viral genome includes 7500 bp that code for three sets of genes. HEV is genetically related to the Calicivirus family. It has two distinct geographic subtypes, the Asian and Mexican strains (23,24). HEV is transmitted by fecal-oral contact. It occurs primarily in outbreaks in underdeveloped countries but can also occur sporadically. The source of the outbreaks is contaminated water, and in endemic areas, HEV accounts for most cases of acute hepatitis. Most patients diagnosed with HEV in the United States are travelers who acquired the virus in a foreign country. The attack rate of HEV appears to be about 50 times less than that of HAV in infected households (1 vs 50-75 ) (23,24). HEV usually causes acute hepatitis in approx 75 of patients infected. The incubation period ranges from 15 to 65 days, and symptoms vary from mild to severe. Fulminant...

Asad Ansaria Adriana Weinbergb

Congenital infection with HHV-6 differ from post-natal infections in terms of being mainly asymptomatic, demonstrating viral reactivation in 10 at birth, and frequent persistence of HHV-6 DNA in follow-up blood samples. One-third of congenital infections are HHV-6A (Hall et al., 2004). Sporadic cases of exanthema subitum, fulminant hepatitis, fatal pneumonitis with immunodeficiency and seizures with adverse outcome have been reported in the neonatal period, albeit rare (Knox et al., 1995 Mendel et al., 1995 Lanari et al., 2003 Yoshikawa et al., 2004). HHV-7 has not been associated with congenital and neonatal infections (Hall et al., 2004 Weinberg et al., 2005). Mendel I, Matteis M, Bertin C, Delaporte B, Maguer D, Collandre H, Buffet-Janvresse C. Fulminant hepatitis in neonates with human herpesvirus 6 infection. Pediatr Infect Dis J 1995 14 993-997.

Molecular biology of HBV

Squirrel (ground squirrel hepatitis virus) (Marion et al., 1980), woodchucks (wood-chuck hepatitis virus) (Summers et al., 1978), Arctic ground squirrels (Arctic squirrel hepatitis virus) (Testut et al., 1996) and wolly monkeys (Landford et al., 1998). Other hepadnaviruses have been isolated from birds, such as Pekin ducks (duck hepatitis B virus) (Mason et al., 1980), gray herons (heron hepatitis B virus) (Sprengel et al., 1988) and storks (stork hepatitis B virus) (Pult et al., 2001). Owing to the homology in DNA sequences and genome organization, hepadnaviruses-infecting mammals are grouped into the genus Ortohepadnavirus, while those found in birds are grouped into the genus Avihepadnavirus. The four overlapping OFRs in the HBV genome are termed ORF S, C, P and X. The ORF S contains three in frame initiation codons (Pre S1, Pre S2 and S) and encodes the three polypeptides (Large-L-, Middle-M- and Small-S-) that form the outer envelope of the virus. These three proteins have a...

Diagnosis of HBV infection

Testing for serum HBV-DNA is the best way to determine viral replication and persistence, although HBV-DNA assays are not recommended at present for the routine evaluation of patients with chronic HBV infection. Serum HBV-DNA is detected few days after infection and reaches the peak at the time at which clinical symptoms of acute hepatitis appears (Whalley et al., 2001). When infection is self-limited, HBV-DNA titers decrease dramatically although viral DNA may remain detectable in serum by PCR long years after the resolution of acute infection (Michalak et al., 1994 Cabrerizo et al., 1997 Yotsuyanagi et al., 1998). In patients with chronic HBV infection, viral DNA levels are high (detectable by hybridization-based techniques) in the HBeAg-positive phase and decline at the time of anti-HBe seroconversion, except in patients infected with precore or core promoter mutants. However, it must be stressed that HBV-DNA may remain detectable in serum by PCR even in those patients that resolve...

List of Contributors

Fundacion para el Estudio de las Hepatitis Virales Madrid, Spain Fundacion para el Estudio de las Hepatitis Virales Madrid, Spain Fundacion para el Estudio de las Hepatitis Virales Madrid, Spain Despite the introduction of efficacious vaccines against rubella, Varicella-zoster and hepatitis B viruses the use of effective drugs for the treatment of herpes, toxoplasma and Chagas diseases and the development of highly sensitive, specific and reproducible immunoassays and nucleic acid tests for the diagnosis of a variety of bacterial, viral and parasitic diseases, congenital infections continue to pose a substantial threat throughout the world. Congenital and other related diseases of the newborn remain important causes of malformation and death among infants worldwide. The incidence of intrauterine infections during pregnancy has been estimated to be about 14 when highly sensitive diagnostic procedures are used. Perinatal infections account for 2-3 of all congenital anomalies in western...

Varicella pneumonia

Although chickenpox is much less common in adults than in children, the infection is associated with greater morbidity, namely pneumonia, hepatitis, and encephalitis. The varicella pneumonia in pregnancy must be regarded as a medical emergency (Frangidis and Pneumatikos, 2004). The clinical course is unpredictable and may rapidly progress to hypoxia and life-threatening respiratory failure. Retrospective studies suggest that varicella pneumonia may be more severe, although not more frequent, in pregnant compared to non-pregnant women (Harris and Rhoa-des, 1965). A case control study of 18 pregnant women with varicella pneumonia and 72 pregnant controls with varicella but no pneumonia found that smoking and the occurrence of at least 100 skin lesions were risk factors for the development of pneumonia (Harger et al., 2002a).

Risk Factors and Cancer

Both DNA and RNA viruses are responsible for about 5 of human cancer but are a more common causes of cancer in animals where they play a central role in the identification of oncogenes.25'26 About 5 of adult T cell leukemias lymphomas are due to human lymphotropic virus type I27 while Epstein-Barr virus accounts for 10-15 of non-Hodgkin's lymphoma, Burkitt's lymphoma (almost all children in central Africa and 20 of cases occurring elsewhere), 35-50 of Hodgkin's disease, and 40-70 of nasopharyngeal carcinoma (especially in southern Chinese).28 Hepatitis B virus accounts for 40-60 of hepatocellular carcinoma and hepatitis C virus for 20-30 .29 Some subtypes of the human papilloma viruses (HPV16 and HPV18) account for 90 of cervical cancer. HPV infection is now recognized to be a sexually transmitted disease with special risk from early sexual exposure before the cervix is fully mature. HPV viruses cause benign warts and may be involved in cancers of the oral cavity and upper respiratory...

Diagnosing Infection By Serologic Means

When maternal titers of antibody are high (e.g., HIV-infected mothers may have anti-HIV titers that exceed 1 million), the time required for sufficient half-lives to pass to render an ELISA assay negative may take as long as 15-18 months. For example, an HIV ELISA test often is performed at a 1 100 dilution of serum. If the maternal titer is 4 million at birth, a 33,000 reduction in titer (which represents 15 half-lives or 15 x 23 345 days) would still yield a positive assay. In fact, the average time to deplete maternal HIV and hepatitis C antibody in the infant is about 9 months.

Isolation And Identification

The selection, transport, storage, and processing of the specimen are crucial for isolation attempts to be meaningful. The ideal specimen is taken from the site of the lesion or symptoms as early in the course of the illness as possible. The risk of fetal exposure or infection is determined by the status of the mother. Herpes I or II, enterovirus, rubella, and varicella-zoster virus (VZV) are some of the viruses that may be isolated and that are clinically relevant to the fetus or newborn. Other important agents such as hepatitis B virus, HIV, and parvovirus B-19 are either extremely difficult to culture or cannot be cultured. Cells grown in culture are the in vitro progeny of cells obtained from living tissue. Cultures are started from dissociated pieces of tissue placed in nutrient media in a sterile culture vessel. Cells may grow in suspension or adhere to the surface of the vessel. Adherent cultures form sheets of cells attached to a clear glass or plastic surface. Primary culture...

