Hepatitis Virus Type Research Articles

Hepatitis A and HIV: A Clinical Review of Disease and Strategies for Prevention

Hepatitis A, also known as infectious hepatitis, remains one of the more commonly transmitted types of viral hepatitis in the United States. Given the high prevalence of this illness, clinicians need to be aware not only about the clinical manifestations of this disease, but also about the special considerations that must be taken into account for persons coinfected with HIV. Antiretroviral management during acute hepatitis infection may be complicated by elevations of serum liver enzyme tests as well as by severe manifestations of associated symptoms such as nausea and vomiting. This article provides a brief overview of the clinical course of HIV infection and includes recommendations for antiretroviral medication management during acute illness. Additionally, strategies for prevention of disease are presented, with a focus on the efficacy and use of hepatitis A vaccines in persons with HIV.

Clinical and viral marker pattern of acute sporadic hepatitis in children in Madras, South India.

One hundred and twenty-seven children who presented with features of acute hepatitis during the period February 1995 to January 1996 were studied. Specific aetiologic agents were identified in 89 per cent. Of these, 67.7 per cent were due to a single virus, whereas 21.3 per cent were due to two or more hepatitis viruses. Hepatitis A virus (HAV) was the sole infecting agent in 38.6 per cent of cases, hepatitis B virus (HBV) in 13.4 per cent of cases, and hepatitis E virus (HEV) in 15.7 per cent of cases. Mixed infections were due to HAV and HBV co-infection (7.1 per cent), HAV and HEV (13.4 per cent), and the combination of HAV, HBV, and HEV (0.8 per cent). In 11 per cent, none of the markers (HAV to HEV) were identified. Acute sporadic hepatitis in children can occur due to a single hepatitis virus type or, at times, due to co-infection with a combination of two enterally transmitted viruses or enteral and parenterally transmitted viruses. Improving personal hygiene and active immunization are essential in the prevention of these viral illnesses. This study was done in a referral centre and hence we report a higher morbidity (13.4 per cent) and mortality (12.6 per cent) rate in all groups of infection. Hence, apart from the viruses, factors such as the age of the child, nutritional status, and treatment taken prior to hospitalization should be taken into consideration to predict the prognosis in a given child.

Different intrahepatic recurrence rate after resection of hepatocellular carcinoma associated with chronic hepatitis B and C

Hepatocellular carcinoma (HCC) occurs more prevalently in livers, not only with cirrhosis but chronic hepatitis due to hepatitis C virus (HCV), than in hepatitis B virus (HBV) related counterparts. This study aimed to investigate intrahepatic recurrence (IHR) and underlying mechanisms after resection of HCC associated with chronic hepatitis B and C from the viewpoint of hepatocarcinogenesis. A total of 44 patients with HCC and chronic hepatitis due to HBV in 15 patients and HCV in 29 patients were carefully followed up after curative hepatic resection. Clinical backgrounds, preoperative laboratory data, histopathologies of HCC and liver were compared between the two groups. Prognostic factors were analyzed by univariate and multivariate analyses. There were no differences in clinical backgrounds except for higher age in C hepatitis ( P=0.0048). Preoperative laboratory data were better in B hepatitis; AST ( P=0.0021, t-test), ALT ( P=0.0039), albumin ( P=0.0230), ICG test ( P=0.0043), platelet count ( P=0.0080), and plasma fibrinogen ( P=0.0224). No significant differences were found in tumor size or stage and other tumoral factors. Although the extent of hepatic fibrosis was similar, necroinflammatory activity was higher in C hepatitis ( P=0.0081). IHR rate was higher in C (65.5%) than in B hepatitis ( P=0.0145), but there was no difference in the recurrence pattern and time. The 5-year disease-free survival rate was 10.9% in C versus 84.6% in B hepatitis ( P=0.0018, log-rank test; P=0.0068, Wilcoxon test). Multivariate analysis revealed that the type of hepatitis virus and tumor size were independent factors for IHR. IHR occurs more frequently in chronic hepatitis C. Higher age and higher hepatitis activity may partly be responsible for this but further studies are necessary to elucidate the differences in carcinogenic potential and mechanism between chronic hepatitis B and C.

