Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases
TL;DR: Early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV‐infection, according to a retrospective survey of HIV‐positive patients with acute HCV infection.
Abstract: Summary. Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.
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TL;DR: Eleven areas have been identified in which new recommendations are particu-larly needed: management of patients with persistently normalaminotransferasesliverrosis assessment: when and how predictors of response to anti-HCV therapy in coinfected patients, and interactions between HCV medications and antiretroviraldrugs.
Abstract: Chronic hepatitis C (HCV) infection is currently oneof the most clinically relevant comorbidities in theHIV population; overall, it affects one third of HIV-positive individuals [1]. Progression to end-stage liverdisease occurs faster in coinfected patients [2–4] anddecompensated cirrhosis is one of the main causes ofhospitalization and death in this population [5–8].However, the risk of hepatotoxicity using antiretroviraldrugs is increased in subjects with underlying HCVinfection [9,10]. Therefore, the optimal managementof chronic HCV in HIV-positive patients is currentlyapriority.Several guidelines for caring for HCV infection in HIV-positive individuals have been released [11–15]. Becausenew and relevant information has recently appeared, it isconvenient to update them. Eleven areas have beenidentified in which new recommendations are particu-larly needed:management of patients with persistently normalaminotransferasesliver fibrosis assessment: when and howpredictors of response to anti-HCV therapy in coinfectedpatientsoptimal dosages of pegylated interferon (pegIFN) andribavirin (RBV)optimal duration of anti-HCV therapytreatment of non-responders and/or relapserscare of patients with end-stage liver diseasetreatment of acute HCV infection in HIV-infectedindividualsmanagement of patients with multiple hepatitis virusesinteractions between HCV medications and antiretroviraldrugshepatotoxicity of antiretroviral drugs.
345 citations
Cites background from "Treatment of acute hepatitis C infe..."
...However, the rates of HCV clearance obtained in HIVpositive patients treated during the acute phase are much higher (up to 80%) [147,152] than in chronic HCV infection....
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TL;DR: An international phylogenetic study revealed a large international network of HCV transmission among HIV-positive MSM, supported by the large proportion of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size.
315 citations
TL;DR: The emergence of an MSM-specific transmission network suggests that HIV-positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV.
Abstract: We retrospectively screened 1836 men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (1984–2003) for hepatitis C virus (HCV) antibodies. HCV incidence was 0.18/100 person-years (PY) in human immunodeficiency virus (HIV)–positive MSM (8/4408 PY [95% confidence interval {CI}, 0.08–0.36]) but was 0/100 PY in MSM without HIV (0/7807 PY [95% CI, 0.00–0.05]). After 2000, HCV incidence among HIV-positive men increased 10-fold to 0.87/100 PY (5/572 PY [95% CI, 0.28–2.03]). Additional hospital cases ( ) showed that MSM in Amsterdam who acquired HCV infection after 2000 reported high rates of n p 34 ulcerative sexually transmitted infections (59%) and rough sexual techniques (56%), denied injection drug use, and were infected mainly with the difficult-to-treat HCV genotypes 1 (56%) and 4 (36%). Phylogenetic analysis showed 3 monophyletic clusters of MSM-specific HCV strains. The emergence of an MSM-specific transmission network suggests that HIV-positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV. Targeted prevention and routine HCV screening among HIV-positive MSM is needed to deter the spread of HCV.
298 citations
Cites background from "Treatment of acute hepatitis C infe..."
...genotypes 1 and 4 are conflicting but promising [11, 42, 44]....
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TL;DR: Testing for HCV RNA by PCR is the only reliable test for the diagnosis of acute infection and patients with jaundice have a higher likelihood of spontaneous viral clearance than do asymptomatic patients, and thus should be monitored for at least 12 weeks before initiating antiviral therapy.
257 citations
TL;DR: In this paper, the authors synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute hepatitis C virus among HIV-infected MSM.
Abstract: Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.
252 citations
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TL;DR: The classification system for HIV infection is revised to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions and the AIDS surveillance case definition is expanded.
Abstract: The following CDC staff members prepared this report: National Center for Infectious Diseases Division of HIV/AIDS Kenneth G. Castro, M.D. John W. Ward, M.D. Laurence Slutsker, M.D., M.P.H. James W. Buehler, M.D. Harold W. Jaffe, M.D. Ruth L. Berkelman, M.D. Office of the Director Associate Director for HIV/AIDS James W. Curran, M.D., M.P.H. 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults Summary CDC has revised the classification system for HIV infection to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions. This classification system replaces the system published by CDC in 1986 (1) and is primarily intended for use in public health practice. Consistent with the 1993 revised classification system, CDC has also expanded the AIDS surveillance case definition to include all HIV-infected persons who have less than 200 CD4+ T-lymphocytes/uL, or a CD4+ T-lymphocyte percentage of total lymphocytes of less than 14. This expansion includes the addition of three clinical conditions
4,203 citations
TL;DR: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferonalfa- 2a plus Ribavirin or pegin terferonAlfa-3a monotherapy.
Abstract: Background Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. Methods A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 μg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per millil...
1,194 citations
TL;DR: In this article, the authors assess the incidence and determinants of viral clearance and end-stage liver disease (ESLD) among persons who acquired hepatitis C virus infection from injection drug use.
Abstract: Context Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. Objective To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. Design and setting Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. Subjects A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. Main outcome measures Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. Results Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. Conclusions Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456
1,101 citations
TL;DR: Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes to indicate that the evolutionary dynamics of theHCV quasispecies during the emergency phase predict whether the infection will resolve or become chronic.
Abstract: The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies), whereas progressing hepatitis correlated with genetic evolution of HCV. Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion. These data indicate that the evolutionary dynamics of the HCV quasispecies during the acute phase of hepatitis C predict whether the infection will resolve or become chronic.
907 citations
TL;DR: Treatment of acute hepatitis C with interferon alfa-2b with treatment during the acute phase could prevent the development of chronic infection.
Abstract: Background In people who are infected with the hepatitis C virus (HCV), chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection. Methods Between 1998 and 2001, we identified 44 patients throughout Germany who had acute hepatitis C. Patients received 5 million U of interferon alfa-2b subcutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. Results The mean age of the 44 patients was 36 years; 25 were women. Nine became infected with HCV through intravenous drug use, 14 through a needle-stick injury, 7 through medical procedures, and 10 through sexual contact; the mode of infection could not be determined in 4. The average time from infection to the first signs or symptoms of hepatitis was 54 days, and the average time from infection until the start of therapy ...
782 citations