A case of HIV co-infected with hepatitis B virus precore/core deletion mutant treated by entecavir.

We report a case of a HIV and hepatitis B virus (HBV)-co-infected patient to whom entecavir (ETV) was administered initially before the notification regarding the potential mutagenesis effect on HIV against the nucleoside analog. Since initial evaluations indicated the advanced stage of chronic hepatitis B and preserved numbers of peripheral CD4+ lymphocytes without the manifestation of immunodeficiency, priority was given to the management of HBV. We started HBV therapy with ETV at a dose of 0.5 mg daily without using any HIV drugs. The viral loads of both HBV and HIV-1 decreased gradually during the 5 months following the initial administration of ETV. HBV was well controlled by the gradual replacement of ETV with highly-active antiretroviral therapy against HIV with a regimen including atazanavir, emtricitabine, and tenofovir. HBV was genotyped as A2 with the quasispecies pool consisting of the -1G precore/core deletion mutant strain.     

某医院HIV感染者中HBV HCV TP混合感染状况分析

目的 了解综合性医院首诊艾滋病病毒(HIV)感染者中合并乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)和梅毒螺旋体(TP)的混合感染情况及临床特点,为艾滋病(AIDS)的防控和治疗提供科学依据.方法 2013年1月至2017年12月,以非艾滋病首诊于某综合性医院而确证为HIV感染者,收集其人口学资料和临床资料,并进行乙...     

HIV/hepatitis C virus and HIV/hepatitis B virus coinfections protect against antiretroviral-related hyperlipidaemia

Introduction

Hyperlipidaemia is a recognized complication of HIV antiretroviral therapy. The interactions among HIV, viral hepatitis, antiretroviral therapies and lipids are poorly understood.

Methods

Ontario HIV Treatment Network Cohort Study participants with at least one lipid level after highly active antiretroviral therapy (HAART) initiation were assessed. Hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐coinfected patients were identified by serology or chart review. HCV antiviral recipients, diabetics and those on lipid‐lowering drugs at baseline were excluded from the study. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use were assessed by multivariate logistic regression.

Results

A total of 1587 HIV‐monoinfected, 190 HIV/HBV‐coinfected and 255 HIV/HCV‐coinfected patients were evaluated. Most were male (85–92% for the 3 groups evaluated: HIV, HIV/HBV, HIV/HCV). The median [interquartile range (IQR)] age at HAART initiation was 48 (44–56) years and was similar between groups. The median (IQR) CD4 count at HAART initiation was 245 (120–370) cells/μL in HIV‐monoinfected participants, 195 (110–330) cells/μL in HIV/HBV‐coinfected participants and 268 (140–409) cells/μL in HIV/HCV‐coinfected participants. Factors associated with a decreased risk of grade 3 or 4 hyperlipidaemia or lipid‐lowering drug use included HIV/HCV coinfection [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.34, 0.61; P<0.0001], HIV/HBV coinfection (OR 0.74; 95% CI 0.55, 0.99; P=0.04), year of starting HAART after 2004 vs. 1997 or earlier (OR 0.37; 95% CI 0.29, 0.48; P<0.0001) and year of starting HAART between 1998 and 2003 vs. 1997 or earlier (OR 0.75; 95% CI 0.61, 0.92; P<0.01). Factors associated with increased risk included age (OR 1.55; 95% CI 1.39, 1.72; per 10 years, P<0.0001) and male gender (OR 1.84; 95% CI 1.36, 2.48; P<0.0001).

Conclusions

HIV/HCV and to a lesser extent HIV/HBV coinfections are protective against HAART‐related hyperlipidaemia.     

The rate of treatment of chronic hepatitis C in patients co-infected with HIV in an urban medical centre

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is common. HIV co-infection results in a higher rate of histologic progression and shorter interval to HCV-related cirrhosis. Successful treatment of HCV with interferon-based therapy reduces the morbidity and mortality of patients. Significant factors may limit the availability of treatment in co-infected patients. The rate of treatment of HCV and limiting factors to treatment in a co-infected population in an urban setting were determined. A retrospective review of co-infected patients was conducted at our liver and gastrointestinal (GI) clinics for treatment of HCV from July 2001 to June 2002. Treatment of HCV and reasons for nontreatment were recorded. A total of 104 HCV/HIV co-infected patients were identified. Seventy-two per cent were males. Mean age was 47.2 years (32-72). Seventy-four of the 82 (90%) with identifiable risk factors for HCV infection had a history of intravenous drug use (IVDU). Twenty per cent (21/104) of the total underwent a liver biopsy. Sixty-seven per cent who had a liver biopsy were treated. Overall, sixteen patients were treated. Eighty-eight (85%) patients were not treated for the following reasons: 13 refused treatment, and 75 were ineligible. Of the ineligible patients, 40% were noncompliant with visits, 15% were active substance abusers, 13% had decompensated cirrhosis, 8% had significant active psychiatric conditions and 24% had significant co-morbid disease. A majority of patients co-infected with HCV/HIV had a IVDU history. Most co-infected patients were not eligible for HCV treatment. A majority of noncandidates had potentially modifiable psychosocial factors leading to nontreatment.     

