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.     

HBV合并HCV或人类免疫缺陷病毒感染的抗病毒治疗进展

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染是目前全球慢性肝病的主要原因,HBV合并人类免疫缺陷病毒(HIV)感染也较常见,全球4000万HIV感染者中10%并发慢性乙型肝炎(CHB).自从高效抗逆转录病毒治疗的推广,艾滋病相关原因的死亡已经减少,但由肝脏疾病造成的死亡却不断上升,逐渐成为HIV感染者发病和死亡的一个主要原因.     

慢性丙型肝炎患者混合或重叠感染其他病原体状况分析

目的了解丙型肝炎病毒（HCV）感染者混合或重叠感染乙型肝炎病毒（HBV）、人免疫缺陷病毒（HIV）和梅毒螺旋体（TP）的状况,为HCV感染的防治提供依据。方法采用ELISA法检测乙型肝炎病毒标志物、抗TP和抗HIV;采用化学发光法检测抗HCV;采用蛋白印迹法确认HIV感染。结果在169例HCV感染者中,重叠感染HBV 25例（14.8%）、HIV 4例（2.4%）、TP 9例（5.3%）,重叠感染HBV和TP 2例（1.2%）,重叠感染HBV和HIV 2例（1.2%）;静脉吸毒者重叠感染HIV（6.7%）和TP（11.1%）的比例均明显高于非静脉吸毒者（P〈0.05）;男性患者重叠感染HBV的比例（19.7%）明显高于女性患者（3.8%,P〈0.01）,女性患者重叠感染TP的比例（11.5%）明显高于男性患者（2.6%,P〈0.05）。结论随着感染方式的多元化,慢性丙型肝炎患者重叠感染其他病原体的情况更加常见。     

Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City,United States

AIM： To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus （HIV）/hepatitis B virus （HBV）/hepatitis C virus （HCV） in an urban clinic population. METHODS： Retrospective chart review of 5639 patients followed at St. Luke＇s-Roosevelt Hospital HIV Clinic （Center for Comprehensive Care） in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed： age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. RESULTS： HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 （4.47%）, 1411/5639 （25.02%） and 89/5639 （1.58%） patients, respectively. HIV/HBV co-infections were associated with male gender （OR 1.711; P = 0.005）, black race （OR 2.091, P 〈 0.001）, men having sex with men （MSM） （OR 1.747, P = 0.001）, intravenous drug use （IDU） （OR 0.114, P 〈 0.001）, IDU and heterosexual activity （OR 0.247; P = 0.018）, or unknown （OR 1.984, P = 0.004）.HIV/HCV co-infections were associated with male gender （OR 1.241; P = 0.011）, black race （OR 0.788; P = 0.036）, MSM （OR 0.565; P 〈 0.001）, IDU （OR 8.956; P 〈 0.001）, IDU and heterosexual activity （OR 9.106; P 〈 0.001）, IDU and MSM （OR 9.179; P 〈 0.001）, or transfusion （OR 3.224; P 〈 0.001）. HIV/HBV/HCV coinfections were associated with male gender （OR 2.156; P = 0.015）, IDU （OR 6.345; P 〈 0.001）, IDU and heterosexual activity （OR 9.731; P 〈 0.001）, IDU and MSM （OR 9.228; P 〈 0.001）, or unknown （OR 4.219; P = 0.007）. CONCLUSION： Our study demonstrates that coinfection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.     

Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation

Hepatitis B virus, hepatitis C virus and human immunodeficiency virus share a similar transmission pathway and are often diagnosed in the same patient. These patients tend to have a faster progression of hepatic fibrosis. This cross-sectional study describes the demographic features and clinical profile of human immunodeficiency virus/hepatitis co-infected patients in Paraná, Southern Brazil. A total of 93 human immunodeficiency virus-infected patients attending a tertiary care academic hospital in Southern Brazil were included. Clinical, demographic and epidemiological data were evaluated. Hepatitis B virus and/or hepatitis C virus positive serology was found in 6.6% of patients. The anti-hepatitis C virus serum test was positive in 85% (79/93) of patients, and the infection was confirmed in 72% of the cases. Eighteen patients (19%) were human immunodeficiency virus/hepatitis B virus positive (detectable HBsAg). Among co-infected patients, there was a high frequency of drug use, and investigations for the detection of co-infection were conducted late. A low number of patients were eligible for treatment and, although the response to antiretroviral therapy was good, there was a very poor response to hepatitis therapy. Our preliminary findings indicate the need for protocols aimed at systematic investigation of hepatitis B virus and hepatitis C virus in human immunodeficiency virus-infected patients, thus allowing for early detection and treatment of co-infected patients.     

Seroprevalence of HCV and its co-infection with HBV and HIV among liver disease patients of South Tamil Nadu

AIM: To determine the seroprevalence of hepatitis C virus (HCV) and its co-infection with hepatitis B virus (HBV), hepatitis delta agent (HDV) and human immunodeficiency virus (HIV) among liver disease patients of south Tamil Nadu.METHODS: A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus (anti HCV and HCV RNA), Hepatitis B virus (HBsAg), Hepatitis delta agent (anti HDV) and Human immuno virus (antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits. HCV RNA was detected by RT-PCR. Liver function tests like ALT, AST, GGT, ALP, bilirubin and albumin were also studied.RESULTS: The seroprevalence of HCV was found to be 5.6% among liver disease patients by ELISA. 27/512, 49/512 and 12/512 patients were positive for HIV, HBV & HDV respectively. Co-infection of HCV & HBV was found in 8 patients, with 6 for HCV & HIV and 4 for HCV, HBV & HIV co-infections. Sex-wise analysis showed that HIV, HCV & HBV and HCV & HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1 ± 8.3 and 49 ± 10.1. In people co-infected with HCV & HBV or HCV & HIV or HCV, HBV & HIV the mean ALT of 58.0 ± 03.16, 56.78 ± 4.401 and 64.37 ± 4.01 respectively.CONCLUSION: We strongly recommend routine test of the blood for HCV in addition to HBV and HIV. We also recommend individualized counseling to identify those at risk and testing for those who want it. Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.     