Special Stains And Molecular Techniques In The Diagnosis Of Infectious Agents

There have been considerable advances in the use of molecular techniques for rapid detection of pathogens, especially those that are fastidious or nonculturable. Some of the rewards of diagnostic molecular techniques include rapid turnaround time, increased specificity, enhanced sensitivity, ability to identify esoteric micro-organisms, quantitation, genotyping, and monitoring of drug resistance. Qualitative assays determine presence or absence of a nucleic acid consistent with the presence of an infectious agent. Polymerase chain reaction (PCR) replaces the conventional process of biological amplification (growth in culture) with enzymatic amplification, allowing identification of as few as 100 copies of a particular deoxyribonucleic acid (DNA) sequence (84). Reverse transcription PCR may be useful in detection of ribonucleic acid (RNA) virus infections, including hepatitis C virus, HIV, and enteroviruses (85,86). Because of the sensitivity, contamination is a constant threat, and...

HIVAssociated Dementia

One further word about neuropsychiatric manifestations of HIV hepatitis C virus (HCV) is highly comorbid with HIV, and HCV can create its own neuropsychiatric problems as well as exacerbate those caused by HIV. Screening for HCV is relatively straightforward, but current therapy for HCV infection is poorly tolerated and not effective for a substantial number of patients (Wainberg et al., 2003). Approximately four million people in the United States and probably more than 100 million worldwide are infected with HCV, yet it has been estimated that less than 30 of people with HCV know they are infected (National Institutes of Health Consensus Development Confer ence Panel, 1997). HCV is an important diagnosis of exclusion when treating neuropsychiatric complications of HIV.

Laboratory Assays For The Diagnosis Of Neonatal Herpes Simplex Virus Disease

Isolation of HSV by culture remains the definitive diagnostic method of establishing HSV disease. If skin lesions are present, a scraping of the vesicles should be transferred in appropriate viral transport media on ice to a diagnostic virology laboratory. Such specimens are inoculated into cell culture systems, which are then monitored for cytopathic effects characteristic of HSV replication. Other sites from which virus may be isolated include the CSF, urine, blood, stool or rectum, oropharynx, and conjuncti-vae (38). Duodenal aspirates for HSV isolation may be indicated in infants with hepatitis, necrotizing enterocolitis, or other gastrointestinal manifestations of disease. Typing of an HSV isolate may be done by one of several techniques but is not generally available outside research laboratories.

Waste disposal medical waste

Medical waste includes needles, scalpels, laboratory samples, disposable materials stained with body fluids, and body tissue. This waste requires special care in handling, since needles and scalpels can cut handlers and transmit diseases such as HIV AIDS, hepatitis B and C and viral haemorrhagic fevers. Medical waste should be burnt in an incinerator, preferably as close as possible to the source, e.g. within the clinic or hospital grounds, but also downwind of hospital buildings and dwellings.

Unmet Medical Needs

HIV and hepatitis B and C via intravenous use Overdoses HIV hepatitis B and C, endocarditis Overdoses substantial burden of medical illness compared to age- and gender-matched US population controls.70 Drug-related complications occur not only in public sector patients, but also in a community sample of patients enrolled in a health maintenance organization.71 Some of the widely accepted medical complications are summarized in Table 7. Drug abuse is a leading contributor to the spread of AIDS, HIV, and hepatitis C, and drug abuse treatment can reduce the spread of these illnesses.8 Not unexpectedly, intravenous drug use causes various surgical complications.72

Mary Ann Cohen and David Chao

In 1967 Lipowski provided a classification of commonly encountered problems at the medical-psychiatric interface that is still relevant to AIDS psychiatry today. These problems (with a modification of the fifth item, discussed in Chapter 1 of this book) include psychiatric presentation ofmedical illness, psychiatric complications of medical illnesses or treatments, psychological response to medical illness or treatments, medical presentation of psychiatric illness or treatments, and comorbid medical and psychiatric illness. These five problems have been illustrated with casevignettes in Chapter 1. Somepersons withHIVand AIDS have no psychiatric disorder, while others have a multiplicity of complex psychiatric disorders that are responses to illness or treatments or are associated with HIV AIDS (such as HIV-associated dementia) or co-morbid medical illnesses and treatments (such as hepatitis C, cirrhosis, or HIV nephropathy and end-stage renal disease). Persons with HIV and AIDS may...

Pharmacokinetics and toxicity

IFN-a side effects can be separated into acute and chronic toxicity (35). Acute toxicity is represented by a flu-like syndrome, characterized by fever, chills, bone pain, and headache. These side effects usually appear 2 to 4 h application IFN-a after. Acute side effects can be attenuated significantly by prophylactic application of acetaminophen at a dose of 500 to 1000 mg orally (po) taken 2 h before and 2 h after subcutaneous injection of IFN. Side effects are generally dose related but tend to disappear within days due to tachyphy-laxis. A less common side effect is gastrointestinal toxicity, such as nausea, vomiting, and diarrhea. Cardiovascular toxicity, such as hypotension, angina pectoris, or tachyarrhythmia, is also rarely observed. The chronic toxicity of IFN generally manifests as fatigue, depression, polyneuropathy, and asthenia. Autoimmune phenomena, such as autoimmune hepatitis or hypothyroidism, may also be observed during prolonged IFN-a therapy. Occlusion of retinal...

Risk Of Fetalneonatal Infection

Since the institution, about 30 years ago, of the recommendation for passive immunization of exposed newborns with VZIG as soon as possible after birth, it is rare for a newborn infant to die of disseminated varicella. Before VZIG became available, one study suggested a 20 fatality rate when the mother had onset of rash less than 4 days and up to 2 days after onset of rash at delivery (13). Infants in whom varicella is fatal often have a disseminated infection with pneumonia, extensive hemorrhagic skin vesicles, hepatitis, and thrombocytopenia. Mothers whose onset of rash is more than 48 hours after delivery may transmit varicella to their babies, but the disease is usually not severe because they transfer antibodies as well (7).

Sexually Transmitted Infections

Hepatitis B virus (HBV) can be acquired through consensual and nonconsensual sexual activity (210). Therefore, HBV vaccine should be offered to all adult victims of sexual assault (202). In children and young people, a risk benefit analysis will inform the decision regarding whether the vaccine should be offered. Regardless of whether prophylaxis is given, complainants should be counseled and offered baseline serological tests for syphilis, HBV, hepatitis C, and HIV, which will be repeated at the relevant periods after assault.

Adaptive Antitumor Responses

In transgenic models of hepatitis B-induced liver cancer, smoldering CD4+ and CD8 + T cell responses are required for progression of hepatocellular carcinoma (Nakamoto et al., 1998). Similarly, CD4 + T cells activated by normal cutaneous bacterial flora promote the evolution of squamous cell carcinoma in a human papilloma virus transgenic model (Daniel et al., 2003).

Role of Viruses in the Causation of Human Cancer

On the basis of this sort of evidence, some human cancers are considered to be caused by viral infection either directly or indirectly. By directly, I mean that the viral gene(s) can themselves cause cells to become malignant (sometimes also requiring the loss of a tumor suppressor gene). By indirectly, I mean that viral infection may simply cause the progression of malignant cell growth by producing an immunodeficiency state (e.g., the occurrence of non-Hodgkin's lymphoma in HIV-infected patients) or by stimulating the proliferation of already transformed cells. Sometimes viral infection acts in concert with other infectious agents or chemical carcinogens. Such is the case for malarial infection of Epstein-Barr virus (EBV)-infected patients and for aflatoxin exposure of individuals bearing the hepatitis B viral genome in their liver cells (see below). The types of

Consequences Of Congenital Or Acquired Human Herpesvirus 6 And 7 Infections

Several case reports have described fetuses or infants with HHV-6 infection, yet most have no abnormalities. Aubin et al. (25) first described in utero infection with HHV-6. These investigators examined 52 electively aborted fetuses from HIV-infected women from France and noted one fetus (26 weeks) with HHV-6 DNA distributed throughout fetal tissues. No abnormalities were identified. One study from Japan identified HHV-6 antigens in tissues from 2 of 30 (7 ) fetuses spontaneously aborted at 6-12 weeks fetal abnormalities were not described (26). HHV-6 DNA has also been found in fetal tissues of two of eight cases (25 ) of fetal hydrops (17 and 19 weeks of gestation) (27). However, both fetuses also had a chromosomal abnormality (Down syndrome and Turner's syndrome) possibly contributing to the hydrops. Fulminant hepatitis in two neonates (aged 3 and 5 days) has purported to be linked to congenital HHV-6 infection based on HHV-6 viremia in mother and baby (28) further...