Prevalence of hepatitis B virus infection in Japanese patients with HIV.

Patients with HIV infection are frequently infected with hepatitis viruses, which are presently the major cause of mortality in HIV-infected patients after the widespread use of highly active antiretrovirus therapy. We previously reported that approximately 20% of HIV-positive Japanese patients were also infected with hepatitis C virus (HCV). Hepatitis B virus (HBV) infection may also be an impediment to a good course of treatment for HIV-infected patients, because of recurrent liver injuries and a common effectiveness of some anti-HIV drugs on HBV replication. However, the status of co-infection with HIV and HBV in Japan is unclear. We conducted a nationwide survey to determine the prevalence of HIV-HBV co-infection by distributing a questionnaire to the hospitals belonging to the HIV/AIDS Network of Japan. Among the 5998patients reported to be HIV positive, 377 (6.4%) were positive for the hepatitis B surface antigen. Homosexual men accounted for two-thirds (70.8%) of the HIV-HBV co-infected patients, distinct from HIV-HCV co-infection in Japan in which most of the HIV-HCV co-infected patients were recipients of blood products. One-third of HIV-HBV co-infected patients had elevated serum alanine aminotransferase levels at least once during the 1-year observation period. In conclusion, some HIV-infected Japanese patients also have HBV infection and liver disease. A detailed analysis of the progression and activity of liver disease in co-infected patients is needed.     

Current treatment options for hepatitis C patients co-infected with HIV

With the availability of all-oral, direct acting antivirals (DAAs), hepatitis C virus (HCV) therapy has been revolutionized for HIV/HCV co-infected patients. Indeed HCV cure rates are now no longer different between HCV mono and HIV/HCV co-infected persons and are both greater than 95%. Therefore, current treatment guidelines no longer separate these two groups. Indications for HCV treatment and choice of DAA combination are now the same for all HCV patients. In HIV/HCV co-infection however, drug interactions between HIV and HCV agents need be checked prior to starting HCV therapy. Finally, the higher risk of hepatic decompensation in HIV/HCV co-infected patients, including those receiving successful antiretroviral therapy, continues to make these patients a high priority group for receiving access to modern DAA combination therapy.     

人类免疫缺陷病毒/丙型肝炎病毒混合感染者抗丙型肝炎病毒治疗的进展

由于人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）有相同的传播途径,HIV/HCV混合感染现象十分普遍,已成为严重的公共卫生问题。高效抗逆转录病毒治疗（HAART）的应用显著减少了与HIV感染相关的发病率和病死率,而HCV混合感染引起的慢性肝脏疾病日益成为HIV/HCV混合感染者发病和死亡的重要因素。HIV/HCV混合感染者HCV相关肝病的风险增加,有效的抗HCV治疗对延长这一人群的生存期至关重要。本文就抗HCV治疗对象的评估、治疗时机的选择、治疗的方法、治疗监测和疗效评估以及治疗注意的问题作一综述。     

Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus

Summary  Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV–HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV–HCV (39.7, 4.1); 12 HBV–HDV (35.2, 9.9); 12 HBV–HCV–HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13–13.10, P  =   0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03–6.81, P  =   0.04), but marginally associated with HIV–HBV–HCV–HDV (aOR = 2.32, 95%CI 0.94–5.74, P  =   0.07). In quad-infection, lower HDV-undetectability ( vs HIV–HBV–HDV, P  =   0.2) and higher HCV-undetectability ( vs HIV–HBV–HCV, P  =   0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up ( vs HIV–HBV co-infection): HIV–HBV–HCV = 2.23–5.67, HIV–HBV–HDV = 1.53–15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.     