Resistance to murine hepatitis virus strain 3 is dependent on production of nitric oxide.

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.

Hepatitis in pregnancy

Currently, six distinct types of hepatitis virus have been identified: A, B, C, D, E, and G. Hepatitis A virus infection does not cause a chronic carrier state, and perinatal transmission is extremely uncommon. Hepatitis B can be transmitted perinatally, but immunization of the newborn with hepatitis B immune globulin and hepatitis B vaccine markedly reduces the risk of neonatal infection. Hepatitis D virus is dependent on coinfection with the hepatitis B virus for replication. Immunoprophylaxis against hepatitis B also is effective against hepatitis D. Hepatitis C virus is primarily transmitted by the parenteral route and is particularly likely to cause chronic liver disease. Perinatal transmission of hepatitis C principally occurs in women who have high titers of HCV-RNA or who are coinfected with human immunodeficiency virus. At this time, no immunoprophylaxis for hepatitis C is available. Hepatitis G, a recently described organism, is related to hepatitis C. Its clinical significance remains undetermined. Hepatitis E is transmitted in a manner similar to hepatitis A. Perinatal transmission is unusual, but maternal disease is often severe.

Immunodepression induced by Trypanosoma cruzi and mouse hepatitis virus type 3 is associated with thymus apoptosis.

Trypanosoma cruzi-infected mice show disturbance in the peripheral immune system such as polyclonal lymphocyte activation, autoantibody production, and immunosuppression of T lymphocytes. Previous observations in our laboratory showed that some stocks of T. cruzi can be contaminated with mouse hepatitis virus type 3 (MHV-3). Literature has shown that MHV-3 infection induces immunologic disorders characterized by thymic involution with marked cell depletion. However, the effects of interactions between MHV-3 and the parasite on the immune system are not well understood. In the present study specific-pathogen-free CBA mice were inoculated with MHV-3, alone or associated with different stocks of T. cruzi. Concurrent murine virus infection resulted in increased pathogenicity of T. cruzi infection shown by profound thymic atrophy; loss of cortical thymocytes; depletion of Thy1.2+, CD4+, and CD8+ cells; enhancement of in situ labeling of nuclear DNA fragmentation; and eventually, death of the animals. Such lines of evidence show that the mechanism underlying this thymic atrophy is associated with apoptosis. These results also suggest that MHV-3 can account for the increased immunosuppression observed during experimental infection with the parasite.

Intrahepatic alpha beta-TcRintermediate LFA-1high T cells are stimulated during mouse hepatitis viral infection.

Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of thymic and extrathymic T cell subpopulation disorders induced during the viral hepatitis. To understand local hepatic immune responses, the phenotypes of resident hepatic lymphocytes were determined and compared that of splenic and thymic T cell subpopulations during the acute viral hepatitis induced by MHV3 in susceptible C57BL/6 mice. Single positive (SP) CD4+ or CD8+ cells strongly increased in the liver. A specific cell population, the double positive (CD4+ C8+) cells, normally present in liver and thymic cell preparations, decreased in C57BL/6 mice following the viral infection. alpha beta-TcRintermediate T cells shifted toward alpha beta-TcRhigh T cells in the liver and thymus of infected mice, but not in their spleen. The specific alpha beta-TcRint or high lymphocytes occurring in the liver of MHV3-infected mice expressed higher levels of leukocyte function antigen-1 (LFA-1) and Pgp-1 (CD44) activation markers, suggesting that they were either activated or antigen-experienced during the viral infection. No significant changes in T cell subpopulations were detected in the spleen. These observations suggest that MHV3 infection could induce an early in situ stimulation of resident hepatic T cells, despite a peripheral immunodeficiency in the thymus and spleen.

Clonal deletion of some V beta+ T cells in peripheral lymphocytes from C57BL/6 mice infected with MHV3.