Epidemiology And Demographics

The role of hepatitis viruses in the etiology of classic idiopathic AA.7 AA has been described in Africa and India, where it may be also more prevalent than in the West, but exact epidemiologic studies are not available. In the United States, AA does not appear to show an ethnic predilection.

Classification Of Aa Based On Etiology And Pathophysiologic Mechanisms

In many respects, clinical and pathophysiologic features of AA suggest a possible infectious etiology. Most commonly, viruses have been implicated. Over the years, many of the suggested agents have been excluded as etiologic factors. The search for AA agents has been extensive. Hepatitis B and A were proven not to be the causative agent for typical AA. Similarly, cytomegalovirus (CMV), although certainly capable of producing bone marrow suppression under certain clinical circumstances, such as following stem cell transplantation, is not responsible for idiopathic AA. Certain serologic CMV types have been implicated in transplantation-refractory AA, but these studies have not found application to explain typical AA.48-50 A series of cases clearly attributable to Epstein-Barr virus (EBV) has been described, but again, EBV is a rare cause of AA.51 The best evidence for a viral etiology exists in a specific hepatitis AA syndrome, in which severe AA follows with a 3-6 months latency. So...

Distinct Clinical Entities

AA hepatitis syndrome AA hepatitis syndrome has been described as a rare but instructive variant of this disease clearly pointing to a viral etiology of some cases of AA.52'74 Despite extensive laboratory investigation, such a virus has not been found. It appears that the often fulminant hepatitis initiating the disease is caused by a non-A, non-B, non-C hepatitis virus. The hepatitis is associated with jaundice and an often pronounced rise in transaminases. It can result in fulminant liver failure. In patients who survive the hepatitic phase, transaminases, decrease and a latency period characterized by a period of a relative well-being follows. After a variable time period (often several months), pancytopenia develops with a clinical picture typical of severe AA. ATG therapy is effective and can often result in a complete remission. The time course of the syndrome is highly suggestive of virally induced hepatitis, which upon clearance of virus results in induction of cross-reactive...

Prenatal Evaluation Of The Mother And Fetus

Five of these six had fever plus a prolonged maculopapular rash. Sore throat not associated with painful oral ulcers or reactive cervical lymphadeopathy was also noted. Reactivated HHV-8 infection may also present with symptoms, as evidenced by the case of an immunosuppressed, HHV-8-seropositive adult who developed fever, hepatitis, a maculopapular rash, and pancytopenia secondary to marrow failure in association with detectable HHV-8 DNA in the plasma (62).

Immune allergic drug reactions

Drug-induced hepatitis is rare during therapeutic dosage regimens. Although of unknown aetiology, several features suggest an immunological basis including (i) frequent symptoms of hypersensitivity, with fever, rash and eosinophilia (ii) the presence of specific autoantibodies (iii) liver parenchymal lesions, usually including a mixed cellular infiltrate and (iv) a more rapid and more severe response following rechallenge. Several hundred commonly prescribed drugs are associated with liver toxicity. Berson et al. 7 , reviewing 71 patients treated with 41 different agents, identified no single unifying HLA association. Although none of the individual study groups was of sufficient size for HLA association studies (the maximum was seven patients), a number of interesting observations were reported for individual drugs (Table 16.1), including associations of reactions to tricyclic antidepressants with HLA A11, diclofenac with A11 and chlorpromazine with DR6. In addition, patients with...

Immunogenetic markers as determinants of outcome and fibrogenesis in alcoholic liver disease

Alcoholic liver disease (ALD) progresses to liver cirrhosis in less than 10 of heavy drinkers. This clinical variability, and disappointing results from studies of genes involved in alcohol metabolism, has led to considerations that cirrhosis, fatty liver and alcoholic hepatitis are determined to some degree by genetic factors which regulate the immune system. An immune hypothesis for alcoholic cirrhosis has been suggested, although there is some evidence for a dose response. Twin studies suggest that genes do play a role in determining progression beyond simple alcoholic steatohepatitis, and candidate associations have been sought either with HLA or with other immunoregulatory genes. More recently, attention has focused on the cytokine genes. Ongoing studies at the Centre for Liver Research in Newcastle, UK, have linked TNF-238 and IL-10-627with alcoholic cirrhosis but not with alcoholic hepatitis 36, 37 . The IL-10 gene promoter encodes three SNPs which have been linked with...

Inflammation And Brain Serotonin

As indicated in Section 1, psychopathological symptoms include apathy, agitation, delusions, and depressive symptoms. Depressive symptoms are present in half of patients, and another 25 may suffer delusions. Particularly, agitation and depression are seen in somatic illnesses with inflammatory characteristics (e.g., interferon treatment in hepatitis C, myocardial infarction refs. 103-105). In these psychosomatic disorders, brain serotonin may play a crucial role as for example, selective serotonin uptake inhibitors alleviate concomitant psy-chopathology (106). The cause of these symptoms may in part be explained as the result of awareness of the deteriorating state of patient or by suboptimal functions of, for example, the frontal cortex or parts of the limbic system. The limbic system has classically been associated with mood disorders. In addition, emerging psychopathology may be considered as the direct result of inflammation on brain function, presumably mediated by cytokines...

Eukaryotic Protein Synthesis Is A Little More Complex

How Hepatitis C Takes Control The hepatitis C virus shuts down the liver protein synthesis machinery and forces the resources of the infected cell to be diverted into production of viral proteins that will be used to make new virus. It does this by commandeering the cell's ribosomes to its own mRNAs. Hepatitis C mRNAs do not have a 7-methyl guanosine cap at their 5' ends. Instead they have internal ribosome entry sites (IRES), which are specific sequences to which the ribosomes bind tightly. The clamping of the ribosome to the IRES forces initiation of viral protein synthesis at the expense of host cell protein synthesis. Hepatitis C is a particularly nasty virus because infected people can go on to develop liver cancer, cirrhosis, and other chronic liver disease. In the United States alone, 10,000 people die per year from hepatitis C infection. It is hoped that drugs can be developed that will prevent the host ribosome from binding to the viral IRES and so halt the production of new...

Incidence and aetiology

The single most common cause of ALF is paracetamol intoxication, accounting for 50 of the ALF patients in UK and Denmark and for 20 of ALF patients in the USA. Acute viral hepatitis B is the predominant cause of ALF in central and southern Europe, with acute viral hepatitis E a frequent cause of subacute liver failure in India. Other causes of ALF include mushroom intoxication, drug-induced hepatotoxicity (ecstasy, halothane, valproate and disulfiram), autoimmune hepatitis, cardiac failure, and inherited metabolic diseases.

Aetiology sex and age

In a multivariate statistical analysis of more than 500 patients with ALF, aetiology was found to be the single most important independent predictor of outcome 4 . Fatality rates are invariably 100 in ALF due to Wilson's disease and may exceed 70 in cases due to hepatitis nonA-E and drug-induced liver failure without liver transplantation. In contrast, patients with ALF due to acute viral hepatitis A and B have survival rates of 40-70 . Females with acute fatty liver of pregnancy and patients with paracetamol-induced ALF are those with the best prognosis 3, 4 . Patients aged < 10 years or > 40-50 years show increased mortality from ALF due to hepatitis 1-4 , but gender is of no prognostic value.

Roles of CD8 CTLs in Host Defense

In infections by intracellular microbes, the killing activity of CTLs is important for eradication of the reservoir of infection (see Fig. 10-1B). There are two types of situations in which cells cannot destroy microbes that infect them. First, some viruses live and replicate in cells that are incapable of destroying microbes (such as hepatitis viruses in liver cells). Second, even in phagocytes, some microbes escape from vesicles and live in the cytoplasm, where the microbicidal mechanisms of phagocytes are ineffective because these mechanisms are largely restricted to vesicles (to protect the cells from damage). Such infections can be eliminated only by destroying the infected cells, and in adaptive immune responses, CD8+ CTLs are the principal mechanism for killing infected cells. In addition, the caspases that are activated in target cells by granzymes and FasL cleave many substrates and activate enzymes that degrade DNA, but they do not distinguish between host and microbial...

