Anti-hepatitis C virus treatment may prevent the progression of liver fibrosis in non-responder human immunodeficiency virus/hepatitis C virus coinfected patients

AimTo evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon + Ribavirine regimen.Materials and methodsWe investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon + Ribavirine treatment (Group hepatitis C virus Rx) administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated) after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula.ResultsLiver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16%) patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups.ConclusionLiver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy.     

Management of hepatitis C in human immunodeficiency virus-infected patients

Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.     

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

Summary. In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57=75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation

Background/Aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation.Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC^TM assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection.Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p = 0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3–63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection.Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.     

Hyaluronic acid, transforming growth factor-β1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection

Summary.  Chronic hepatitis C virus (HCV) infection follows an accelerated course in patients co-infected with human immunodeficiency virus (HIV); establishing the extent of liver fibrosis is crucial for disease staging and determining treatment strategy in these patients. The utility of noninvasive markers of fibrosis as alternatives to liver biopsy has not been well-studied in these patients. We evaluated the predictive value of serum transforming growth factor-beta1 (TGF-β1) and hyaluronic acid (HA) levels for determining the extent of liver fibrosis. Liver biopsies and blood samples were collected from 69 consecutive patients (74% male; median age, 41 years) between May 2005 and November 2006. Serum TGF-β1 and HA were analysed using commercial kits. Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase levels were elevated in 81%, 70% and 60% of patients, respectively. Fifty-three patients (90%) were on highly active antiretroviral therapy and the median CD4-positive cell count was 422 cells/μL. The extent of fibrosis according to Scheuer's scoring was 32% F0 (no fibrosis), 16.5% F1, 16.5% F2, 26% F3 and 7% F4 (cirrhosis). Mean serum TGF-β1 was 36.1 ± 14.4 ng/mL; mean serum HA was 75.2 ± 85.0 μg/L. Serum HA was positively associated and significantly correlated with the stage of fibrosis ( r  =   0.56; P  <   0.05). The area under the curve for discriminating mild (F0–F2) from significant (F3–F4) fibrosis in receiver operating analysis using HA was 0.83 (sensitivity, 87%; specificity, 70%). These data suggest that HA is clinically useful for predicting liver fibrosis and cirrhosis in patients co-infected with HCV/HIV. However, serum TGF-β1 was not predictive of histological damage in co-infected individuals treated with HAART.     

Usefulness of elastometry in evaluating the extents of liver fibrosis in hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus.

The newly developed elastometer, FibroScan((R)), was utilized to evaluate liver fibrosis in hepatitis C virus (HCV)- and human immunodeficiency virus (HIV)-coinfected 33 hemophiliacs and HIV-uninfected 24 patients with chronic hepatitis C. Chronicity in the liver was categorized into 4 stages by abdominal ultrasound (AUS): 1 (normal or fatty liver); 2 (chronic liver disease, mild); 3 (moderate); and 4 (severe). Stiffness of the liver was significantly increased as AUS stages advanced: 5.4+/-2.2 (N=3) versus 7.5+/-2.7 (N=9), in stage 1; 4.9+/-1.7 (N=2) versus 9.9+/-6.0 (N=10), in stage 2, 13.5+/-4.7 (N=5) versus 12.9+/-5.9 (N=6), in stage 3, and 22.0+/-9.5 (N=14) versus 28.1+/-21.3 (N=8), in stage 4, in non-HIV group and in HIV group, respectively (P=0.004 and 0.007). Stiffness was correlated with AUS stages (r=0.740, P<0.001), platelet counts (PLT; r=-0.642, P=0.001) and 7S domain of type IV collagen (IV-coll; r=0.480, P=0.024) in non-HIV group, while in HIV group, with IV-coll (r=0.801, P<0.001), AUS stages (r=-0.603, P<0.001), procollagen type III peptides (P-III-P; r=0.621, P=0.001), PLT (r=-0.480, P=0.005), and hyaluronic acid (r=0.433, P=0.027). FibroScan((R)) is absolutely noninvasive and can be the alternative to liver biopsy, especially in patients with bleeding tendency.     

