25 articles with citation and abstract regarding:

Hepatitis B
General Information
Treatment
Role of E-antigen

General Information - articles regarding general Hepatitis B information

What is Hepatitis B?

1. Lok ASF, McMahon B. Chronic Hepatitis B. HEPATOLOGY. 2001; 34: 1225-1241.

No abstract, however the first sentence is from the Preamble of the article:
"These guidelines have been written to assist physicians and other health care providers in the recognition, diagnosis, and management of patients chronically infected with the hepatitis B virus (HBV)."

What are the details (the biology) of Hepatitis B?

2. Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004 Mar 11;350(11):1118-29

In the past 10 years, remarkable strides have been made in the understanding of the natural history and pathogenesis of hepatitis B virus (HBV) infection. In this article we will review these advances, with particular reference to the implications for antiviral therapy.

3. Fattovich G. Natural history of hepatitis B. J Hepatol. 2003;39 Suppl 1:S50-8.

No abstract, however the first sentence is from the Summary of the article:
Hepatits B virus (HBV) infection can cause acute, fulminant or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC).

4. Fattovich G.  Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003 Feb;23(1):47-58.

The natural history of hepatitis B virus (HBV) infection is complex and variable and is greatly influenced by the age at infection, the level of HBV replication, and host immune status. Chronic HBV infection generally consists of an early replicative phase with active liver disease (hepatitis B e antigen [HBeAg]-positive chronic hepatitis) and a late low or nonreplicative phase with HBeAg seroconversion and remission of liver disease (inactive carrier state). After HBeAg seroconversion, some patients may have active hepatitis due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Morbidity and mortality are linked to development of cirrhosis and hepatocellular carcinoma. Survival is reasonably good (about 85% probability at 5 years) in compensated cirrhosis but very poor in decompensated cirrhosis. Both cirrhotic and noncirrhotic patients with sustained reduction of HBV replication and normalization of aminotransferase after interferon alfa therapy have a reduced risk for liver-related complications.

5. Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev. 2000 Mar;64(1):51-68.

Hepadnaviruses (hepatitis B viruses) cause transient and chronic infections of the liver. Transient infections run a course of several months, and chronic infections are often lifelong. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. The replication strategy of these viruses has been described in great detail, but virus-host interactions leading to acute and chronic disease are still poorly understood. Studies on how the virus evades the immune response to cause prolonged transient infections with high-titer viremia and lifelong infections with an ongoing inflammation of the liver are still at an early stage, and the role of the virus in liver cancer is still elusive. The state of knowledge in this very active field is therefore reviewed with an emphasis on past accomplishments as well as goals for the future.

6. Chang MH. Natural history of hepatitis B virus infection in children. J Gastroenterol Hepatol. 2000 May;15 Suppl:E16-9.

Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant or chronic hepatitis, liver cirrhosis, and liver cancer. Approximately 90% of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2-7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by an elevation of aminotransferases. In a long-term follow-up study, the annual HBeAg seroconversion rate was 4-5% in children older than 3 years of age and less than 2% in children under 3 years. The annual seroconversion rate of HBsAg was very low (0.56%). Age at infection, maternal HBsAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children.

Treatment

7. Liaw YF. Therapy of chronic hepatitis B: current challenges and opportunities. J Viral Hepat. 2002 Nov;9(6):393-9.

Better understanding of hepatitis B virus (HBV) replication, natural history and the immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action are the basis for better therapeutic strategies against chronic hepatitis B. Among currently available drugs, interferon-alpha and thymosin-alpha1 have only modest efficacy (approximately 40% vs 9-20% in controls). In the past decade, lamivudine has dominated in the treatment of chronic HBV infection because it is easy to use, safe, and is effective in terms of hepatitis B e antigen and/or HBV-DNA loss, ALT normalization, and improvement in histology. The response rate increases with increasing pretherapy alanine aminotransferase (ALT) levels, suggesting that patients with stronger endogenous immune response against HBV have a better response to direct antiviral agents. Lamivudine is also beneficial in decompensated cirrhotics with HBV replication. Hepatitic flares may occur after stopping lamivudine therapy in nonresponders and also in responders. Therefore, prolonged therapy is usually required. However, tyrosine-methionine-aspartate-aspartate (YMDD) mutations conferring resistance to lamivudine start to emerge after 6-9 months of therapy, and hepatitis flare, even decompensation, may develop after viral breakthrough. Thus the benefits of long-term lamivudine therapy must be balanced against the concern about YMDD mutations and the durability of treatment response. Adefovir dipivoxil, entecavir, emtricitabine, clevudine and other nucleoside/ nucleotide analogues have shown encouraging results and some agents appear effective in patients with YMDD mutants. Further development of new drugs and new strategies may help to improve treatment in the new century.