Literary Analysis

Pants were intentionally infected with syphilis, promulgating notions of genocide. In a concomitant study also in direct defiance of the Nuremberg Code, at the infamous Willowbrook State School in New York from 1955 through the early 1970s newly admitted mentally retarded children were deliberately infected with hepatitis to study the course of the disease. Their parents were told it was a condition of admission and that their children would get it anyway. In this instance and in other studies of infectious diseases, live cancer, and radiation, scientific fervor took precedence over basic human rights, turning what should be autonomous human beings into scientific sacrifices. TSS folklore passed down through generations explains the distrust of white medicine, creating a health gap. By 2010 a new government initiative, Eliminating Racial and Ethnic Disparities in Health, hopes to end the practice of lower minority medical standards in six priority areas infant mortality, cancer...

Prognosis by diagnosis

The natural course of hepatic disorders is determined by age, gender, the type of the disorder and its biological activity. The resulting prognosis is greatly variable, as shown in Table 20.1. The worst prognosis is observed in paediatric liver diseases such as extrahepatic biliary atresia 2 , and some transporter defects 3 , and hepatic metabolic disorders 1 . The later the manifestation of a hepatic disorder, the longer its natural course will be. In general, chronic end-stage liver disease in PBC, PSC or hepatitis B and C is only observed after 10-20 years 4, 5 . In acute liver failure, both children and adults have a poor prognosis of only a few days. In both age groups, the absolute prothrombin time (PT) or its international normalized equivalent (INR) have been shown to be the best prognostic predictors a PT result below 20 of normal indicating almost no chance of spontaneous survival (Table 20.1) 11 .

Risk Of Fetal And Neonatal Infection

Maternally derived neutralizing antibody does not necessarily protect against neonatal infection, although it does provide some protection against neonatal EV disease. Conversely, absence of or low neutralizing titer to an infecting EV serotype is a significant risk factor for development of symptomatic infection (38,72,73,84). Route of delivery has not been demonstrated to affect the incidence or severity of neonatal EV disease cases following cesarean section are described (3,34,38,72). Factors that are associated with severe neonatal disease include maternal illness prior to or at delivery, prematurity, early age of onset of illness (especially the first few days of life), multiorgan disease, severe hepatitis hepatic necrosis, positive serum viral culture, specific infecting serotypes (e.g., group B coxsackieviruses and echovirus 11), and lack of neutralizing antibody to the infecting serotype (32-34,36-38,84,85).

Philip Bialer Rosalind G Hoffman and Jeffrey Ditzell

Hepatitis C virus (HCV) coinfection has also become a major problem among those with HIV. Of persons injecting drugs for at least 5 years, 60 to 80 are infected with HCV (CDC, 2002). In China, 95 of HIV-positive heroin users were also infected with HCV (Garten et al., 2005). The sharing of contaminated needles can lead to multiple medical problems including skin infections, endocarditis, septicemia, and pulmonary emboli.

Total Pathogen Burden As An Aggregate Serological Risk Factor

Graph of adjusted death MI HRs based on baseline IgG seropositivity to number of pathogens (pathogen burden), including CMV, hepatitis A virus, HSV-1, HSV-2, C.pneumoniae, and H. pylori among 890 patients with significant CAD on angiography who were followed for 3 yr(96). Fig. 7. Graph of adjusted death MI HRs based on baseline IgG seropositivity to number of pathogens (pathogen burden), including CMV, hepatitis A virus, HSV-1, HSV-2, C.pneumoniae, and H. pylori among 890 patients with significant CAD on angiography who were followed for 3 yr(96).

Initial Evaluation Of The Patient With Substance Use Disorders

Early in the epidemic, heroin addiction led to a rapid spread of HIV and HCV among IDUs in the United States, since few addicts had access to clean needles and syringes. The increase in the purity and availability of heroin along with a decrease in its street price has led to a resurgence in the use of heroin over the past 15 years. There are 600,000 to 800,000 heroin addicts in the United States however, less than 20 are currently in treatment for their addiction (Community Epidemiologic Work Group, 2000).

Evaluation Of The Neonate

If a newborn appears ill or if there are findings suggestive of hepatic involvement (e.g., hepatomegaly or jaundice) or bleeding, liver function tests should be obtained. Transaminase elevation or increased bilirubin suggests the presence of hepatitis. Ammonia levels may need to be monitored in the presence of severe hepatic involvement, especially if profound lethargy is present. In an infant with hepatitis or evidence of bleeding or in any newborn who appears clinically ill, the platelet count and coagulation profile should be monitored. A chest radiograph is indicated in the presence of respiratory or cardiac symptoms. Infiltrates may indicate pneumonia or heart failure, and cardiac enlargement suggests myocarditis or pericarditis.

Interpretation Of Diagnostic Evaluations

The primary causes of neonatal EV infections are the coxsackie B viruses and the echoviruses coxsackie A viruses are implicated less often (37). An association has been observed between EV subgroup and disease pattern, with coxsackie B viruses associated with meningoencephalitis and myocarditis and echoviruses associated with hepatitis and coagulopathy, but significant overlap exists (34,36,38). Coxsackie B virus-associated hepatitis and coagulopathy have been increasingly reported (99). Coxsackieviruses B2-B5 and echoviruses 6, 11, and 19 are frequently the causes of severe neonatal disease (34,36-38). Many other EV serotypes have also been reported to cause severe neonatal disease, however. In the absence of an epidemic situation or the occurrence of a unique disease manifestation, identification of the EV subgroup and serotype is generally not necessary and does not have an impact on clinical management.

Historical Context

Saying You're either on the bus or you're off the bus was Beat Generation lingo for creative tripping. The exploits of the Pranksters are the subject of Tom Wolfe's The Electric Kool-Aid Acid Test (1968), a book voraciously consumed by antiestablishment hippies in search of the universe within. Kesey went on to write other novels, but none achieved the success of Cuckoo's Nest, which subsequently influenced popular culture with its stage and film productions. Late in life, Kesey, the pied piper of the psychedelic era, took drugs only for his diabetes and hepatitis C, finding the pure adrenaline of experiencing nature enough. He died on November 10, 2001, in Pleasant Hill, Oregon, following surgery for liver cancer.

Kava Piper methysticum

Kava is an herb native to the South Seas, where it is valued for its calming and sedative properties. Double-blind studies in humans have shown efficacy for treating anxiety (8). Kava also appears to have analgesic, muscle-relaxing, and anticonvulsant effects, though these have not been scientifically proven in humans. The anticonvulsant potential of kava may be mediated via an enhancement of GABA within the brain, or possibly via blockade of sodium and calcium channels, similar to the actions of several standard AEDs (8). Rare instances of abnormal movements, acute hepatitis, liver failure, and rash (8) have been reported with kava. This herb is contraindicated in depressed patients because the danger of suicide may be increased (8).

Genetic abnormalities

Association with infectious agents Despite relevant geographic variations, hepatitis C virus (HCV) seems to be involved in splenic MZL and nodal MZL lymphomagenesis.97-101 Of great interest, some patients with splenic lymphoma with villous lym-phocyes and HCV infection achieved a lymphoma remission after treatment with interferon alfa with or without concomitant ribavirin.101102 This suggests a strict relationship between HCV and splenic MZL, indicating the necessity to search for HCV infection in patients affected by this lymphoma subtype. Analogous to the H. Pylori infection in the gastric MZL, it appears that HCV may be responsible for an antigen-driven stimulation of the lymphoma clone. Prospective studies are warranted to confirm this interesting finding.

Stephen L Dilts Jr Stephen L Dilts

The history of opioid use goes back thousands of years in human history. The Ebers Papyri from approximately 7000 B.C. refer to the use of opium in children suffering from colic (Deneau & Mule, 1981). In the Victorian era, the use of laudanum was socially acceptable. In the present day, opioids use is stringently regulated, especially in the United States however, demand by addicts results in the existence of a black market characterized by crime, disease, poverty, and loss of personal and social productivity. The sexually promiscuous intravenous heroin user is at high risk to contract and effectively spread the deadly acquired immune deficiency syndrome (AIDS) virus, as well as venereal and other infectious diseases, such as hepatitis C. High overall death rates are associated with opioid abuse, approximately 10-15 per 1,000 in the United States (Jaffe, 1989). The Drug Abuse Warning Network (Substance Abuse and Mental Health Services Administration, 1995) indicates an alarming...