Mouse hepatitis virus type 3 infection is generally accompanied by a severe immune dysfunction involving thymic or splenic T cell subpopulations. We postulate that the peripheral lymphoid cell depletions were caused by a selective deletion of some V beta subsets of mature T cells, as observed with superantigens. We have examined the expression of V beta 6, V beta 8 and V beta 14 in T cell subpopulations from the spleen and lymph nodes of pathogenic L2-MHV3-infected C57BL/6 mice. Cytofluorometric study showed decreases in splenic V beta 8+, V beta 6+, and V beta 14+ T cell subpopulations at 72 hrs post-infection. Single positive CD4+ T cells were diminushed but not the CD8+ cells. In contrast, the various V beta splenic cell populations were not modified in mice infected with a non- pathogenic YAC-MHV3 variant. However, the V beta 8/CD4 ratio increased in splenic cells but decreased in lymphocytes from lymph nodes. The V beta 14/CD4 ratio decreased only in splenic cells while V beta 6/CD4 ratios were not modified. These results suggest that alterations in V beta cell populations may play a role in the L2-MHV3-induced immunodeficiency.

Viral hepatitis: update

The authors present an update related to different types of viral hepatitis in infancy. The clinic-laboratorial and special outcome aspects are presented. The most important articles about viral hepatitis were selected through Medline. The epidemiologic and clinical characteristics related to the subject are reported with emphasis on Brazilian data. This review analyzes the diseases caused by agents that have in common the viral origin and the hepatotropism, but the hepatitis are different particularly in those aspects related to outcome and prognosis. The B virus, for example, may be related to healthy asymptomatic carrier to acute hepatitis, chronic disease, cirrhosis and hepatocellular carcinoma. To date the known viruses are six: A, B, C, D, E and G. Viral hepatitis is a disease caused by one of the 6 different hepatotropic viruses which originate a wide range of clinical presentations. The viral distribution in Brazil is irregular; in some regions the B virus is prevalent, in others it is rare. The viral infections are the most important and the most frequent causes of liver disease in Brazilian children. The present review is to update viral hepatitis in infancy.

Controversies in diagnosis and treatment of hepatitis C

PREVIEWHepatitis C virus has recently been identified as an important cause of morbidity and mortality worldwide. Acute hepatitis C infection is clinically indistinguishable from other types of viral hepatitis but is much more likely to become chronic. Chronic hepatitis C is a significant cause of cirrhosis and hepatocellular carcinoma. While modes of transmission, diagnosis, and treatment are currently controversial, Dr Brady discusses some approaches for dealing with this emerging problem.

Epidemiological study of viral hepatitis types A, B, C, D and E among Inuits in West Greenland

A descriptive study was performed to evaluate the relative frequencies and molecular epidemiological features of viral hepatitis types A to E among the Inuit population in West Greenland. Serum samples were collected from 503 Inuits (186 males and 317 females; mean age 35 years; range 7-79 years) and were tested for markers of viral hepatitis infection. The hepatitis A prevalence averaged 54%, with a significant rise from 9% to 50% between the second and third decade of life. As for hepatitis B, 42% of the total study population showed serological evidence of current or past hepatitis B virus (HBV) infection and 7% were hepatitis B surface antigen (HBsAg) carriers. Among the carriers, 6% were also positive for hepatitis B e antigen (HBeAg), and HBV DNA could be detected in 49% of carriers by polymerase chain reaction. Typing of the HBV isolates revealed genomic group D in 83% (serotype ayw2) and group A in 17% (serotype adw 2). Less than 1% of the study population had antibodies to the hepatitis C virus. None were positive for HCV RNA. Serological evidence of hepatitis D infection was found in 7% of those with hepatitis B helper virus infection markers and in 40% of the HBsAg carriers. As for hepatitis E, 3% of the Inuits showed reactivity in an enzyme immunoassay that detected hepatitis E virus antibody. HEV RNA could not be detected.

