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.     

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.     

Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol

BACKGROUND/AIMS: We analyzed the characteristics of HIV infected patients who died from liver disease, focusing on hepatitis virus co-infection. METHODS: One-hundred and eighty-five French hospital departments involved in HIV/AIDS management prospectively notified all deaths occurring in 2000. Patients whose hepatitis C (HCV) and hepatitis B (HBV) serostatus was known were classified as being infected by HCV alone, HBV alone (HBsAg positive), both HCV and HBV, or neither HCB nor HBV. RESULTS: Among 822 HIV infected patients, 29% were infected by HCV alone, 8% by HBV alone, and 4% by both HCV and HBV. The most frequent causes of death were liver disease (31% of cases) and AIDS (29%) among HIV-HCV co-infected patients, and AIDS (38%) and liver disease (22%) among HIV-HBV co-infected patients. Liver disease was a more frequent cause of death among patients co-infected by both HCV and HBV (44% of cases). Hepatocellular carcinoma was present in 15% of patients who died from liver disease, and was associated with HBV co-infection. Nearly half the patients who died from liver disease had more than 200 CD4/mm3. CONCLUSIONS: Liver disease is now a leading cause of death among HIV-HCV co-infected patients and is becoming an important cause of death among HIV-HBV co-infected patients. The risk of death from liver disease is highest in patients co-infected by both HCV and HBV.     

Hepatitis B virus infection: co-infection with hepatitis C virus, hepatitis D virus, and human immunodeficiency virus

Hepatitis B virus (HBV) shares routes of transmission, namely exchange of infected body fluids, sharing of contaminated needles, and blood transfusion, with other hepatotropic viruses, such as hepatitis C virus (HCV) and hepatitis D virus (HDV) and with systemic retroviral infections, such as the human immunodeficiency virus (HIV). Thus, many HBV infected patients are co-infected with other viral pathogens. Co-infection appears to increase the risk of progression of liver disease and may have important ramifications on choice of antiviral medication and treatment regimen. This article reviews the current knowledge of co-infection of HBV with HCV, HDV, and HIV.     

HIV/HCV co-infection: histopathologic findings, natural history, fibrosis, and impact of antiretroviral treatment: a review article.

Human immunodeficiency virus/hepatitis C virus (HIV/HCV) co-infection has emerged as a leading cause of liver morbidity in the last two decades. Liver failure is also frequently a cause of death in HIV/HCV co-infected patients. Highly active antiretroviral treatment (HAART) has revolutionized the HIV treatment, leading to a significantly decreased morbidity, prolonged survival, and an overall better outcome of HIV infection. Hepatotoxicity associated with antiretroviral treatment, however, has been recognized as one of the serious complications of the treatment. The effects of HIV infection on the natural history and progression of HCV-associated chronic liver disease that had been well documented in the pre-HAART treatment era have been changing, and there are now many indications that HIV/HCV co-infection should be recognized as an evolving and a challenging disease entity.     

Co-infection VIH-VHB au sud du Sahara : données épidémiologiques, cliniques et thérapeutiques

In sub-Saharan Africa, co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) has several characteristics, one of which is its high prevalence. The rate of HBV infection, however, appears to be similar in HIV-positive and HIV-negative individuals. In cases of co-infection, the prognosis is poorer because of the often-late detection of HVB infection (screening for co-infection is not systematic) at an advanced stage of HIV infection, when antiretroviral therapy (HAART) has already been started. The difficulties in treating this co-infection are exacerbated by limits on antiretroviral drug (ARV) subsidies. In co-infected patients requiring HAART, lamivudine is the only covered drug active against HBV. Improving the prognosis and quality of care in these patients depends on finding solutions to these problems and applying the recommendations for the management of HIV/HBV co-infection.     

Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis.

BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.     

Hepatitis B screening practices and viral control among persons living with HIV in urban Senegal

Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg-positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co-infection among individual HBsAg tested. We determined the proportion of co-infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg-positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co-infection had a detectable HBV VL, of whom five were HIV-suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co-infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF-containing regimen.     

Hepatitis C virus infection: co-infection with HIV and HBV.

Hepatitis C shares common routes of infection with hepatitis B (HBV) and the human immunodeficiency virus (HIV). It is, therefore, not surprising to find that some patients with HCV are co-infected with either HIV and/or HBV. Until recently, the effects of HIV on HCV infection have not been investigated--sadly patients with HIV died long before their liver disease became problematic. However, the development of successful therapies for HIV have led to dramatic improvements in life expectancy for patients infected with this virus and in these patients, with well controlled HIV, it is becoming clear that hepatitis C may lead to the early onset of advanced liver disease. The optimal treatment for these patients is unknown but it seems likely that combination antiviral therapy will be required. The effects of HBV on HCV are also beginning to be investigated and, again, it is clear that co-infection leads to more aggressive liver disease with the two viruses interacting in poorly defined ways to increase the rate of hepatic fibrosis. Management of combined HCV/HBV infection is still under investigation and will probably involve combination therapy.     