Detection Methods For Viralload Assessment

CE has since been used successfully in the research setting to separate and quantitate PCR products of HIV-1, HBV, CMV, and HCV (35-39). The introduction of CE with LIF and intercalating dyes improved detectability to the attomole level with sample volumes as little as a few picoliters (4043). CE represents a safe and automatable assay system for quantitative analysis and routine laboratory analysis may soon be the norm. With current CE-LIF technology, samples are analyzed individually (52). Each sample usually has a 15-45 min run time, whereas multiple samples can be analyzed simultaneously by SGE. For analysis of a single sample, CE-LIF may be faster, but when multiple analyses are required, SGE may be more time efficient. With the multicapillary instruments currently under development, analysis of multiple samples simultaneously by CE-LIF will be possible. In addition to requiring a longer time, individual sample processing also means that each sample is analyzed separately...

AntiCD137 mAbs Disrupt Hematopoiesis in Mice

We have found that repeated anti-CD137 treated lupus prone NZB W F1 mice develop multi-focal hepatitis. Cessation of anti-CD137 treatment led to the resolution of hepatitis. To determine whether development of hepatitis was or was not related to the susceptibility of NZB W F1 mice to autoimmune disease, we repeatedly injected normal naive mice with therapeutic doses of anti-CD137. Like NZB W F1 mice, we found that normal mice also developed hepatitis. Further

Major Depressive Disorder

Rates of major depression range from 8 to 67 (Acuff et al., 1999) however, up to 85 of HIVseropositive individuals report the prevalence ofsome depressive symptoms (Tate et al., 2003) that may not reach diagnostic threshold for a major depressive disorder diagnosis. Examples would include minor depressions and dysthymia. This may especially be true when taking into account the prevalence of depression in other medical illnesses that are comorbid with HIV, including HCV, end-stage renal disease, diabetes mellitus, and other endocrinopathies. Indeed, the impact of HIV disease on mental health was illustrated by a meta-analysis by Ciesla and Roberts (2001), who found that HIV-infected patients were almost twice as likely to be diagnosed with major depressive illness, irregardless of the symptomatic status of their HIVdisease.Theprevalenceand epidemiology of mood disorders are covered more extensively in Chapter 4 of this text. Valproate in patients with hepatitis C coinfection deserves...

Classification of Diabetes Mellitus and the Metabolic Syndrome

Immune-mediated diabetes, previously referred to as insulin-dependent diabetes, type I diabetes, and juvenile-onset diabetes, accounts for 5-10 of all cases of diabetes. Immune-mediated diabetes typically develops in childhood and adolescence, but has a variable age of onset ranging from infancy to the eighth and ninth decades of life. Abnormalities in glucose homeostasis result from severe insulin deficiency due to cell-mediated autoimmune inflammation (insulitis) and subsequent destruction of the b-cells of the pancreas. In T1DM, daily exogenous insulin administration is a life-sustaining intervention, and the absence of insulin can result in a state of acute metabolic decompensation known as diabetic ketoacidosis (DKA). Individuals with T1DM are at increased risk for other autoimmune disorders such as Graves' disease, Hashimoto's thyroiditis, Addison's disease, vitiligo, celiac sprue, autoimmune hepatitis, myasthenia gravis, and pernicious anemia.

Formulation of Guidelines

This information can help to allay unnecessary anxiety from the outset and ensures that the victim is referred, if appropriate, to the designated hospital at the earliest opportunity. Knowledge of precise treatment protocols is not required, but it is helpful to be able to explain to the victim what to expect. For example, he or she will be asked to provide a voluntary baseline blood sample for storage and numerous follow-up samples for testing depending on the nature of the exposure. This is especially relevant for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Occasionally, it may be necessary for samples to be obtained as long as 6 mo after the incident.

Less Enzyme Or Defective Protein

Isoniazid-induced neurotoxicity Drug-induced lupus erythematosus Phenytoin-isoniazid interaction Isoniazid-induced hepatitis Arylamine-induced bladder cancer Increased susceptibility to drug-induced hemolysis Glucose-6-phosphate dehydrogenase deficiency Other defects in glutathione formation or use Hemoglobinopathies Hereditary methemoglobinemia Hypoxanthine-guanine phosphoribosymtransferase-

Symptoms and Complications

Prevalence of Chronic Hepatitis B HBsAg, hepatitis B surface antigen HbeAg, hepatitis B e antigen HbeA, hepatitis B e antibody HBCA, hepatitis B core antibody HBSA, hepatitis B surface antibody. HBsAg, hepatitis B surface antigen HbeAg, hepatitis B e antigen HbeA, hepatitis B e antibody HBCA, hepatitis B core antibody HBSA, hepatitis B surface antibody.

Stephen J Ferrando and Constantine G Lyketsos

The landscape changed with the advent and widespread use of HAART in the mid-1990s. The incidence of HAD has declined (Sacktor et al., 2001a), but, since patients live longer, these disorders may have a stable or increasing prevalence. Further, milder forms of impairment persist in a substantial proportion of patients (Ferrando et al., 1998 Starace et al., 2002), with higher levels of immune functioning (Dore et al., 1999), and the course is highly variable, including fluctuation over time, progression, or even regression of the symptoms. Motor manifestations, while continuing to occur in some cases, are less frequent. Finally, comorbid and differential diagnostic considerations for the cause of these disturbances have shifted away from opportunistic infections toward entities such as substance abuse, hepatitis C coinfection, and the neu-ropsychiatric and metabolic side effects of antiretro-viral medications. To account for these shifts, the diagnostic criteria for HIV-associated...

Inhibitory Nk Receptors

A similar phenomenon is also seen with the tetraspanin CD81, which specifically binds to hepatitis C virus envelope glyco-protein E2 (Crotta et al, 2006). NK cells express CD81, and its cross-linking blocks CD16 and IL-12-induced NK cell activation against tumor cells. NKG2D-mediated lysis was also reduced by CD81 ligation. Thus, both B7-H3 and CD81 receptor types can inhibit the activation signal in NK cells.

Epidemiology and Prevalence

HCV is endemic in most parts of the world. Approximately 3 (200 million) of the world's population is infected with HCV (15). For many countries, no reliable prevalence data exist. Intermediate prevalence (1-5 ) exists in Eastern Europe, the Mediterranean, the Middle East, the Indian subcontinent, and parts of Africa and Asia. In Western Europe, most of Central America, Australia, and limited regions in Africa, including South Africa, the prevalence is low (0.2-0.5 ). Previously, America was included in the low prevalence group, but a report published in 2003 (17) indicated that almost 4 million Americans (i.e., 1.8 of the population) have antibody to HCV, representing either ongoing or previous infection. It also states that HCV accounts for approx 15 of acute viral hepatitis in America. Hepatitis B vaccine GP, Family doctor HBsAg, hepatitis B surface antigen AS, accelerated schedule RDS, rapid schedule HBSIG, hepatitis B-specific immunoglobulin. GP, Family doctor HBsAg, hepatitis B...

Routes of Transmission

Approximately 75 of cases are parenteral (e.g., needle-stick, etc.) (19). Transmission through the sexual route is not common and only appears to be significant if there is repeated exposure with one or more people infected with HCV. Mother-to-baby transmission is considered to be uncommon but has been reported (20). Theoretically, household spread is also possible through sharing contaminated toothbrushes or razors. is contained within the document Hepatitis C Strategy for England, issued by the UK Department of Health in 2002 (18).

Management in Custody

Hepatitis D (A Agent) HDV is associated with acute (coinfection) and chronic hepatitis (superinfection) and can exacerbate pre-existing liver damage caused by HBV. The routes of transmission and at-risk groups are the same as for HBV. Staff victims in contact with a putative exposure and detainees with disease should be managed as for HBV. Interferon-a (e.g., Roferon) can be used to treat patients with chronic HBV and HDV (21), although it would not be practical to continue this treatment in the custodial setting.