8. van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat. 2003 Jul;10(4):294-7.

Vertical transmission of hepatitis B virus (HBV) can occur occasionally despite vaccination of the child. This vaccination breakthrough has been associated with high maternal viraemia. We treated eight highly viraemic (HBV-DNA >/= 1.2 x 10(9) geq/mL) mothers with 150 mg of lamivudine daily during the last month of pregnancy. HBV-DNA, hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc of their offspring were measured at birth and at 3, 6 and 12 months, respectively. Twenty-four children, born to untreated HBsAg-positive mothers with HBV-DNA levels >/=1.2 x 10(9) geq/mL served as historical controls. All children received passive-active immunization at birth and were followed-up for 12 months. In the lamivudine group one of the eight children (12.5%) was still HBsAg and HBV-DNA positive at the age of 12 months. All other children seroconverted to anti-HBs and maintained seroprotection. In three children, HBV-DNA was temporarily detected by polymerase chain reaction. In the untreated historical control group, perinatal transmission occurred in seven of 25 children (28%). In highly viraemic HBsAg-positive mothers, reduction of viraemia by lamivudine therapy in the last month of pregnancy may be an effective and safe measure to reduce the risk of child vaccination breakthrough. This approach should be evaluated in a large controlled trial.

9. Dando T, Plosker G. Adefovir dipivoxil: a review of its use in chronic hepatitis B. Drugs. 2003;63(20):2215-34.

Adefovir dipivoxil (Hepsera) is an oral prodrug of the nucleotide analogue adefovir. It is indicated for the treatment of chronic hepatitis B in adults. Adefovir dipivoxil 10 mg/day significantly improved histological, biochemical and virological outcomes in hepatitis B e antigen (HBeAg)-positive and -negative patients, and serological outcomes in HBeAg-positive patients. In two trials, the proportion of adefovir dipivoxil recipients showing histological improvement in the liver was approximately twice that for placebo recipients. In two trials in patients chronically infected with lamivudine-resistant hepatitis B virus (HBV), switching to or adding adefovir dipivoxil was significantly more effective at reducing serum HBV DNA levels than continuing lamivudine monotherapy. In treatment-naive patients, 1 year's treatment with adefovir dipivoxil plus lamivudine had similar efficacy to lamivudine plus placebo; however, lamivudine-resistant HBV emerged in significantly more patients receiving lamivudine plus placebo. Adefovir dipivoxil has also shown efficacy in noncomparative trials in patients with decompensated liver disease, patients co-infected with HIV and patients pre- or post-liver transplantation. Within 96 weeks of treatment with adefovir dipivoxil, a resistance-conferring mutation emerged in viral isolates from 1.6% of patients. In vitro, these isolates remained sensitive to lamivudine, while lamivudine-resistant HBV isolates remained sensitive to adefovir dipivoxil. Adefovir dipivoxil 10 mg/day is generally well tolerated. In a pooled analysis of 48-week data from two trials, there was no marked difference in adverse events or laboratory abnormalities between adefovir dipivoxil and placebo recipients. Within 96 weeks of treatment with adefovir dipivoxil, >1% of patients with adequate renal function developed an increase in serum creatinine levels of >/=0.5 mg/dL above baseline. Within 48 weeks of treatment, increases in serum creatinine levels of >/=0.5 mg/dL above baseline were observed in 13% of pre- and post-liver transplantation patients who generally had renal insufficiency or risk factors for renal dysfunction at baseline. Most patients continued treatment with dosage adjustments. CONCLUSION: Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV. Few resistant HBV mutants have emerged to date. Data from ongoing long-term studies are awaited with interest. Existing treatment options for patients with chronic hepatitis B are limited in both number and effectiveness; the proven efficacy, good tolerability profile and apparently low potential for resistance of adefovir dipivoxil make it a promising new option in the management of this disease.