Correlates of poor perceived health among individuals living with HIV and HBV chronic infections: a longitudinal assessment

Chronic hepatitis B virus (HBV) infection affects up to 14% of people living with HIV and AIDS (PLWHA) and is associated with a higher risk of non-AIDS death. While great advances have been made in the therapeutic management of co-infection with HIV and HBV, nothing is known about perceived health in people living with HIV and HBV. This study aimed at characterizing individuals with poor perceived overall health among 308 HIV-HBV co-infected individuals enrolled between May 2002 and May 2003 in a three-year French cohort. A binary score for perceived overall health (good vs. poor) was calculated from individuals' responses to the COOP-WONCA charts at cohort enrolment and at quarterly visits throughout the follow-up. Mixed models were used to explore factors associated with this score. At enrolment, 190 individuals (62%) reported poor overall health. In the multivariate analysis, low CD4 percentage, co-infection with hepatitis C or D viruses, HIV diagnosis before 1996 and HBeAg positivity were independently associated with poor perceived overall health. Poor perceived health concerns a considerable portion of individuals living with HIV and HBV. Individuals with wild-type HBV and multiple hepatitis infection require better clinical management. Further research is needed for hepatitis D virus infection, for which treatment options are currently very limited.     

Significance of blood analysis in hemophiliacs co-infected with human immunodeficiency virus and hepatitis viruses

AIM： To study the effect of hepatitis virus infection on cirrhosis and liver function markers in HIV-infected hemophiliacs.
METHODS： We have analyzed the immunological, liver function and cirrhosis markers in a cohort of hemophiliacs co-infected with human immunodeficiency virus （HIV） and hepatitis viruses.
RESULTS： There was no difference in immunological markers among co-infected patients and patients infected with HIV only and those co-infected with one or more hepatitis virus. Although liver function and cirrhosis markers remained within a normal range, there was a worsening trend in all patients co-infected with hepatitis virus C （HCV）, which was further exacerbated in the presence of additional infection with hepatitis virus B （HBV）.
CONCLUSION： Co-infection with HIV, HBV and HCV leads to worsening of hyaluronic acid and liver function markers. Increases in serum hyaluronic acid may be suggestive of a predisposition to liver diseases.     

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.     

Hepatitis B and C virus infections in the immune compromised

PURPOSE OF REVIEW: This review compares and contrasts the natural history and treatment of hepatitis B and C virus infections in three principal populations of immune compromised individuals: (1) patients co-infected with HIV; (2) patients with liver failure secondary to hepatitis B or C virus infection who undergo liver transplantation, and (3) patients with hepatitis B or C virus infection who undergo anticancer chemotherapy. RECENT FINDINGS: Chronic liver disease resulting from hepatitis B or C virus infection progresses more rapidly in patients co-infected with HIV than in HIV negative patients. Treatment protocols for antiviral therapy are, however, similar to those used in immunocompetent individuals and although few long-term results are available, the efficacy of interferon and ribavirin therapy in hepatitis C virus/HIV infection and lamivudine in HIV/hepatitis B virus infection has been proven in the short-term. Perhaps the most important consideration is the timing of administering treatments to co-infected patients. For patients with well preserved CD4 counts and hepatitis C virus/HIV co-infection, the hepatitis infection should be treated as early as possible to avoid drug interactions of hepatitis C virus antivirals with antiretroviral therapy. Also, response to hepatitis C virus treatment appears better when treatment is administered in the context of preserved immune function. Conversely, in hepatitis B virus/HIV co-infection, hepatitis B virus antivirals are best administered with anti-retroviral therapy, thus preventing the selection of HIV viral species which may be resistant to the drugs used for hepatitis B virus. Improved graft and patient survival after liver transplant and with anticancer chemotherapy in hepatitis B virus infected patients has been proven using lamivudine prophylaxis. However, although therapy for hepatitis C virus recurrence after liver transplantation would seem rational, limited success with current treatment protocols has been achieved. SUMMARY: Although the prognosis of hepatitis B and C virus infections in the immune compromised may be inferior to that of immunocompetent individuals, such patients should have full evaluation of their viral hepatitis, and antiviral therapy should be considered.     

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.     

Impact of hepatitis B virus co-infection on response to highly active antiretroviral treatment and outcome in HIV-infected individuals: a nationwide cohort study

BACKGROUND: The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. METHODS: This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. RESULTS: HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1-2.1], liver-related mortality (MRR 4.0; 95% CI 1.6-9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0-3.0). The presence of HBeAg did not influence patients' response to HAART. CONCLUSIONS: In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.     