Differential Diagnosis

Hepatitis C infection, independent of HIV coin-fection and interferon ribavirin therapy, is characterized by multiple neuropsychiatric complaints, most frequently fatigue (up to 97 of patients), depression (up to 25 of patients meet criteria for a current depressive disorder and up to 70 have elevated scores on depression rating scales), and cognitive dysfunction (up to 82 impairment on some measures) (Crone and Gabriel, 2003). Compared to patients with HIV alone, patients with comorbid HIV and hepatitis C are more likely to have disturbances in executive function and dementia (Ryan et al., 2004). The pattern of cognitive impairment associated with hepatitis C is similar to that of HIV. Patients with mild liver disease tend to have impairment in attention and concentration, and patients with more severe liver fibrosis have problems with learning, psychomotor speed, and cognitive flexibility. Patients with end-stage liver disease and cirrhosis experience superimposed delirium (hepatic...

Of Staff Victims in Contact With Disease

Management in custody of staff victims in contact with disease includes following the immediate management flow chart (Fig. 1) and contacting the designated hospital specialist with details of the exposure. Where possible, obtain a blood sample from the contact. Regarding HBV and HCV blood samples in the United Kingdom, they can only be taken with informed consent. There is no need for the forensic physician to go into details about the meaning of the test, but the contact should be encouraged to attend the genitourinary department (or similar) of the designated hospital to discuss the test results. Should the contact refuse to provide a blood sample, then any information about his or her lifestyle, ethnic origin, state of health, etc., may be useful for the specialist to decide whether postexposure prophylaxis (PEP) should be given to the victim. Where only saliva is involved in a penetrating

Adaptive Immunity to Viruses

Lymphocytic choriomeningitis virus (LCMV) infection in mice, which induces inflammation of the spinal cord meninges. LCMV infects meningeal cells, but it is noncy-topathic and does not injure the infected cells directly. The virus stimulates the development of virus-specific CTLs that kill infected meningeal cells during a physiologic attempt to eradicate the infection. Therefore, meningitis develops in normal mice with intact immune systems, but T cell-deficient mice do not develop disease and instead become carriers of the virus. This observation appears to contradict the usual situation, in which immu-nodeficient individuals are more susceptible to infectious diseases than normal individuals are. Hepatitis B virus infection in humans shows some similarities to murine LCMV in that immunodeficient persons who become infected do not develop the disease but become carriers who can transmit the infection to otherwise healthy persons. The livers of patients with acute and chronic active...

Clinical Features

The disease is transmitted as an autosomal recessive trait and can occur from childhood through adolescence. Cardinal clinical manifestations are hepatic, neurologic, and psychiatric. Acute or chronic hepatitis and liver cirrhosis are common. During the course of the disease, splenomegaly, kidney dysfunction, and clotting abnormalities develop.

Synthetic Antigen Vaccines

A goal of vaccine research has been to identify the most immunogenic microbial antigens or epitopes, to synthesize these in the laboratory, and to use the synthetic antigens as vaccines. It is possible to deduce the protein sequences of microbial antigens from nucleotide sequence data and to prepare large quantities of proteins by recombinant DNA technology. Vaccines made of recombinant DNA-derived antigens are now in use for hepatitis virus, herpes simplex virus, foot-and-mouth disease virus (a major pathogen for livestock), human papillomavirus, and rotavirus. In the case of the most widely used human papillomavirus vaccine, recombinant viral proteins from four viral strains (HPV 6, 11, 16, and 18) are made in yeast and combined with an adjuvant. HPV 6 and 11 are common causes of warts, and HPV 16 and 18 are the most common HPV strains linked to cervical cancer. This antiviral vaccine is therefore also a preventive cancer vaccine.

Host Defense and Viral Infection Mechanisms

Hepatitis C virus (HCV) is the major cause of posttransfusion and community-acquired hepatitis in the world. The majority of HCV-infected individuals develop chronic hepatitis that may progress to liver cirrhosis and hepatocellular carcinoma. The HCV structural proteins comprise the core protein and the two envelope glyco-proteins E1 and E2 (43). Several lines of evidence have demonstrated that the HCV envelope proteins may play a crucial role in the initiation of infection by mediating virus-host cell membrane interaction. E2 is thought to initiate viral attachment, whereas E1 may be involved in virus-cell membrane fusion (44-46). A comparative structural analysis of the E2 protein of various HCV isolates demonstrated that positively charged amino acid residues are highly conserved in the N-terminus of E2 hypervariable region 1 (47), thereby suggesting the negatively charged cell surface GAG, heparan sulfate, as an HCV receptor. Heparin directly interacts with E2 and binding of E2 is...

Transmission of Infectious Agents

Exposure to Infected Body Fluids As you learned in Chapter 9, AIDS is caused by exposure to infected blood. Hepatitis is another disease caused by contact with infected blood. There are at least six different hepatitis viruses, but the most dangerous is the virus known as hepatitis C. Exposure to hepatitis C leads to chronic liver diseases such as cirrhosis (irreversible, potentially fatal scarring of the liver), liver cancer, and liver failure. Hepatitis C ranks second to alcoholism as a major cause of liver disease and is the leading reason for liver transplants in the United States.

Julia Skapik Alexander Thompson Andrew Angelino and Glenn Treisman

The cost of untreated psychiatric illness includes disability, increased medical expenditure, and societal costs such as crime and increased transmission of communicable diseases such as HIV and hepatitis B and C. The potential benefits of preventing crime and HIV transmission, and reducing disability far outweigh the added costs of treatment. The addition of psychiatric services to existing HIV AIDS clinics can cost as little as a few hundred dollars per week and can prevent emergence of multidrug-resistant viral strains through improved adherence, decrease HIV transmission by reduction in risk behaviors, and decrease disability in patients.

Medical Complications Direct Results of Cocaine

Complications of intravenous cocaine use are multiple and include skin abscesses, phlebitis and cellulitis, and septic emboli resulting in pneumonia, pulmonary abscesses, subacute bacterial endocarditis, ophthalmological infections, and fungal cerebritis (Wetti, Weiss, Cleary, & Gyori, 1984). Injected talcandsili-cate may cause granulomatous pneumonitis with pulmonary hypertension, as well as granulomata of the liver, brain, or eyes (Estroff & Gold, 1986). Hepatitis B, hepatitis C, and delta agent are all too frequently by-products of intravenous drug abuse. In the past several years, concomitant with the increase in HIV infection, there has been an increase in pneumonia, endocarditis, tuberculosis, and hepatitis delta and other sexually transmitted diseases in drug users (see Chapter 19 on HIV and addictions for more information on cocaine and HIV AIDS).

Medical Management Of Individuals With Severe Mental Illness

It is therefore necessary to aggressively screen individuals with mental illness for both HIV and other medical illnesses, such as diabetes, hepatitis, hypertension, and heart disease. It is helpful for both patients and providers to centralize care as much as possible, making all providers aware of all medical problems as well as the current treatment plan to provide a consistent message (Treisman and Angelino, 2004). Frequent pregnancy testing and on-site prenatal care may improve outcomes for pregnant women with HIV. It is important to incorporate preventative medicine whenever possible, including smoking cessation, weight management, and risk reduction this counseling has been often overlooked in patients with multiple medical problems and with HIV, but is even more crucial now that HIV AIDS has become a chronic illness. We emphasize that psychiatric providers should be vigilant about screening for medical illnesses, even using a standard medical review questionnaire for the...

