Clinical significance of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role...     

Role of occult hepatitis B virus infection in chronic hepatitis C

The development of sensitive assays to detect small amounts of hepatitis B virus(HBV) DNA has favored the identification of occult hepatitis B infection(OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV(HBs Ag) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody(antiHBc) in serum of HBs Ag-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C(CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma(HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC.     

Occult hepatitis B virus infection: A major concern in HIV-infected patients: Occult HBV in HIV

Human immunodeficiency virus (HIV)- infected patients are at risk of acquiring viral hepatitis, due to common routes of transmission. As the introduction of highly active antiretroviral therapy (HAART) reduced the frequency of opportunistic infections and improved survival, viral hepatitis emerged as an important cause of morbidity and mortality in HIV-infected cases. Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg). There are conflicting reports on the impact of occult HBV infection on the natural history of HIV disease. In this review, we described the findings of studies on HIV and hepatitis B co-infection with focus on the prevalence of occult HBV infection. The results of this review demonstrated the importance of prevention, diagnosis and treatment of occult HBV infection in HIV-positive patients.     

Occult hepatitis B virus and hepatocellular carcinoma

Occult hepatitis B virus (HBV) infection (OBI) is a challenging pathobiological and clinical issue that has been widely debated for several decades. By definition, OBI is characterized by the persistence of HBV DNA in the liver tissue (and in some cases also in the serum) in the absence of circulating HBV surface antigen (HBsAg). Many epidemiological and molecular studies have indicated that OBI is an important risk factor for hepatocellular carcinoma (HCC) development. OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection. Indeed, in OBI as in HBV-positive infection, HBV DNA can persist in the hepatocytes both integrated into the host genome as well as free episome, and may maintain the capacity to produce proteins-mainly X protein and truncated preS-S protein - provided with potential transforming properties. Furthermore, OBI may indirectly favor HCC development. It has been shown that the persistence of very low viral replicative activity during OBI may induce mild liver necro-inflammation continuing for life, and substantial clinical evidence indicates that OBI can accelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for HCC development.     

Occult hepatitis B virus infection in Egypt

The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.     

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.     

Occult Hepatitis B Virus Infection: An Update

Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host’s immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the “overt” infection, favoring the development of hepatocellular carcinoma.     

HBV and HIV co-infection:Impact on liver pathobiology and therapeutic approaches

The consequences of hepatitis B virus(HBV) and human immunodeficiency virus(HIV) co-infection on progression of severe liver diseases is a serious public health issue,worldwide. In the co-infection cases,about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals,liverrelated mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIVinduced liver diseases includes hepatitis,steatohepatitis,endothelialitis,necrosis,granulomatosis,cirrhosis andcarcinoma. Moreover,HIV co-infection significantly alters the natural history of hepatitis B,and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology,only a few data is available on interactions between HBV and HIV proteins. Thus,the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms,and to design effective therapeutic strategies.     

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence...     

Current practice and recommendations for management of hepatitis B virus in people living with HIV in Asia

Background

The prevalence of HIV and hepatitis B virus (HBV) co-infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. Important routes of transmission of both these infections include high-risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV-induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV.

Objectives

This article describes the prevalence of co-infection, current clinical practice, and recommendations for the management of people living with HIV-HBV co-infection in Asia.

Results and Conclusions

Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV-HBV co-infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co-infection rates. Mother-to-child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.     

Occult hepatitis B virus infection

Occult hepatitis B virus(HBV)infection(OBI)refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen.Since OBI was first described in the late 1970s,there has been increasing interest in this topic.The prevalence of OBI varies according to the different endemicity of HBV infection,cohort characteristics,and sensitivity and specificity of the methods used for detection.Although the exact mechanism of OBI has not been proved,intrahepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause.OBI has important clinical significance in several conditions.First,OBI can be transmitted through transfusion,organ transplantation including orthotopic liver transplantation,or hemodialysis.Donor screening before blood transfusion,prophylaxis for high-risk organ transplantation recipients,and dialysis-specific infection-control programs should be considered to reduce the risk of transmission.Second,OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy.Close HBV DNA monitoring and timely antiviral treatment canprevent HBV reactivation and consequent clinical deterioration.Third,OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C.Finally,OBI seems to be a risk factor for hepatocellular carcinoma by its direct protooncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis.However,this needs further investigation.We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.     

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.     

Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.     

HBV/HCV重叠感染的抗病毒治疗

从全球范围看,乙型肝炎病毒(hepatitis B virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)重叠感染估计约有700-2000万人口感染.重叠感染和单一HBV或HCV感染比较,更易发展为肝硬化、肝细胞癌甚至肝衰竭的比例也高,HBV和HCV重叠感染可有四种不同的临床模式,即HCV活动...     

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.     

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

INTRODUCTION Diseases of the hepatobiliary system are a major problem in patients with human immunodeficiency virus (HIV) infection. An estimated one-third of deaths in HIV patients are directly or indirectly related to liver disease. Liver diseases in HI…     

Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems.     

Occult Hepatitis B and Other Unexplored Risk Factors for Hepatocellular Carcinoma in Latin America

Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (< 200 IU/mL) in HBsAg-negative patients with or without serologic markers of previous viral exposure. The clinical significance of OBI is of concern in post-transfusional hepatitis B infection, hepatitis B reactivation, chronic liver disease and hepatocellular carcinoma (HCC). The diagnosis of OBI relays on the use of highly sensitive and specific laboratory techniques. Herein, comments derived from a study analyzing the frequency and characteristics of OBI in HCC Japanese patients are stated. While OBI and other causes of HCC have been highly studied in Asia and Europe, research in Latin America in these topics is limited. Several findings such as population risk groups with high prevalence of overt and OBI infection, HBV genotype F in Argentinean HCC patients, and the clinical impact of the foreign A-D genotypes suggest the need of further investigation. Additionally, alcoholism, obesity, NASH and type 2 diabetes may override the presence of OBI. Therefore, OBI diagnosis is essential. It is known that anti-HBc alone is a predictive signal of potential OBI and given the fluctuations of the HBV infection markers, testing for HBsAg and anti-HBc at baseline and follow-up is recommended. In conclusion, OBI and other causes involved in the epidemiology of HCC in Latin America are unexplored risk factors. Genome-based research is required to decipher the role of gene-environmental interactions associated with chronic liver disease. Novel algorithms to detect OBI supported by basic/applied/clinical research are also needed.     

Clinical implications of HIV and hepatitis B co-infection in Asia and Africa

Hepatitis B virus (HBV) is the leading cause of chronic liver disease and liver-related death worldwide, with the majority of these cases occurring in areas of Africa and Asia where HBV prevalence is high. Many of the countries that are affected by hepatitis B are also affected by a high HIV burden, leading to frequent HIV/HBV co-infection. The consequences of co-infection, including increased liver-related morbidity and mortality, increased hepatitis B viral replication, immune reconstitution to HBV in the setting of antiretroviral therapy, and hepatotoxicity from antiretroviral drugs, are especially important in regions with expanding antiretroviral programmes. Little data, however, are available on HIV/HBV co-infection from regions with high chronic hepatitis B prevalence. This Review discusses the epidemiology, natural history, pathogenesis, and management of HIV/HBV co-infection from these areas. Topics for future research relevant to HIV/HBV co-infection in Africa and Asia are also highlighted.