Pretreatment assessment and predictors of hepatitis C virus treatment in US veterans coinfected with HIV and hepatitis C virus

The US Department of Veterans Affairs (VA) cares for many human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients. VA treatment recommendations indicate that all HIV/HCV-coinfected patients undergo evaluation for HCV treatment and list pretreatment assessment tests. We compared clinical practice with these recommendations. We identified 377 HIV/HCV-coinfected veterans who began HCV therapy with pegylated interferon and ribavirin and 4135 HIV/HCV-coinfected veterans who did not but were in VA care at the same facilities during the same period. We compared laboratory and clinical characteristics of the two groups and estimated multivariate logistic regression models of receipt of HCV treatment. Overall, patients had high rates of receipt of tests necessary for HCV pretreatment assessment. Patients starting HCV treatment had higher alanine aminotransferase (ALT), lower creatinine, higher CD4 counts and lower HIV viral loads than patients not starting HCV treatment. In the multivariate model, positive predictors of starting HCV treatment included being non-Hispanic whites, having higher ALTs, lower creatinines, higher HCV viral loads, higher CD4 counts, undetectable HIV viral loads and receiving HIV antiretrovirals. A history of chronic mental illness and a history of hard drug use were negative predictors. Most HIV/HCV-coinfected patients received the necessary HCV pretreatment assessments, although rates of screening for hepatitis A and B immunity can be improved. Having well-controlled HIV disease is by far the most important modifiable factor affecting the receipt of HCV treatment. More research is needed to determine if the observed racial differences in starting HCV treatment reflect biological differences, provider behaviour or patient preference.     

Current treatment of HIV/hepatitis B virus coinfection

Coinfection with HIV and hepatitis B virus (HBV) has become a significant global health problem. Liver disease is now one of the leading causes of morbidity and mortality in individuals with HIV, particularly those with viral hepatitis. There are a number of agents available with dual activity against HIV and HBV, and effective treatment depends on understanding the potential advantages and pitfalls in using these agents. There are a number of unresolved issues in the management of HIV/HBV coinfection. These include the role of liver biopsy, the significance of normal aminotransferase levels, serum HBV DNA threshold for treatment, treatment end-points, and the treatment of HBV when HIV does not yet require treatment. Treatment of HBV should be considered in individuals with HIV/HBV coinfection with evidence of significant fibrosis (>/=F2), or with elevated serum HBV DNA levels (>2000 IU/mL). Sustained suppression of serum HBV DNA to below the level of detection by the most sensitive available assay should be the goal of therapy, and, at present, treatment of HBV in HIV/HBV coinfection is lifelong. If antiretroviral therapy is required, then two agents with anti-HBV activity should be incorporated into the regimen. If antiretroviral therapy is not required, then the options are pegylated interferon, adefovir or the early introduction of antiretroviral therapy. Close monitoring is necessary to detect treatment failure or hepatic flares, such as immune reconstitution disease. Further studies of newer anti-HBV agents in individuals HIV/HBV coinfection may advance treatment of this important condition.     

HBV感染者HCV的重叠感染关系研究

目的 研究HBV感染患者中HCV的重叠感染状况及其相互关系。 方法 采用ELISA法对767例HBV感染患者同步检测HBV和HCV血清标志物,对可疑HCV感染但抗HCV阴性和/或抗-HCV阳性患者血清,采用PCR法检测HCV-RNA。 结果 HCV重叠感染率为4.82％,且在各类乙肝患者中存在非常显著差异(P<0.01);HBV/HCV感染组重症肝炎的发生率显著高于非HCV感染组(P<0.01);HBV/HCV感染组HBsAg阳性率显著低于单纯HBV感染组(P<0.05);HBV/HCV感染组HCV-RNA阳性率显著低于单纯HCV感染组(P<0.05)。 结论 HCV重叠感染与乙肝患者的发病、病情加重及重症肝炎的发生相关;HCV可抑制或中止HBsAg携带状态,但这种作用远不如对病情的加重作用重要;同时HBV对HCV的复制亦存在抑制作用。     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Pruritus in patients with chronic human immunodeficiency virus, hepatitis B and C virus infections

AIM: The prevalence of pruritus was prospectively determined in 310 patients of whom 119 had hepatitis C virus infection, 91 hepatitis C virus and human immunodeficiency virus, 51 human immunodeficiency virus infection alone, 31 hepatitis B virus and human immunodeficiency virus coinfection and 18 were HBsAg carriers. RESULTS: Patients in the first three groups were more likely to complain of itching (22%, 28% and 25%, respectively) than HBsAg carriers (8.2%, p=0.01. Laboratory data were not different between groups, except for the human immunodeficiency virus group, whose alkaline phosphatase levels were highest, and CD4 counts were lowest (median 30 cells/mm3). Patients with hepatitis C, including those with human immunodeficiency virus, had similar hepatitis C virus RNA levels in patients with or without pruritus. There was no difference in hepatic inflammation or fibrosis between those with and those without pruritus. CONCLUSION: 20% of patients with chronic hepatitis C and 8% of hepatitis B patients complain of pruritus. Patients with pruritus have laboratory and histologic parameters comparable to those without.     

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.