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Hepatitis B and Human Immunodeficiency Virus Coinfection Featured

Coinfection with human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) is common; worldwide, an estimated 10% of HIV-infected persons have chronic hepatitis B.

Because the incidence of traditional acquired immunodeficiency syndrome–related opportunistic infections has decreased with successful anti-HIV therapy, liver disease has emerged as a leading cause of morbidity and mortality in HIV-infected individuals. HIV infection negatively impacts all phases of the natural history of hepatitis B leading to increased rates of persistent infection, higher HBV DNA levels, lower rates of hepatitis B e antigen loss, increased cirrhosis and liver-related mortality, and increased risk of hepatocellular carcinoma at lower CD4 T cell counts. The management of hepatitis B in HIV infection is complicated by the dual activity of several nucleoside analogs, the more rapid development of lamivudine-resistant HBV in patients who are HIV-positive, and the paucity of studies in this population. Until further research emerges on the optimal treatment for this population, data from HBV monoinfected persons will need to be extrapolated to the HIV-HBV coinfected population. Further research is also needed to determine the mechanism(s) for the increased liver disease progression and optimal treatment goals.

(Chloe L. Thio - HEPATOLOGY 2009;49: S138-S145.)

Introduction

Both human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) are transmitted through sexual and percutaneous routes; thus, coinfection with both viruses is common.1 Worldwide, it is estimated that 10% of the 40 million HIV-infected individuals have chronic hepatitis B.2 Since the introduction of highly active antiretroviral therapy (HAART) in the United States and other industrialized countries, deaths from AIDS-related causes have declined, but liver disease has emerged as one of the leading causes of morbidity and mortality.3,4 As HAART is introduced into areas of the world with high HBV endemicity, hepatitis B–related liver disease is expected to increase in the HIV-infected population; thus, it is important to understand the interaction of these two chronic viral infections. Management of hepatitis B in patients infected with HIV is complicated not only by the differences in natural history but also by other issues such as the activity of several drugs against both viruses and development of drug-resistant HIV and HBV variants. In this review, the epidemiology, natural history, and management of hepatitis B in HIV-infected individuals will be discussed, highlighting differences from HBV monoinfected individuals.

Epidemiology

Coinfection with hepatitis B is common among HIVinfected individuals. The prevalence of HBV varies markedly among different HIV-infected populations, but one of the major determinants is geographical location. In areas with low HBV endemicity, such as the United States, Australia, and Europe, HBV and HIV are usually acquired in adulthood through either sexual or percutaneous transmission. HBV is 100-fold more likely to be transmitted than HIV,5 thus, HBV infection often precedes HIV infection. In these low endemicity areas, the prevalence of HBV coinfection is 5%-7% of HIV-infected individuals but varies depending on the route of infection.2 The highest prevalence of coinfection is 17%, and the lowest prevalence is from heterosexual transmission (Fig. 1). In countries with intermediate and high HBV endemicity, the principal routes of HBV transmission are perinatal or in early childhood; thus, HBV infection usually precedes HIV infection by decades. In these countries, the majority of studies show HBV coinfection prevalence of 10%-20%,6-8 but some show prevalence rates as low as 6%.

Natural History

HIV adversely affects all phases of the natural history of adult-acquired hepatitis B (Table 1). After HBV infection, HIV-infected individuals are up to six-fold more likely to develop chronic hepatitis B than are HIV-negative individuals.10,11 Bodsworth et al. retrospectively studied 77 men who acquired HBV infection, of whom 31 were HIV-infected prior to HBV infection.10 Of the HIV-infected men, 23% developed chronic hepatitis B compared to 4% of the HIV-uninfected men (P 0.03). Of note, the mean CD4 T cell counts were lower in the HIV-infected men who developed chronic hepatitis B compared to the HIV-infected men who did not become chronically infected. HIV infection also decreases the rate of hepatitis B e antigen (HBeAg) clearance up to five-fold and increases the level of HBV replication as manifested by higher HBV DNA levels.12-14 Even HIV-infected persons who acquire protective antibody to hepatitis B surface antigen (anti-HBs) remain at risk for loss of anti-HBs and subsequent reactivation of HBV (reverse seroconversion).15,16 Of all these negative consequences, the most important is that HIV accelerates the progression of HBV-related liver disease. Cirrhosis is more common in HIV-HBV coinfection despite lower alanine aminotransferase (ALT) levels than in HBV monoinfection,12 and may be related to lower CD4 T cell counts.17 Thio et al. found that HIV coinfection impacted liver-related mortality in an analysis of 5293 men of whom 326 were positive for hepatitis B surface antigen (HBsAg).18 The HIV-HBV coinfected men were over 17 times more likely to die of liver-related causes compared to those monoinfected with HBV. One unanswered question on the natural history of HBV is the effect of HIV coinfection on development of hepatocellular carcinoma (HCC). There is some evidence that lower CD4 T cell counts are associated with increased risk for HCC in HIVHBV coinfected individuals,19 but whether HIV in general increases the risk is not known. All of the natural history studies cited here were conducted in areas of the world where HBV is acquired in adulthood; thus, it is unknown whether the effects of HIV are the same when HIV is acquired years after a chronic hepatitis B infection is established, as in countries with high HBV endemicity.

Pathogenesis of Liver Disease

Diagnosis of Hepatitis B in HIV Infection

Management of Chronic Hepatitis B

Needs for Future Research

References

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Last modified on Thứ năm, 15 Tháng 10 2020 03:27
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