10. Heathcote J. Treatment of HBe antigen-positive chronic hepatitis B. Semin Liver Dis. 2003 Feb;23(1):69-80.

Spontaneous loss of hepatitis B e antigen (HBeAg) followed by seroconversion to anti-HBe usually coincides with normalization of serum alanine aminotransferase (ALT) levels, reduction in HBV DNA in serum (< 1 x 10(6) copies/mL), and a marked reduction in hepatic inflammation. Licensed antiviral therapies are the interferon (IFN) alphas and the nucleoside analogue lamivudine. Both drugs enhance the rate at which HBeAg seroconversion takes place and thus reduce progression of disease. These therapeutic agents are ineffective if given when there is no ongoing hepatitis (i.e., normal ALT), and their efficacy is greatest in individuals with the most active disease. The effectiveness of these two classes of drugs is similar, and it is possible that the two therapies combined are more effective than monotherapy with either drug. A high side-effect profile and the high risk of further morbidity when given to patients with decompensated disease limit the use of IFN-alpha. When prescribing lamivudine, drug resistance that increases with duration of therapy and the potential risk of a severe flare of hepatitis with sudden cessation of therapy, probably greatest in patients with cirrhosis, are realistic concerns. Both patient and physician need to recognize the need for close monitoring both during and after cessation of any antiviral therapy for hepatitis B.

General Information

11. Siegl G. [Hepatitis A virus infection. A review]. Schweiz Rundsch Med Prax. 2003 Oct 1;92(40):1659-73.

[Article in German]

The virus responsible for hepatitis A--hepatitis A virus (HAV)--is a small, spherical, and exceptionally resistant RNA-virus. It is transmitted preferentially by the faecal-oral route and apparently replicates exclusively in the liver. The damage of the liver ensuing from HAV infection most likely does not stem directly from virus replication but is the result of an interaction of cell mediated virus.-specific immunity with infected hepatocytes. Infection is usually self limiting, yet, in individual cases may also take a protracted and even relapsing course. True chronic infections, however, are not observed. HAV has a world-wide distribution. In countries where inadequate sanitary conditions prevail, the virus persists in the environment and almost 100% of the population acquires infection in childhood. At that age, infection causes no or only minimal clinical symptoms. Infected individuals nevertheless develop protective, long lasting immunity, probably persisting for entire life. In developed, industrialized countries HAV has ceased to circulate in the environment and the general population. Here, infections predominantly occur in adults travelling to endemic areas or exposed at home to thus infected individuals or members of high risk groups (e.g. children in day care centres, i.v. drug users). With increasing age infections become more and more clinically manifest and at and beyond of adolescence more than 80% of patients develop icteric, in some cases even fulminant and fatal hepatitis. Acute hepatitis A infection can be diagnosed by demonstrating the presence of anti-HAV-IgM antibodies. Immunity following either infection or successful vaccination is assessed by measuring anti-HAV-IgG. Preventive measures rely on strict personal and alimentary hygiene as well as on vaccination with inactivated (killed) hepatitis A vaccines. These vaccines are safe, highly immunogenetic and induce long lasting (> 20 years) protection against hepatitis A. Specific antiviral therapy is not yet available.

12. Jenson HB. The changing picture of hepatitis A in the United States. Curr Opin Pediatr. 2004 Feb;16(1):89-93.
    

PURPOSE OF REVIEW: Hepatitis A causes approximately half of the cases of viral hepatitis in the United States. Since 1999, routine hepatitis A immunization of children in areas of the United States with high rates of hepatitis A has been recommended. RECENT FINDINGS: There has been an increasing appreciation of the role of young children with asymptomatic or inapparent infection as the community reservoir of hepatitis A virus. Epidemiologic studies have demonstrated striking geographic variations in the incidence of hepatitis A in the United States. On the basis of this understanding, recommendations for control of hepatitis A were updated in 1999 to include routine vaccination of children living in states, counties, and communities with high rates of hepatitis A. Routine hepatitis A vaccination of children in areas with high rates of hepatitis A is a cost-effective strategy to reduce the incidence of hepatitis A. SUMMARY: Improved understanding of the epidemiology and transmission of hepatitis A combined with the availability of effective hepatitis A vaccines have dramatically reduced the burden of hepatitis A in the United States.

13. Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis. 2004 Mar 1;38(5):705-15. Epub 2004 Feb 11

Hepatitis A is caused by hepatitis A virus (HAV). Transmission occurs by the fecal-oral route, either by direct contact with an HAV-infected person or by ingestion of HAV-contaminated food or water. Foodborne or waterborne hepatitis A outbreaks are relatively uncommon in the United States. However, food handlers with hepatitis A are frequently identified, and evaluation of the need for immunoprophylaxis and implementation of control measures are a considerable burden on public health resources. In addition, HAV-contaminated food may be the source of hepatitis A for an unknown proportion of persons whose source of infection is not identified.