Hepatitis Viruses and the Neonate

Great progress has been made in the last 10 years in the understanding of the various types of viral hepatitis, and new viruses, concepts, therapies, preventive measures, and control strategies have been recognized. Even more agents, vaccines, and drugs will be discovered or developed in the future, and pediatricians increasingly will be expected to provide guidance to patients and to the community on the importance and use of these new tools.

HEPATITIS IN THE OBSTETRIC PATIENT

The six agents identified thus far that cause viral hepatitis are reviewed, and their impact upon pregnancy is described. Although it is the most common cause of jaundice during pregnancy, viral hepatitis does not generally increase the risk of pregnancy complications, nor is it teratogenic. Vertical transmission of some types of viral hepatitis does occur, however.

Mouse hepatitis viral infection induces an extrathymic differentiation of the specific intrahepatic alpha beta-TCRintermediate LFA-1high T-cell population.

Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent model for the study of thymic and extrathymic T-cell subpopulation disorders induced during viral hepatitis. It was recently reported that, in addition to the intrathymic T-cell differentiation pathway, an extrathymic differentiation pathway of alpha beta-T-cell receptor (TCR) T lymphocytes exists in the liver, and becomes important under pathological situations such as autoimmune diseases, malignancies or hepatic bacterial infections. In the present study, we compared the phenotypes of resident hepatic, splenic or thymic T-cell subpopulations during the acute viral hepatitis induced by HMV3 in susceptible C57BL/6 mice. The number of liver-resident mononuclear cells (MNC) increased during the viral infection, while cellularity decreased. Single positive (SP) CD4+ cells strongly increased in both the liver and thymus, while double positive (DP) (CD4+ CD8+) cells, present in the liver and thymus of mock-infected mice, decreased in C57BL/6 mice during the viral infection. A shift of alpha beta-TCRintermediate T cells toward alpha beta-TCRhigh was evidenced in the liver and thymus of infected mice, but not in the spleen. The few alpha beta-TCRint double negative (DN) (CD4-CD8-) cells also decreased following viral infection. alpha beta-TCRint or high lymphocytes expressing high levels of leucocyte function antigen-1 (LFA-1) increased in the liver of MHV3-infected mice. In addition, liver-resident T cells expressed strongly the CD44 (Pgp-1) activation marker, suggesting that they were either activated or antigen experienced during the viral infection. No significant change in T-cell subpopulations was detected in the spleen, suggesting that MHV3 infection could induce an early in situ differentiation of resident hepatic T cells rather than a recruitment of lymphocytes from peripheral lymphoid organs.

Replication of murine coronaviruses in mouse embryonic stem cell lines in vitro.

Replication of murine coronaviruses in eight mouse embryonic stem (ES) cell lines of several genetic backgrounds was examined. Both mouse hepatitis virus (MHV) type 2 and MHV, strain A59 replicated well with no or minimal cytopathic effect in all the ES cell lines tested. The results suggest the possibility that MHV-infected ES cells may disseminate MHV in mouse colonies due to embryo manipulation.

POSTEXPOSURE PROPHYLAXIS

The timely facilitation of immunologic (immunoglobulin or vaccine) or antimicrobial prophylaxis is used in individuals who have been exposed to certain infectious diseases. Such methodology has been shown to be helpful in infections such as viral hepatitis types A and B, measles, varicella, rabies, and tuberculosis. The data supporting such use in rubella and mumps are not strong and information is still needed in hepatitis C, human immunodeficiency virus, and Lyme borreliosis. This article reviews postexposure prophylaxis in these situations. Preventive strategies for meningococcal disease, group A streptococcus, tetanus, diphtheria, and pertussis are discussed elsewhere in this issue.