山东省HIV与HCV共感染者的流行病学分析

目的了解丙型肝炎病毒（HCV）在山东省艾滋病病毒（HIV）感染者中的感染状况,分析HIV、HCV共感染者的流行病学特征。方法对2000-2010年底,山东省报告的HIV感染者/艾滋病（AIDS）病人确证时的血样进行HCV检测,选取现在存活的、年龄≥18岁的HIV感染者和AIDS病人为研究对象,通过研究对象HIV确证后的首次随访调查表,收集流行病学信息,进行单因素分析和多因素Logistic回归分析。结果 HIV与HCV共感染率为41.7%（842/2 021）。单因素分析发现,不同文化程度、不同性别、籍贯和传染途径、不同民族之间差异有统计学意义（P〈0.05）,在此基础上进行多因素的Logistic回归分析发现,性别、籍贯和感染途径是HIV/HCV共感染的独立危险因子。结论不同性别、籍贯和传染途径中HIV、HCV共感染率不同,应引起重视。     

The effect of hepatitis C treatment and human immunodeficiency virus (HIV) co-infection on the disease burden of hepatitis C among injecting drug users in Amsterdam

Aims The hepatitis C virus (HCV) disease burden among injecting drug users (IDUs) is determined by HCV incidence, the long latency period of HCV, competing mortality causes, presence of co‐infection and HCV treatment uptake. We examined the effect of these factors and estimated the HCV disease burden in Amsterdam. Design A Markov model was developed, incorporating HCV and human immunodeficiency virus (HIV), and parameterized with data from the Amsterdam Cohort Studies, surveillance studies and literature. Setting IDU population of Amsterdam. Measurements HCV infection simulated from its acute phase to HCV‐related liver disease (i.e. decompensated cirrhosis and hepatocellular carcinoma). Findings The HCV prevalence among IDUs in Amsterdam increased to approximately 80% in the 1980s. From 2011 to 2025, the HCV‐related disease prevalence will accordingly rise by 36%, from 57 cases (95% range 33–94) to 78 (95% range 43–138), respectively. In total, 945 (95% range 617–1309) individuals will develop HCV‐related liver disease. This burden would have been 33% higher in the absence of HIV, resulting in 1219 cases (95% range 796–1663). In Amsterdam, 25% of HIV‐negative IDUs receive successful HCV treatment, reducing the cumulative disease burden by 14% to 810 (95% range 520–1120). Further reduction of 36% can be achieved by improving treatment, resulting in 603 cases (95% range 384–851). Conclusions The hepatitis C virus burden among injecting drug users in Amsterdam has been reduced by a high competing mortality rate, particularly caused by HIV infection, and to a smaller extent by hepatitis C virus treatment. Improved hepatitis C virus treatment is expected to contribute to reduce the future hepatitis C virus disease burden.     

Noninvasive diagnosis of liver fibrosis in patients with HIV infection and HCV/HBV co-infection

Summary.  The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.     

Treatment of hepatitis C virus and human immunodeficiency virus coinfection: from large trials to real life

To analyse the barriers for anti-hepatitis C virus (anti-HCV) treatment in human immunodeficiency virus (HIV)-HCV coinfected patients, we surveyed 71 physicians specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS information and care (17%), haematology (10%) and hepatology (6%). A standard data collection form was used to identify patients observed in 7 days in November 2004. Three hundred and eighty patients with the following characteristics were included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago; routes of transmission via injection drug use (78%); undetectable HIV viral load (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of 369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been carried out in 56%. There were several explanations for the nontreatment of HCV in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti-HCV treatment was deemed questionable (n = 109) because of minor hepatic lesions, alcohol consumption, or active drug use; no liver biopsy had been performed (n = 68); treatment was contraindicated (n = 62), mainly for psychiatric reasons; there was physician conviction of poor patient compliance (n = 62) and patient refusal (n = 33). Patients having received anti-HCV treatment (n = 91) compared with those who had never received any (n = 205) were more commonly of European origin, had better control of their HIV infection, were followed by a hepatologist more often, had a liver biopsy more often and had more commonly a high HCV viral load (P < 0.001). In 'real life' in France in 2004, more than half of the HIV-HCV coinfected patients have never received anti-HCV treatment. The main reasons are a treatment that may be deemed questionable (minimal hepatic lesions, alcohol, active drug use), a lack of available liver biopsy, a psychiatric contraindication and physician conviction of poor patient compliance.     