14. Kiyasu PK, Caldwell SH. Diagnosis and treatment of the major hepatotropic viruses. Am J Med Sci. 1993 Oct;306(4):248-61.

The hepatotropic viruses currently include hepatitis A, B, C, D, and E, and are associated with a spectrum of acute and chronic liver disease syndromes. The epidemiology and natural history of each are discussed, with emphasis on uncommon or newly recognized clinical presentations. The serodiagnosis of hepatitis A, B, and D is well established; the serodiagnosis of hepatitis C and E continues to evolve as serologic and virologic assays become refined. Hepatitis A and E only cause acute liver injury; current medical approaches therefore focus on vaccination strategies. Hepatitis B, C, and D can cause both acute and chronic liver injury. Sequelae of chronic liver disease, including portal hypertension and hepatocellular carcinoma, are not uncommon. Medical therapy of resulting chronic liver disease currently consists of interferon, though other anti-viral strategies are being explored. Advanced chronic liver disease due to hepatitis B, C, or D can be treated by orthotopic liver transplantation, but viral recurrence is near uniform and can be problematic. Further study of the hepatotropic viruses at the molecular biologic, epidemiologic, and clinical levels will continue to provide greater insight into the diagnosis and management of their associated clinical syndromes.

General Information

15. J. C. L. Booth. Chronic hepatitis C: the virus, its discovery and the natural history of the disease. Journal of Viral Hepatitis Volume 5 Issue 4 Page 213 - July 1998

The identification of hepatitis A and hepatitis B led to the recognition that a third virus was capable of causing blood-borne hepatitis. The pathogen responsible for this nonA, nonB hepatitis was identified in the late 1980s and subsequently named hepatitis C. Since the discovery of hepatitis C there has been a pandemic of research publications describing the natural history of the infection and it is now known that this virus can cause serious liver damage in a proportion of infected patients. It is now clear that the effects of infection with hepatitis C and alcohol misuse are additive and that there is an increased risk of hepatic complications in infected patients who abuse alcohol.

16. Stephenne X, Sokal EM. Hepatitis C in children and adolescents: mode of acquisition, natural history and treatment. Acta Gastroenterol Belg. 2002 Apr-Jun;65(2):95-8.

Hepatitis C is nowadays mainly acquired in childhood through vertical transmission, while transfusion or surgery related contamination is no more significant. The risk of maternal transmission is related to presence and amount of maternal HCV RNA at the time of delivery. Infection rate is higher in children form HIV positive mothers, and higher if they are themselves co-infected with HIV. Breast milk feeding is not a risk factor, and there is so far no argument to propose cesarean delivery to HCV positive mothers. Treatment with interferon alone is poorly efficient, although pediatric studies remain scarce. Combination treatment using Ribavirin plus interferon, or Ribavirin + pegylated interferon yield a higher success in eradicating viral infection in adults. These treatments can be considered for children in selected cases.

17. Szabo E, Lotz G, Paska C, Kiss A, Schaff Z. Viral hepatitis: new data on hepatitis C infection. Pathol Oncol Res. 2003;9(4):215-21. Epub 2003 Dec 22.

Viral hepatitis (VH) is almost as old as human beings, at least as old as known human history. However, the natural history and the epidemiology of the disease has undergone changes during the centuries and even recently we have been facing several new aspects. The estimated global prevalence is around 3-5%, which means that approximately 400 million patients are infected with hepatitis B virus and that there are 170 million infections with hepatitis C virus. The mortality figures are projected to show a 2- to 3-fold increase over the next two decades as hepatitis C virus-infected patients develop cirrhosis, which makes this the leading indication for liver transplantation. These data point to the importance of VH being a significant public health problem worldwide. The list of hepatotropic viruses is well known, including hepatitis A (HAV), B (HBV), C (HCV), D (HDV), E (HEV), G (HGV) and F (HFV). HGV and HFV are excluded from the present review, mainly because they are questionable in relation to the causation of liver disease. Our knowledge of HAV, HBV, HDV and HEV has accumulated over the last decade, so the present discussion is focused on HCV, which is currently generating considerable concern and controversy, and is the leading cause of chronic liver disease worldwide. The main questions to be discussed, are: the characterization of the agents' viral genotypes/subtypes, the viral-cell interaction, the pathogenesis of VH, the extrahepatic manifestations of viral infection and hepatocarcinogenesis.