Expanding the donor pool: Hepatitis C,hepatitis B and human immunodeficiency virus-positive donors in liver transplantation

Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Hepatitis B and C infection and liver disease trends among human immunodeficiency virus-infected individuals

AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and he...     

Coinfection of hepatitis B and hepatitis C virus in HIV-infected patients in south India

AIM To screen for the co-infection of hepatitis B (HBV)and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients insouthern India.METHODS Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA)using commercially available ELISA kits; HBsAg, HBeAg/anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV.RESULTS HBV co-infection was detected in 45/500 (9%)patients and HCV co-infection in 11/500 (2.2%) subjects.Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55%(22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6(54.5%) were anti-HCV and HCV RNA positive, while 3(27.2%) were positive for anti-HCV alone and 2 (18%)were positive for HCV RNA alone.CONCLUSION Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients.Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

广东省单纯丙型肝炎病毒及其与人类免疫缺陷病毒共感染者丙型肝炎病毒的基因亚型分析

目的 了解广东省人类免疫缺陷病毒(HW) /HCV共感染者与单纯HCV感染者的感染途径、HCV的基因亚型分布及其遗传特征,为丙型肝炎病毒感染的治疗与预防提供依据. 方法采用巢式逆转录-聚合酶链反应扩增广东省95例HIV/HCV共感染者及99例单纯HCV感染者HCVNS5B基因区域,扩增产物测序后进行HCV基因亚型分析,遗传分析利用MEGA4软件.不同种基因亚型型内基因距离以碱基置换率表示.结果 HIV/HCV共感染者HCV有5种基因亚型,其中6a型占53.7％ (51/95)、3a型占17.9％ (17/95)、1b型占15.8％ (15/95)、3b型占11.6％ (11/95)、1a型占1.0％(1/95);1b亚型内基因距离为6.30％±1.27％,高于其他基因亚型.HIV/HCV共感染者主要通过静脉注射毒品感染(75/95,78.9％),其基因亚型主要为6a型,占60.0％ (45/75).单纯HCV感染者HCV有7种基因亚型,其中1b型占67.7％ (67/99)、6a型占17.2％(17/99)、3a型占6.1％ (6/99)、2a型占5.％(5/99)、3b型占2.0％(2/99)、4a型占1.0％ (1/99)、5a型占1.0％(1/99);1b亚型内基因距离为5.17％±1.03％,高于其他基因亚型.单纯HCV感染者主要通过输血或血液制品感染(80/99,80.8％),其HCV基因亚型主要为1b型,占76.2％ (61/80).结论 广东地区HIV/HCV共感染者及单纯HCV感染者HCV基因亚型呈现多样性,HIV/HCV共感染者与单纯HCV感染者主要感染途径不同,HCV主要基因亚型也不同.     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

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…     

Management of hepatitis C virus infection in HIV/HCV co-infected patients： Clinical review

Nearly one fourth of individuals with human immunodeficiency virus （HIV） infection have hepatitis C virus （HCV） infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti- HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection （33% vs 72%, P = 0.07）. A betterunderstanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome, and survival.     

Cross-sectional epidemiology of hepatitis C virus detection and treatment in HIV-infected patients

Background

Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients.

Methods

Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines.

Results

We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n = 12) or having hepatitis C virus RNA not detectable (n = 9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n = 22), provider barriers (n = 15), or patient barriers (n = 40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p = 0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p = 0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers.

Conclusion

A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.     

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...     

Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users

Background/Aim: This retrospective study aimed to better define the respective biological and pathological impact of human immunodeficiency virus infection and chronic alcohol consumption on the course of hepatitis C virus infection in intravenous drug users.Methods: Two hundred and ten consecutive anti-HCV positive intravenous drugs users, among whom 60 were also anti-HIV positive, took part in the study at the University Hospital, Paris, France.Results: The activity of aspartate aminotransferase and gamma-glutamyl transpeptidase was significantly increased in serum from anti-HIV positive patients. The mean hepatitis activity index was significantly higher in anti-HIV positive patients (p<0.05), among whom there was also a higher proportion of patients with cirrhosis as compared to anti-HIV negative patients (30.0 vs 15.3%, p<0.0001). Excessive alcohol drinking (recorded in around 35% of the patients, whatever their HIV status), as compared to non-excessive drinking, was more often associated with cirrhosis in anti-HIV negative (24.5 vs 11.3%, p<0.05) than in anti-HIV positive patients (30.4 vs 29.7%, not significantly). In a multivariate analysis, HIV infection (relative risk 2.2, confidence interval 1.1–4.5) and excessive alcohol drinking (relative risk 1.9, confidence interval 1.0–3.9) were the variables independently associated with the risk of cirrhosis.Conclusion: Human immunodeficiency virus infection worsens the course of chronic hepatitis C in intravenous drug users. Excessive alcohol drinking also appears to be a crucial negative cofactor, and therefore alcohol withdrawal should be proposed as an integral part of the therapy.     

Seroprevalence of hepatitis E virus in chronic hepatitis C in Brazil

Background and aims

Hepatitis E virus infection in patients with underlying chronic liver disease is associated with liver decompensation and increased lethality. The seroprevalence of hepatitis E virus in patients with chronic hepatitis C in Brazil is unknown. This study aims to estimate the seroprevalence of hepatitis E virus in patients with chronic hepatitis C and to describe associated risk factors.