Subtypes of Hepatitis B Antigen in Blood Donors and Post-transfusion Hepatitis: Clinical and Epidemiological Aspects

Subtyping of hepatitis B antigen (HBA) in blood donors revealed subtype ad in 56% while patients with icteric post-transfusion hepatitis from the same centre showed subtype ay in the majority of the cases (75%). Donors with subtype ad in serum were mostly asymptomatic long-term carriers of the antigen with normal liver function (83%), while 70% of donors with subtype ay in serum had signs of acute or chronic liver disease. Healthy long-term carriers of HBA seem to present little risk of transmitting hepatitis irrespective of subtype. It is, however, possible that these differences in blood donors with subtype ad and patients with post-transfusion hepatitis with subtype ay might reflect epidemiological circumstances rather than biological differences in the two viral strains.     

Chronic Hepatitis Associated with Drug Abuse: Significance of Hepatitis B Virus

One hundred and seventy-seven former heroin addicts, consisting of 85 who were newly admitted to a methadone maintenance program and 92 who had received methadone for a mean period of 30 months, were prospectively studied for up to 2 years in order to determine: (1) the effect of heroin withdrawal on the hepatic abnormalities, and (2) the incidence of HBsAg, anti-HBs, and anti-HCc as indices of the frequency of hepatitis B virus infection. Our study indicates that (1) hepatic abnormalities persist when heroin is discontinued and are not temporally related to drug and/or needle usage, and (2) that 71% of subjects had either HBsAg or anti-HBs; anti-HBc was tested for in 16 patients and was present in 100%, although 9 of the 16 were both HBsAg- and anti-HBs-negative. This study suggests that hepatitis B is largely responsible for the liver dysfunction. It is proposed that an abnormality in immune function, induced by heroin, is responsible for the high incidence of chronic hepatitis. Attention is drawn to the similarity between former drug addicts and hemophiliacs, since both develop chronic hepatitis in spite of anti-HBs in the serum.     

Infantile Hepatitis B in Immunized Children: Risk for Fulminant Hepatitis and Long-Term Outcomes

Background

Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B.

Methods

The clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median  = 4.4 years, range 0.6–18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed.

Results

Among the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age <7 months) and negative maternal hepatitis B e antigen (HBeAg) were associated with FH (p = 0.03 and p = 0.01, respectively). An infantile fulminant hepatitis B risk score using maternal/infant HBeAg positivity and onset age was proposed. Among the FH cases, the rate of mortality, HBsAg clearance, and chronic HBV infection were 47.6%, 38.1%, and 14.3%, respectively. Among the NFH cases, 35% developed chronic infection. Of the 9 chronically infected children received long-term follow-up, 8 had HBeAg seroconversion before 4 years of age. One case of FH developed hepatocellular carcinoma 14 years later.

Conclusions

Maternal HBsAg + /HBeAg- and early onset age were risk factors for FH in immunized infants. A significant portion of patients with FH or NFH evolve to chronic HBV infection, with HBeAg seroconversion in young childhood. Close surveillance for hepatocellular carcinoma is warranted in patients surviving infantile hepatitis B.     

Hepatitis vaccines: recent advances

Despite the availability of hepatitis A vaccines that might provide protection for decades, hepatitis B vaccines that provides protection for at least 15 years and the recent introduction of a combined hepatitis A and B vaccine, these infections continue to spread in both the developed and developing world. Hepatitis A vaccine coverage has been limited to high-risk groups: such a selective immunisation policy is unlikely to have a major impact. If adequate immunogenicity in infants is confirmed, dosing schedules can be improved and the costs of vaccination reduced, universal paediatric immunisation with combined hepatitis A and B products is likely to result in the eventual eradication of these infections. In the interim, novel hepatitis A vaccines are being investigated and additional studies on hepatitis A vaccine immunogenicity in infants are in progress. Worldwide use of hepatitis B vaccines for the newborn, young children and high-risk groups should control this infection and obviate the need for a vaccine against hepatitis D. Newer hepatitis B vaccines that may reduce the likelihood of non-responsiveness and have immunotherapeutic value are under study. A recombinant hepatitis E vaccine for use in endemic regions is currently in clinical trials. The development of an effective hepatitis C vaccine has been agonisingly slow and many impediments have been recognised. These include the lack of a susceptible small animal, a high degree of hepatitis C virus (HCV) genomic diversity and failure to produce high quantities of HCV in tissue culture. The development of a novel HCV replicon system may be a major breakthrough. Nonetheless, it may still be exceedingly difficult to produce a vaccine that uniformly provides sterilising immunity; the possibility of developing a hepatitis C vaccine that can prevent chronic infection is an exciting concept that requires further investigation. Advances in recombinant technology, the use of novel genetic (DNA-based) vaccines, expression of hepatitis antigens in plants and improved adjuvants also hold considerable promise.     