Treatment

18. Pham TN, MacParland SA, Mulrooney PM, Cooksley H, Naoumov NV, Michalak TI. Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C. J Virol. 2004 Jun;78(11):5867-74.

It is presumed that resolution of hepatitis C, as evidenced by normalization of liver function tests and disappearance of hepatitis C virus (HCV) RNA from serum, as determined by conventional laboratory assays, reflects virus eradication. In this study, we examined the expression of the HCV genome in the sera, peripheral blood mononuclear cells (PBMC), and, on some occasions, monocyte-derived dendritic cells (DC) long after resolution of hepatitis C by using a highly sensitive reverse transcription (RT)-PCR-nucleic acid hybridization (RT-PCR-NAH) assay. The samples obtained from 16 randomly selected patients (5 with spontaneous and 11 with treatment-induced resolution), monitored for up to 5 years, were studied by qualitative and semiquantitative RT-PCR-NAH and by real-time RT-PCR to detect the HCV RNA positive strand. The replicative HCV RNA negative strand was examined in PBMC after culture with a T-cell proliferation stimulating mitogen. The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated. Also, DC from six of seven patients were reactive for the HCV genome. Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery. Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively. These results imply that HCV RNA can persist at very low levels in the serum and peripheral lymphoid cells and that an intermediate replicative form of the HCV genome can persist in PBMC for many years after apparently complete spontaneous or antiviral therapy-induced resolution of chronic hepatitis C.

19. Ahmed A, Keeffe EB. Update on chronic hepatitis C. Compr Ther. 2003 Winter;29(4):224-32.

Strategies for the diagnosis and treatment of chronic hepatitis C continue to evolve. Liver biopsy is now used selectively rather than routinely, and the combination peginterferon plus ribavirin is the treatment of choice for the majority of patients.

20. Kryczka W, Zarebska-Michaluk D. Treatment of acute hepatitis C. Med Sci Monit. 2003 Aug;9 Suppl 3:22-4.

BACKGROUND: We presented the results of treatment in patients with AHC and compared these findings with natural outcome of AHC in untreated patients. MATERIAL/METHODS: Ten treated AHC patients (5F/5M, mean age: 35.5 yrs; all HCV-RNA-positive including 9 anti-HCV-positive). Antiviral treatment was started within 3 to 18 (median 9) weeks after the onset of acute hepatitis including eight patients with monotherapy of IFN and two patients with combined (IFN + ribavirin) therapy. CONTROL GROUP: Fifty consecutive untreated AHC patients (26F/24M, mean age: 40.8 yrs; all HCV-RNA-positive, including 29 anti-HCV-positive) without contraindications to treatment with IFN. RESULTS: Only one treated patient presented no response and the other 9 patients presented rapid normalization of serum ALT levels in 4th-6th week of the therapy. In two patients, ALT increased in the course of therapy and after adding ribavirin the treatment was continued up to 48 weeks in total. At the end of treatment point, nine patients showed biochemical and virological response, but one relapsed both in biochemical and virological respect and virological relapse was observed in another one. Finally, sustained response was observed in 7 of 10 (70%) of treated compared with 22 of 50 (44%) untreated patients (p = n.s.). The beneficial effect of antiviral treatment was observed among patients with early anti-HCV seroconversion: 7 of 9 treated patients recovered persistently compared with 8 of 29 untreated (p = 0.021). CONCLUSIONS: The antiviral therapy in AHC seems to be effective and should be widely used, especially for individuals with early anti-HCV seroconversion. Ribavirin seems to be helpful for patients, who have not responded to interferon monotherapy.

21. Kakimi K. Immune-based novel therapies for chronic hepatitis C virus infection. Hum Cell. 2003 Dec;16(4):191-7.

Hepatitis C virus (HCV) infection is a great public health problem, with an estimated 200 million chronically infected patients worldwide. No vaccines are currently available for HCV, and only a subset of HCV patients responds to interferon-alpha (IFN-alpha) and Ribavirin treatment. Substantial evidence has emerged recently to support the role of the host immune response in the outcome and pathogenesis of HCV infection. Our aims of this article are to present the immune-based novel therapeutic options for HCV infection and the evidence supporting their use in patients with chronic hepatitis C. There is a growing consensus that acute control of HCV infection is associated with a vigorous intrahepatic antiviral CD4+ and CD8+ T cell response. IFN-gamma was detectable in the livers of the chimpanzees that cleared or controlled the virus, raising the possibility that IFN-gamma might perform antiviral effector functions during HCV infection. Based on these observations, therapeutic induction of intrahepatic IFN-gamma by adoptive immunotherapy might be able to control chronic HCV infection. Immune-based novel therapies appear to hold great promise in treating chronic HCV infection.