Pylori A Type I Carcinogen

Several diverse malignancies are known to arise from a background of chronic inflammation. Cholangiocarcinoma and bladder cancer are strongly associated with infection with the Digeneans Opisthorchis sinensis and Schistosoma haematobium. The viral infections hepatitis B and C and human papillomavirus have been causally linked with hepatocellular carcinoma and cervical carcinoma. H. pylori is the first bacterium to be linked with the development of human neoplasia. Prospective epidemiologic stud-

Cancer Prevention Trials with Selenium

From the 1980s onward, several cancer prevention trials with selenium have been conducted. The first trial which showed a protective effect of selenium A was performed from 1985-1989 in Qidong, a region north of Shanghai with a high incidence of primary liver cancer (PLC) and hepatitis B (HB) (33-35). Subjects in one commune in the center of the endemic area receiving table salt fortified with sodium selenite experienced a drop of PLC and HB incidence to approximately one-half of the incidences observed in control populations maintained on ordinary salt. Another intervention trial was conducted from 1984 to 1991 in Linxian, Hen-an Province, China, a region with high incidence of esophageal cancer (36). In this trial the cancer protective effects of several vitamins and minerals including selenium were tested against a placebo. While supplemental retinol, zinc, riboflavin, niacin, molybdenum, and vitamin C were ineffective, supplemental selenium combined with p-carotene and vitamin E...

Antigens of Oncogenic Viruses

The realization that immune responses against viruses protect individuals from virus-induced cancers has led to the development of vaccines against oncogenic viruses. For example, a vaccine against HPV is now in use, which has the potential to reduce the incidence of cervical cancer in women. The vaccine is composed of recombinant HPV capsid proteins from the most common onco-genic strains of HPV, which form virus-like particles free of viral genome. Vaccination against hepatitis B virus is also reducing the incidence of liver cancer. In this case, the virus is not oncogenic, but it promotes the development of liver cancer probably by inducing chronic inflammation, which is a risk factor for cancer development (discussed later in the chapter).

Primeboost Strategies In Cancer Immunotherapy

Immunization has traditionally relied on repeated administration of antigen to augment the magnitude of the immune response. With the advancement in recombinant DNA technology, genetically engineered vaccines such as expression plasmids, recombinant proteins, viruses, and bacteria have become the latest modalities for vaccine development. The first such vaccine in its class, a hepatitis B virus vaccine in the form of recombinant protein produced in yeast, has been shown to be potent in providing protective efficacy in humans (43,44). While this homologous protein-based immunization is very effective for generating humoral immune responses, it is generally inefficient in inducing cell-mediated immunity important for protection against infections caused by intracellular pathogens and for cancer immunotherapy. DNA vaccines, on the other hand, have been tested in small and large animal models, and have demonstrated efficacy in inducing both humoral and cellular immunity for infectious...

Clinical Reminders and Alerts

The clinical reminder system exists to improve preventive health care and to encourage timely clinical interventions to be initiated. Reminders may be viewed on the cover sheet and also during the writing of progress notes. They alert the clinician to certain actions that should be performed. Examples of these actions include examinations, immunizations, patient education, and laboratory tests. Reminders assist in identifying patients who are at risk for hepatitis C, breast cancer, colorectal cancer, hypertension, etc. Some of the actions a clinician may take upon receipt of a reminder include performing an examination, ordering a test, or collecting specific patient information. The information collected in response to a clinical reminder may be automatically appended to the current progress note. Figure 15.4 shows the clinical reminder dialogue that is displayed when tobacco screening is due.

Gastrointestinal Function

Viral hepatitis, most often related to transfusion of blood products prior to 1992, is another cause of chronic liver disease in long-term survivors 110-112 . In one retrospective series of 658 cancer survivors who had been treated before routine screening of blood products, 117 (17.8 ) were seropositive for hepatitis C 111 35 of these also were positive for hepatitis B with or without delta virus. Eighty percent of the seropositive patients had been transfused, so that in 20 other risk factors appeared to have been responsible. In one series of 10-year survivors of bone marrow transplantation for hematologic malignancy, hepatitis C was the major risk factor for late development of cirrhosis of 16 patients with cirrhosis, 15 had disease attributable to hepatitis C 113 . Hepatitis B has largely been eliminated in populations treated after 1972 The true incidence of hepatic pathology is undoubtedly higher than current numbers suggest because the presence of cirrhosis is seldom reflected...

The Role Of The Immune System In Promoting Tumor Growth

Although much of the emphasis in tumor immunology has been on the role of the immune system in eradicating tumors, it is clear that the immune system may also contribute to the development of some solid tumors. In fact, chronic inflammation has long been recognized as a risk factor for development of tumors in many different tissues, especially those affected by chronic inflammatory diseases such as Barrett's esophagus, Crohn's disease, pancreatitis, and prostatitis, for example. Some cancers associated with infections are also considered to be an indirect result of the carcinogenic effects of the chronic inflammatory states that are induced by the infectious organisms. These include gastric cancer in the setting of chronic Helicobacter pylori infection and hepatocellular carcinomas associated with chronic hepatitis B and C virus infections. Although the mechanisms by which chronic inflammation can promote tumor development are not well understood, there are several possibilities,...

Causes And Mechanisms Of Immune Activation In Hiv Infection

Independently of the effect of HIV viral gene products, another important cause of immune activation stems from co-infections with non-HIV pathogens. In many regions of the world, the co-infection of HIV-infected patients with other pathogens is highly prevalent, and these co-infections often persist as chronic and recurrent acute infections. Common co-infections17,18 include protozoan parasites (e.g., Leishmania donovani, Toxoplasma gondii, Plasmodium falciparum) and bacteria (e.g., Mycobacterium sp. and Neisseria gonorrhea). Co-infections with viruses such as human herpesvirus (HHV)-6, human simplex virus (HSV)-1, cytomegalovirus, and hepatitis B and C viruses are also prevalent worldwide. Certain co-infections, in particular, parasitic infections, are believed to contribute significantly to HIV-associated morbidity and mortality by a mechanism of microbial-induced immune activation and its consequences. The mechanism of immune activation in these situations has been attributed to...

Infectious Complications

Results from a phase I trial demonstrated that IVIG could be safely given to patients with MM.40 Seventeen patients were given doses of IVIG ranging from 150 mg kg to 500 mg kg. The infusions were well tolerated, with no significant toxicities. The investigators measured functional antibody to hepatitis B surface antigen and found a range in the half-life from 7 to 20 days for the entire group.40 The kinetics of the antibody did not appear to be related to the M-protein subtype or baseline native immunoglobulin G (IgG) levels.40

Electroencephalographs Studies of Chronic Substance Abusers

Hepatitis, cardiovascular disorders, diabetes, HIV AIDS, malnutrition), licit and illicit medication use, head injuries, seizures, and epilepsy (Lowinson et al., 1992). In addition, substance dependent patients exhibit low levels of compliance motivation, below average IQ scores, and higher-than-normal rates of childhood psychopathology. Other complicating factors include dysfunctional environmental or genetic histories, and educational, social, or cultural factors (e.g., reading disability or illiteracy, language barriers, a below-average level of educational achievement that is overestimated by educational attainment) all of which predate their substance abuse careers. The simple demonstration of a difference in EEG EP ERP (or other neuroimag-ing) indices between a group of patients and a group of healthy volunteers is therefore insufficient for inferring causation, unless the researchers have either matched the groups on all of these potential confounds, excluded all patients with...

Risk Based Healthcare of Survivors

Faced with these risks and challenges, how can the healthcare delivered to survivors be optimized It is important to recognize that there is a window of opportunity to modify the severity of health outcomes by prevention or early intervention. Early diagnosis and intervention or preventive care targeted at reducing risk for late effects can benefit the health and quality of life of survivors 6 . The outcomes of the following late effects can be influenced by early diagnosis and early intervention second malignant neoplasms following radiation therapy (breast, thyroid, and skin), altered bone metabolism and osteoporosis, obesity-related health problems (dyslipidemia, hypertension, diabetes mellitus, cardiovascular disease), liver failure secondary to chronic hepatitis C following blood transfusion, and endocrine dysfunction following chest mantle or cranial radiotherapy. Primary, secondary, and tertiary prevention, including tobacco avoidance cessation, physical activity, low-fat diet,...