Hepatitis E: an overview

The hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA virus with icosahedral symmetry. Although it is related to the alpha-virus superfamily, the HEV is classified as a separate Hepatitis E-like viruses genus. Infection in humans occurs in sporadic and epidemic forms and can cause an acute, self-limited, icteric hepatitis. Recent studies indicate the existence of a reservoir in animals.     

Hepatitis C: a review

Hepatitis C virus is an RNA virus in the Flavivirus family that was identified in 1989. Since then, blood donor screening has reduced the incidence of acute infections; however, because this virus frequently leads to asymptomatic chronic infection, the prevalence of infection remains high. Chronic infection leads to increased risks of cirrhosis and hepatocellular carcinoma, as well as extrahepatic manifestations. Guidelines for widespread screening continue to evolve, and early diagnosis is likely to become more important with the development of more effective treatments. Current recommendations regarding screening are reviewed.     

Hepatitis C: molecular virology and antiviral targets

Chronic hepatitis C is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although current treatment options are limited, progress in understanding the molecular virology of hepatitis C has led to the identification of novel antiviral targets. Moreover, in vitro and in vivo model systems have been developed that allow systematic evaluation of new therapeutic strategies. This review details current concepts in molecular virology and emerging therapies for hepatitis C.     

Hepatitis viruses: characterization and diagnostic techniques.

Two human hypatitis viruses have been identified and characterized, but one or more additional agents exist. Hepatitis B virus (HBV) is a complex 42-nm predominantly double-stranded DNA virus with distinct surface and core antigens and an endogenous DNA polymerase. Hepatitis A virus (HAV) is a 27-nm RNA virus with enterovirus-like properties. Progressively more sensitive and specific immunologic assays have been applied to the study of viral hepatitis and are available for routine diagnostic purposes. As a result we recognize distinct serologic response patterns to infection, new antigenic markers, biochemical-biophysical characteristics of the viruses, and their epidemiologic features. Recombinant DNA technology has permitted the cloning of HBV genetic material and gene products in E. coli, but the virus has not been cultivated in vitro. In contrast, successful in vitro cultivation of HAV has finally been accomplished. Application of sensitive serologic tests for HAV and HBV has revealed that "non-A, non-B" agents account for a substantial proportion of transfusion-associated hepatitis as well as hepatitis occurring in the absence of percutaneous exposure. These agents have been transmitted to chimpanzees, and several putative virus antigen-antibody systems have been described; however, a specific association between these virus antigens and non-A, non-B hepatitis has not been established.     

Arthritis and Hepatitis

The evidence relating four clinically distinct rheumatologic syndromes to infection by the hepatitis B virus is reviewed. Acute hepatitis B is not infrequently heralded by a prodromal rash and rheumatoidlike polyarthritis. Chronic active hepatitis B more rarely is associated with transient arthritis or arthralgias. Polyarteritis nodosa may be a manifestation of hepatitis B infection in as many as 40 percent of cases, and recently the syndrome of “essential” mixed cryoglobulinemia has also been linked to infection with this virus. The finding of immune complexes of varying composition, sometimes with the viral antigen or its antibody (or both) contained in both the serum and synovial fluid suggests that these four syndromes are clinical manifestations of immune complex disease resulting from hepatitis B infection.     

Hepatitis virus vaccines: present status

During the past decade there has been extraordinary progress toward the development of vaccines for the prevention of type A and type B hepatitis. The successful propagation of hepatitis A virus in cell culture in 1979 was followed by the preparation of experimental live attenuated hepatitis A vaccines that have been shown to induce antibody in marmosets and chimpanzees and protect immunized marmosets against challenge with hepatitis A virus. The first human immunization trials will begin in mid-1982. An inactivated hepatitis B vaccine that was licensed in the United States in November 1981 has been shown to be safe, immunogenic, and effective. When this vaccine becomes available for use in July 1982, it will be recommended for persons who are considered to be at increased risk of contracting hepatitis B infection. Future generations of hepatitis B vaccines may be prepared from hepatitis B surface antigen derived from DNA recombinant technology or by in vitro synthesis of HBs Ag determinants by chemical means.     

Hepatitis C Virus: Assembly and Release of Virus Particles

Hepatitis C virus is a blood-borne virus that typically establishes a chronic infection in the liver, which often results in cirrhosis and hepatocellular carcinoma. Progress in understanding the complete virus life cycle has been greatly enhanced by the recent availability of a tissue culture system that produces infectious virus progeny. Thus, it is now possible to gain insight into the roles played by viral components in assembly and egress and the cellular pathways that contribute to virion formation. This minireview describes the key determining viral and host factors that are needed to produce infectious virus.