Hepatitis E

22. Schlauder GG, Mushahwar IK. Genetic heterogeneity of hepatitis E virus. J Med Virol. 2001 Oct;65(2):282-92.

Hepatitis E virus (HEV) infection has been considered a disease associated with developing regions and attributed to oral-fecal transmission due to inadequate sanitation. Several recent findings, however, have led to a new understanding of this virus. A number of novel isolates have been identified in patients with acute hepatitis from regions not considered endemic for HEV, and these individuals reported no recent travel to HEV endemic areas. In addition, a number of HEV-like sequences have also been isolated from swine worldwide, suggesting the potential of an animal reservoir. Although full-length sequence is available for some strains, the majority of HEV isolates have only been sequenced partially. Sequence comparisons and phylogenetic analyses were performed to determine the genotypic distribution of HEV isolates, based on the partial sequence data available. It has been suggested that HEV isolates segregate into four major genotypes based on full-length comparisons. These analyses, however, indicate that HEV may be distributed into at least nine different groups.

23. Mast EE, Purdy MA, Krawczynski K. Hepatitis E. Baillieres Clin Gastroenterol. 1996 Jul;10(2):227-42.

Hepatitis E has a world-wide distribution and causes substantial morbidity and mortality in some developing countries, particularly among pregnant women. Hepatitis E virus (HEV) has recently been cloned and sequenced, and new diagnostic tests have been developed. These tests have been used to begin to characterize the natural history and epidemiological features of HEV infection. Experimental vaccines have also been developed that offer the potential to prevent hepatitis E. However, much remains to be learned about HEV, including the mechanisms of transmission, the reservoir(s) of the virus, and the natural history of protective immunity in order to develop effective strategies to prevent this disease.

Hepatits G

24. Tucker TJ, Smuts HE. Review of the epidemiology, molecular characterization and tropism of the hepatitis G virus/GBV-C. Clin Lab. 2001;47(5-6):239-48.

The hepatitis G virus and GBV-C are recently discovered variants of the same virus belonging to the family Flaviviridae (HGV/GBV-C). Although initially thought to be a hepatitis virus, it has been shown to have no association with liver disease. This paper reviews the data relating to the discovery, global prevalence, natural history, disease association, molecular features, replication and tissue tropism of HGV/GBV-C.

25. Karayiannis P, Pickering J, Zampino R, Thomas HC. Natural history and molecular biology of hepatitis G virus/GB virus C. Clin Diagn Virol. 1998 Jul 15;10(2-3):103-11.

BACKGROUND: The hepatitis G virus (HGV) or GB virus C (GBV-C) is a new member of the Flaviviridae family. The virus is transmitted by transfusion of blood, infusion of some blood products, and by parenteral exposure to blood during intravenous drug use (IVDU) and haemodialysis. Transmission from mother to infant and by sexual contact has also been documented. Although the virus has been found in patients with acute and chronic hepatitis, evidence of disease association has not been forthcoming. The majority of patients carry the virus in the absence of liver enzyme abnormalities. OBJECTIVES: To review what is currently known about HGV/GBV-C in order to evaluate its similarity with other members of the Flaviviridae and the association of the virus with disease. RESULTS: The genomic organisation of the virus is typical for Flaviviridae, with long 5' and 3' untranslated regions (UTR). However, a clearly identifiable nucleocapsid encoding region is lacking. Polyprotein synthesis is mediated through an internal ribosome entry site (IRES) contained within the 5' UTR. Phylogenetic tree analysis of sequences derived from this region has demonstrated the existence of at least three genotypes. Apart from serum, HGV-RNA has been detected in lymphocytes also, but the quasispecies present in the two compartments appear to be different. The envelope glycoprotein E2 lacks a hypervariable region and is potentially the target of a neutralising antibody response. CONCLUSION: Molecular analysis of HGV reveals close similarity of the virus with HCV. However, an association of the virus with liver disease remains unresolved and no association of the virus with hepatocellular carcinoma has been reported.