Prevalence study of different hepatitis markers among pregnant Albanian refugees in Greece

Aim of the study was to record the prevalence of the various types of viral hepatitis, especially hepatitis B, in pregnant Albanian refugees in Greece. The study comprised 500 pregnant refugees of mean age 25.1 +/- 4.6 years. In Albania, all women had lived in overcrowded houses and had been exposed to non throw-away needles and syringes. Various indices for all hepatitis types were determined. The prevalence of HBsAg was 13.4%, of anti-HBs 53%, of total anti-HBc 70.8%, of anti-HBc IgM 0.4%, of HBeAg 1.2%, of anti-HBe 58.6%, of anti-HAV 96.2%, of anti-HAV IgM 1%, of anti-HDV 0.4%, of anti-HCV 0.6% and of anti-HEV 2%. HBeAg was found positive in 7.5% of HBsAg carriers. Prevalence of hepatitis B markers, as determined by HBsAg and/or anti-HBs and/or total anti-HBc was significantly higher in those with a history of previous hospitalization in Albania (p = 0.01) and those with previous history of hepatitis (p = 0.02). The high prevalence of hepatitis B markers in pregnant Albanian refugees proves that HBV infection is highly endemic in Albania and the possibility of perinatal transmission to the offsprings urges for HBV vaccination programmes. On the other hand improvements in the socioeconomic conditions and the sanitation system in Albania is anticipated to reduce the incidence of HAV and HBV infections.

Effect of adoptive transfer of CD4, CD8 and B cells on recovery from MHV3‐induced immunodeficiencies

A chronic viral infection can occur when the host fails to mount an effective immune response to clear the virus. Mouse hepatitis virus type 3 (MHV3) appears to be an excellent model for the study of the relationship between viral-induced immunodeficiency and chronic disease development. (C57BL/6 x A/J)F1 mice surviving acute hepatitis develop a chronic disease characterized by T- and B-cell immunodeficiencies, viral persistence in various organs including the brain, spleen and thymus, and death within 3 months postinfection (p.i.). We have reported that T- or B-cell deficiencies, observed in MHV3 chronically infected (C57BL/6 x A/J)F1 mice, can be partially or totally thwarted by adoptive transfer of CD4+, CD8+ and/or B cells, at 15 days p.i. in mice surviving the acute phase of the disease. Adoptive transfer of syngeneic CD4+ and/or CD8+ allowed a partial restoration of the T-cell deficiencies, as characterized by thymic atrophy, decrease in splenic T cells, and in all thymocyte subpopulations. B-cell immunodeficiency, as defined by a decrease in splenic B cells, as well as in the bone marrow pre-B- and B-cell compartments, and the occurrence of abnormally larger forms of bone marrow pre-B and B cells, were partially thwarted by B-cell treatment only. Splenic B cells and the bone marrow B-cell compartment, respectively, returned partially or totally to normal values, whereas the pre-B-cell compartment remained depleted in infected mice treated with B cells. Levels of all immunoglobulin classes returned to normal values in MHV3 chronically infected mice when treated with CD4+ in combination with CD8+ cells. All T- and/or B-cell treatments, however, were sufficient to thwart the process of the chronic disease, and favoured the survival of mice for up to 6 months p.i.

Seroepidemiology of HBV/HCV in Pakistan

Pakistan is an endemic country for all types of human hepatitis viruses. Their geographical prevalence depends on the ethnicity of population in various areas and their cultural and religious practices. Major etiological factors are faulty injection/transfusion practices, quackery and bad hygienic habits. This paper presents cumulative data of HBV/HCV in various groups. Viral markers in all studies were done using EIA technique.

Serum hyaluronate in patients with acute and fulminant hepatitis.

We evaluated serum hyaluronate (HA) levels in 17 patients with acute hepatitis and 9 with fulminant hepatitis (FH). Upon admission, patients with FH showed increased levels of serum HA and these levels showed significant correlation with biochemical parameters such as human hepatocyte growth factor, hepaplastin test, and prothrombin activity. In patients with AH, the levels of serum HA decreased during convalescence. Higher serum HA levels were observed in patients with type A acute hepatitis than in patients with non-A type. In patients with FH, serum HA levels were decreased in the survivors, while they were elevated in the non-survivors. These findings suggest that serum HA levels may be a useful indicator for evaluating the prognosis of patients with acute and fulminant hepatitis. Further study is necessary to determine whether there is a causal relationship between elevated serum HA levels and the type of hepatitis virus.