13例HIV/HBV重叠感染患者的实验指标分析

目的了解艾滋病病毒与乙型肝炎病毒（HIV/HBV）重叠感染患者的临床特征,分析HIV与HBV在疾病进展中的相互作用。方法回顾性分析、比较13例HIV/HBV重叠感染组、28例单纯HIV感染组、28例单纯HBV感染组患者,在免疫功能、肝脏功能及血常规方面的差异。结果免疫功能检测：CD4^＋T细胞计数和CD4^＋/CD8^＋T细胞比值表现为HIV/HBV重叠感染组〈单纯HIV组〈单纯HBV组（P〈0.01）;肝脏功能检测：HIV/HBV重叠感染组与单纯HIV感染组各项指标无显著性差异,而单纯HBV组的丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素显著高于（P〈0.01）或高于（P〈0.05）另外两组;血常规检测：HIV/HBV重叠感染组和单纯HIV组各指标无显著性差异,但与单纯HBV组比较,则红细胞和血红蛋白显著降低（P〈0.01）,血小板明显升高（P〈0.01）。结论研究结果初步提示,HIV与HBV重叠感染后,可能减轻患者的肝细胞损伤,进一步降低患者的免疫功能。     

河北省HIV-1感染者中HCV和HBV合并感染状况调查

目的了解河北省艾滋病病毒Ⅰ型(HIV-1)感染者中,丙型肝炎病毒(HCV)、乙型肝炎(乙肝)病毒(HBV)的感染状况。方法采集了HIV-1感染者的抗凝全血样品,进行了HCV抗体和乙肝病毒表面抗原(HBsAg)的检测。结果 147例HIV-1感染者中,HCV感染率为17.7%(26/147),HBV感染率为15.0%(22/147),HCV/HBV混合感染率为3.4%(5/147)。在HIV-1感染者中,HCV的感染率在注射吸毒感染者中为100%(6/6),血液途径感染者中为73.3%(11/15),性感染者中为6.3%(7/111),不同感染途径间的差异有统计学意义(P<0.001);女性高于男性(P=0.002);低文化程度的感染者中感染率较高,文化程度方面差异有统计学意义(P<0.01)。在HIV-1感染者中,HBV的感染率小年龄组较高(P<0.05)。结论在HIV感染人群中,有较高的HCV和HBV感染率。     

北京地区人类免疫缺陷病毒感染者合并乙型肝炎病毒感染的流行病学特征及影响因素分析

目的分析北京市人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者合并乙型肝炎病毒(HBV)感染的流行病学特征,并探索影响合并感染的相关因素。方法对北京地区HIV/AIDS定点治疗医院(北京协和医院、北京地坛医院、北京佑安医院)长期随访的接受抗反转录病毒治疗(ART)的13253例HIV感染者临床资料进行回顾性分析。结果排除未进行HBV标志物检测的患者1681例,共有11572例HIV感染者纳入研究,其中HIV合并HBV感染的患者532例(4.6%),主要为青壮年(28~48岁)男性,占85.9%,感染途径以同性性传播为主(74.8%)。87.4%的合并感染患者基线治疗接受了包含拉米夫定(3TC)、替诺福韦(TDF)两种抗HBV药物的治疗。2013—2018年,HIV合并HBV感染的年新增感染率呈波动性下降的趋势,年均增长率分别为6.37%、4.55%、3.92%、4.68%、4.24%和2.74%。HIV合并HBV感染的主要影响因素为年龄(28~48岁比<28岁,OR=2.807,95%CI 1.241~6.345)以及婚姻状况(已婚比未婚,OR=1.259,95%CI 1.004~1.579)。结论北京地区HIV合并HBV感染率为4.6%;2013—2018年HIV合并HBV的年新增合并感染率呈下降趋势。青壮年(28~48岁)已婚HIV感染者合并HBV感染的风险较高。     

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.     

Genomic variability associated with the presence of occult hepatitis B virus in HIV co‐infected individuals

Summary. Occult hepatitis B virus (O‐HBV) infection is characterized by the presence of HBV DNA without detectable hepatitis B surface antigen (HBV DNA+/HBsAg?) in the serum. Although O‐HBV is more prevalent during HBV/HIV co‐infection, analysis of HBV mutations in co‐infected patients is limited. In this preliminary study, HBV PreSurface (PreS) and surface (S) regions were amplified from 33 HIV‐positive patient serum samples – 27 chronic HBV (C‐HBV) and six O‐HBV infections. HBV genotype was determined by phylogenetic analysis, while quasispecies diversity was quantified for the PreS, S and overlapping polymerase regions. C‐HBV infections harboured genotypes A, D and G, compared to A, E, G and one mixed A/G infection for O‐HBV. Interestingly, nonsynonymous–synonymous mutation values indicated positive immune selection in three regions for O‐HBV vs one for C‐HBV. Sequence analysis further identified new O‐HBV mutations, in addition to several previously reported mutations within the HBsAg antigenic determinant. Several of these O‐HBV mutations likely contribute to the lack of detectable HBsAg in O‐HBV infection by interfering with detection in serologic assays, altering antigen secretion and/or decreasing replicative fitness.