Markers of chronic allograft rejection

Since early chronic rejection can be treated, differential diagnosis is crucial. Chronic rejection is usually not difficult to recognize on the basis of the histopath-ological findings, but establishing the diagnosis with certainty often requires a thorough review of previous biopsies, which usually show acute rejection with significant bile duct damage. The major problem areas are distinguishing (i) early chronic rejection from a normal or near normal biopsy (ii) early chronic rejection from chronic hepatitis with bile duct damage and (iii) whether chronic rejection or some other insult is responsible for the ductopenia or perivenular fibrosis, if present. Liver function tests are probably most helpful in the first problem area and selective elevation of the 'canalicular' enzyme, alkaline phosphatase, in an otherwise healthy long-term liver allograft survivor should prompt the pathologist to look more closely at the integrity of the bile ducts and the number of portal tracts sampled....

Utility of Long Range PCR

Recent development of a long range reverse transcriptase PCR (RT-PCR) system has extended the scope for assaying for rare transcripts and tissue specific gene expression. Amplifications of full length transcripts of hepatitis A virus (12) and transcripts as large as 13.5 kb has recently been demonstrated. Long range PCR has also impacted on the differential display technique, allowing larger transcripts to be studied (13).

Drugs Targeting Reverse Transcriptase

The latest of the currently approved nucleoside inhibitors of RT is lami-vudine (3TC 3'-thio-2',3'-dideoxcytidine, Epivir), which was discovered by Bio-Chem Pharma and developed by Glaxo-Wellcome. It gained FDA approval in 1995. In addition to being a potent AIDS drug, lamivudine has also been shown to be potent against another viral disease, chronic hepatitis B. Since lamivudine has been shown to elicit very rapid resistance (see below), its initial development was questionable. However, after it was found that the principal mutation due to the exposure to lamivudine, M184V, prevents resistance to zidovudine, a combination of both drugs (Combivir, which consists of 150 mg of lamivudine combined with 300 mg of zidovudine) was developed.

Risk Factors and Etiology

HCCs appear to result from complications of previous hepatic damage due to metabolic or inflammatory disorders. Chronic infection with hepatitis B virus is the leading cause of HCC in children, adolescents, and young adults in Asia and Africa. However, in the Western countries, less than one-third of the adolescent or young adult patients diagnosed with HCC have an identifying cause such as hepatitis or other inflammatory liver disease 4, 5 . This is in marked contrast to older adults, in whom almost 90 of the cases are cirrhosis related, secondary to viral infection or alcohol consumption 6 . The prevention of a carrier state in children by a universal program of hepatitis B immunization has shown a dramatic decrease in the preva lence of chronic hepatitis B virus, and a decline in the rates of HCC in Taiwan among children less then 15 years of age 7 .

Should Nature Be Patented

To be patented, the invention in question must be new, useful, and not already known to the public. For example, if scientists discover a new gene in the human body, they cannot patent it in its natural state. They can patent a gene, however, if they are the first to isolate it and identify a use for it, such as producing a protein medicine. One example of this is interferon, a protein that helps regulate the immune system and helps stop viruses (tiny organisms that can cause disease). Interferon has been patented for preventing and treating diseases such as leukemia (a cancer that affects the blood-forming cells in bone marrow) and hepatitis C (a disease of the liver).

Genetic and Molecular Mechanisms of Hepatocarcinogenesis

Recent publications have summarized the vast data now available on the genetic and molecular pathogenesis of human HCCs 36, 44, 45 . Briefly, the development of HCC is a slow, multistep process that is associated with changes in genomic expression that lead to alterations of the hepatocellular phenotype and the appearance and progression of a tumor. The development of HCC may take many years, and starts in the setting of chronic hepatitis or cirrhosis, with destruction of hepatocytes and inflammatory changes that alter the matrix and the microenvironment of the liver.

Clinical Presentation and Diagnosis

Levels of carcinoembryonic antigen and ferritin can also been increased in HCC 48 . The fibrola-mellar variant of HCC can be associated with an abnormality of the vitamin B12 binding protein, which can occasionally be used to monitor disease status and response to therapy 25, 48 . Screening for viral hepatitis (B and C) should be performed in all patients.

Clinical Disease Manifestations Of Hivassociated Cognitive Impairments

May present with a mild influenza-like illness and rarely a mononucleosis-like syndrome (Martin et al., 1992 Beckett and Forstein, 1993 Huang et al., 2005). A portion of these individuals will develop headaches, fever, myalgia, anorexia, rash, and or diarrhea within the first 2 weeks (Schacker et al., 1996 Lindback et al., 2000 Tyrer et al., 2003 Pilcher et al., 2004). Prior to seroconversion, the acute phase of viral infection is characterized by a rapid HIV-mediated loss of memory CD4+CCR5+ T cells within the mucosal tissues that results in potentially irreversible immune suppression (Veazey et al., 1998 Brenchley et al., 2004 Mehandru et al., 2004 Derdeyn and Silvestri, 2005). During this acute HIV infection, high levels of vire-mia and viral shedding at mucosal sites occur. Genital and oral ulcers, cancers, and coinfections with a number of sexually transmitted microbial pathogens, including herpes simplex and hepatitis viruses, syphilis, and gonorrhea, can also manifest during...

CD137CD137 Ligand in the Antiviral Immune Response and in Viral Vaccination

Immunotherapy has potential for chronic and latent viral infections. Therapeutic vaccination and adoptive T-cell transfer are the strategies that are being explored for HIV and chronic viral hepatitis. Mice lacking CD137 or CD137 ligand show defects in CD8 T cell responses against viruses (DeBenedette et al., The induction of protective or therapeutic cellular immunity against hepatitis C virus (HCV) is a difficult goal. Immunization with a recombinant aden-ovirus encoding HCV-NS3 (RAdNS3) could partially protect mice from challenge with a vaccinia virus encoding HCV antigens. It was found that treatment with anti-CD137 mAb after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T helper cell responses against HCV NS3 (Arribillaga et al., 2005). Importantly, the ability of RAdNS3 to induce protective immunity against challenge with a recombinant vaccinia virus expressing HCV proteins was markedly augmented. Thus, combination of immunostimulatory anti-CD137 mAb...

Cancer Is a Global Problem

Ences among developing and developed countries in the incidence rates of certain cancers, lung cancer is the most common cancer among men in both regions of the world and breast cancer is the most common cancer in women (Fig. 3-4).5 There are, however, regional differences in the distribution of various cancers in different regions of the world that reflect differing etiologic factors. For example, infectious etiology plays a greater role in certain parts of the world, e.g., the role of schistosomiasis infections in causing bladder cancer in parts of Africa and that of hepatitis B infections in liver cancer in China

Acquired Generalised Lipodystrophy Lipoatrophic Diabetes or Lawrence Syndrome

Acquired generalised lipodystrophy (AGLD) is a rare, juvenile-onset lipodystrophy, first fully described by Lawrence in 1946 1 , who reported on a young female subject with 'lipodystrophy, and hepatomegaly with diabetes, lipaemia and other metabolic disturbances.' To date, approximately 80 patients with AGLD have been reported 2 . Like others LDs, AGLD is prevalent in females. Lipoatrophy develops over a number of years, in childhood or in adolescence, so that the onset of the condition is later than that of congenital generalised lipodystrophy (CGLD). Extended areas of subcutaneous fat are involved, including the face, arms, and legs. Less frequently mesenteric, retroperitoneal, perirenal and mediastinal fat depots are involved, while retroorbital fat seems to be spared. Muscle mass, evaluated by dual energy X-ray analysis (DEXA), is preserved or even increased compared to age-, sex- and body mass index (BMI)-matched subjects. Therefore, in spite of the generalised atrophy of fat...

As Sources Of Distress

Fatigue is one of the most limiting of the HIV syndromes in terms of quality of life and its incremental impact on dealing effectively with advancing HIV disease, comorbid depression, and hepatitis C coin-fection. HIV-related fatigue decreases functional status, which in turn can lead to symptoms of isolation, Fatigue also plays an important role in HCV infection, as fatigue is a common complaint among sufferers of HCV both prior to and during treatment with biological agents such as interferon-based therapies. Four hundred and eighty-four HIV-seropositive subjects participated in a self-report trial which confirmed that HCV-coinfected patients demonstrated significantly more elements of distress compared to the HIV-only group in social, psychological, and biological arenas. The patients were also more likely to be in unstable social situations and to experience depression, fatigue, and reduced quality of life (Braitstein et al., 2005).