人类免疫缺陷病毒感染者混合感染丙型和乙型肝炎病毒后对高效抗逆转录病毒治疗疗效的影响

目的 观察HIV感染者合并HCV和HBV感染后对高效抗逆转录病毒治疗(HAART)疗效的影响.方法 对某地区HIV、HCV共感染患者166例(HIV+HCV组),HIV、HCV和HBV混合感染患者23例(H1V+HCV+HBV组)及单纯HIV感染者178例,给予1年的HAART治疗,观察3组患者病毒学反应、免疫学反应和肝功能动态变化.以流式细胞仪检测外周血CD4+T淋巴细胞;实时PCR定量检测HCV、HIV和HBV病毒载量.结果 单纯HIV感染组、HIV+HCV+HBV组和HIV+HCV组经HAART 1年后,HIV病毒载量分别由治疗前(6.78±1.08)、(6.23±1.34)、(6.54±1.23)lg拷贝/ml下降至(0.53±0.15)、(0.67±0.16)、(0.43±0.11)lg拷贝/ml(P值均＜0.001).CD4+T淋巴细胞计数分别由治疗前的(197±127)、(184±113)、(213±143)个/μl上升至(382±74)、(383±70)、(378±76)个/μl(P值均＜0.001).3组之间各时间点CD4+T淋巴细胞、HIV病毒载量差异无统计学意义.3组患者ALT、AST、总胆红素治疗前后无显著变化,相同时间点组间比较差异无统计学意义.HAART前后,HCV病毒载量差异无统计学意义.结论 HIV感染者混合感染HBV和(或)HCV,不影响HAART的疗效;HAART对HCV复制无抑制作用.     

Patients co-infected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA

Serum and liver hepatitis C virus (HCV) RNA levels in patients with hepatitis C have previously been quantified using different techniques. In this work, we used an automated, multicycle, polymerase chain reaction (PCR)-based technique to quantify HCV RNA in 1-2 mm of frozen liver tissue, and in serum, from 70 patients with antibodies to HCV (anti-HCV), with and without human immunodeficiency virus (HIV) co-infection. Stored liver tissue and sera collected at the time of liver biopsy were used for measurement of HCV RNA. Forty-eight HCV patients and 22 HIV/HCV co-infected patients were studied. Co-infected patients had significantly higher median serum and liver HCV RNA (6.7 log copies ml-1 serum and 2.90 log copies microg-1 liver nucleic acids) than patients with HCV alone (6.2 log copies ml-1 serum and 2.19 log copies microg-1 liver nucleic acids). There was only a weak correlation between serum and liver HCV RNA (r = 0.43). There was no correlation between liver and serum HCV RNA and host factors such as duration of disease, CD4 counts, alanine aminotransferase levels or histological score. There was no correlation with HCV genotype. Co-infected patients were more likely to harbour HCV genotype 1 (85%) when compared to patients with HCV alone (58%). An identical genotype was found in liver and serum in 89% of those tested; in 11%, a mixed genotype was present in serum. Patients with HCV genotypes 1 and non-1 had similar histological scores. Hence, an automated PCR-based technique is useful for measuring both liver and serum HCV RNA. Serum HCV genotypes closely paralleled those found in liver tissue. HIV co-infection was associated with higher serum, as well as intrahepatic, HCV RNA levels, by mechanisms not directly related to CD4 counts. The lack of correlation between liver HCV RNA and histology suggests that HCV is not directly cytopathic.     

含克力芝组合的HAART方案对HIV/HCV混合感染的疗效探讨

目的探讨含克力芝(LPV/r)组合的高效抗反转录病毒治疗(HAART)方案,对艾滋病病毒(HIV)、丙型肝炎病毒(HCV)混合感染治疗的效果。方法采用前瞻性研究方法,选择HIV/HCV混合感染患者43例,通过Spw-Pb网络数据平台随机分为研究组与对照组。研究组22例,采用以洛匹那韦/利托那韦(LPV/r)为基础的HAART治疗方案;对照组21例,采用以依非韦伦(EFV)为基础的HAART治疗方案。研究组与对照组检测基线CD4+T淋巴细胞计数、HIV病毒载量、丙氨酸转氨酶(ALT)、胆固醇(CHO)、甘油三酯(TG)等指标;治疗后48周分别检测上述指标,研究终点为48周。观察病毒学、免疫学、ALT、CHO、TG等指标的变化。结果 HAART治疗48周,研究组与对照组HIV-RNA阴转率比较差异无统计学意义(P>0.05)。研究组与对照组基线CD4+T淋巴细胞、ALT、CHO、TG比较差异无统计学意义(均P>0.05);HAART治疗48周,研究组CD4+T淋巴细胞计数增长明显高于对照组,差异有统计学意义(P<0.05);而研究组与对照组ALT、CHO、TG比较差异无统计学意义(均P>0.05)。结论含LPV/r组合的抗病毒方案对HIV/HCV混合感染治疗效果较优越,CD4+T淋巴细胞增长较明显,胆固醇、甘油三酯变化不大,建议HIV/HCV混合感染HAART治疗选择LPV/r方案为佳。     

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.     

Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus

Summary. We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV‐coinfected patients. We studied all consecutive HIV/HCV‐coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut‐off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV‐coinfected patients.