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.     

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV)

Abstract: We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.     

Human immunodeficiency virus-hepatitis C coinfection: swapping new problems for newer ones

Abstract Recent successes in HIV therapy have uncovered other health problems for HIV-infected individuals. Hepatitis C has become an especially significant problem, partly due to its faster progression in an immunocompromised setting. In addition, the higher viral loads in coinfected patients likely result in more efficient perinatal and perhaps even sexual transmission. Therapy has largely been neglected, despite data suggesting its efficacy in HIV–HCV coinfected patients. Studies of combination interferon and ribavirin studies are lacking, although underway. A major concern is the potential inactivation of certain thymidine analogues by ribavirin. Some antiretroviral therapies, such as ritonavir, indinavir and nevirapine, may enhance liver toxicity in coinfected patients and should be avoided if possible. The role of chronic low-grade liver function abnormalities remains uncertain and requires further investigation. (Intern Med J 2001; 31: 418–421)     

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.     

Inhibition of marrow CFU-E colony formation from human immunodeficiency virus-infected patients by β- and γ-interferon

Increased production of cytokines such as β-interferon (IFN) and γ-IFN may contribute to the anemia frequently observed in patients with human immunodeficiency virus (HIV) infection. The hypothesis that HIV infection might enhance the susceptibility of erythroid progenitors to cytokine-mediated inhibition was evaluated by comparing the effects of β- and γ-IFN on in vitro colony formation by marrow erythroid colony-forming units (CFU-E) from HIV patients, normal volunteers, and anemic non-HIV-infected individuals. CFU-E colony formation from HIV patients was not significantly different from controls, and the degree of inhibition by IFN did not differ among patient subsets. HIV infection does not appear to impair baseline CFU-E colony formation, nor does it appear to enhance the susceptibility of CFU-E to suppression by cytokines. © 1996 Wiley-Liss, Inc.     

Usefulness of combined measurement of serum bile acids and ferritin as additional prognostic markers to predict failure to reach sustained response to antiviral treatment in chronic hepatitis C

AIM: To investigate the relationship between serum levels of ferritin and bile acids (BA) and the response to antiviral treatment in chronic hepatitis C (HCV). METHODS: A retrospective study was carried out on 35 control volunteers and 50 patients receiving interferon alpha-2b alone or plus ribavirin for 48 weeks. These were classified as sustained responders (SR) for >6 months after therapy (n = 17), non-responders (NR) (n = 27) and relapsers (RL) (n = 6). Before treatment, serum ferritin levels were determined by immunoturbidometry, 3alpha-hydroxyl-BA levels (S-3alpha-OH-BA) were assayed enzymatically and total (desulfated, deglucuronidated and deamidated) BA concentrations (STBA) by gas chromatography-mass spectrometry. RESULTS: STBA were lower in controls than in patients (SR < NR + RL). The highest levels of cholic acid and chenodeoxycholic acid families were found in NR + RL. Levels of cholic acid family were similar in controls and SR, whereas those of chenodeoxycholic acid family were higher in SR than in controls. A significant correlation between STBA (but not S-3alpha-OH-BA) and ferritin was found. Apparent value to predict the absence of a sustained response was calculated by combining elevated ferritin (>300 microg/mL) and STBA or individual BA species at different cut-off values. The best degree of certainty (100% specificity) was obtained using STBA >15 microM. CONCLUSION: These results recommend that larger prospective trials should be performed in chronic HCV patients to evaluate the usefulness of combined measuring of STBA and ferritin as additional prognostic markers to predict the existence of a very low probability of a sustained response to the current standard treatment, i.e. pegylated interferon in combination with ribavirin.     

Documented rapid course of hepatic fibrosis between two biopsies in patients coinfected by HIV and HCV despite high CD4 cell count

In HIV/hepatitis C virus (HCV)-coinfected patients, it is recommended to repeat liver biopsy every 3 years when anti-HCV treatment is not indicated. We studied fibrosis progression in HIV/HCV-coinfected patients, who were not receiving anti-HCV treatment, on the basis of two successive liver biopsies. Thirty-two patients were retrospectively included. Twenty-six patients (79%) were on antiretroviral treatment at the first biopsy. The mean CD4 cell count was 470 +/- 283/mm(3). Three patients were staged F2 and the remainder F0/F1. The median interval between the two biopsies was 49 (24-80) months. At the second biopsy, the stage distribution was F0 0%, F1 41% (n = 13), F2 34% (n = 11), F3 19% (n = 6) and F4 6% (n = 2). The mean fibrosis progression rate (FPR) was 0.25 points/year. Nine patients (28%) were considered as rapid fibrosis progressors (progression by more than two points) and their FPR was 0.5 point/year; comparison of these subjects with the other 23 patients showed no relation between FPR and age, alcohol consumption, CD4+ cell count, HIV viral load, HCV genotype, aspartate aminotransferase or alanine aminotransferase. Analysis of the treatment received between the two liver biopsies did not find any correlation between liver FPR and a specific compound. Fifteen patients started anti-HCV therapy based on the second biopsy. Liver fibrosis in HIV/HCV-coinfected patients should be evaluated at least every 3 years, as nine of 32 (28%) of our patients progressed by at least two fibrosis points despite a high CD4+ cell count. The second biopsy showed that 15 patients (45%) qualified for anti-HCV therapy. Development of noninvasive methods of fibrosis evaluation should permit more frequent monitoring.     

Case report of acute-on-chronic liver failure secondary to diffuse large B-cell lymphoma

Acute liver failure is a rare presentation of hematologic malignancy. Acute on chronic liver failure(ACLF) is a newly recognized clinical entity that describes acute hepatic decompensation in persons with preexisting liver disease. Diffuse large B-cell lymphoma(DLBCL) is an aggressive non-Hodgkin’s lymphoma(NHL) with increasing incidence in older males, females and blacks. However, it has not yet been reported, to present with acute liver failure in patients with preexisting chronic liver disease due to human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infection. We describe a case of ACLF as the presenting manifestation of DLBCL in an elderly black man with HIV/HCV coinfection and prior Hodgkin’s disease in remission for three years. The rapidly fatal outcome of this disease is highlighted as is the distinction of ACLF from decompensated cirrhosis. Due to the increased prevalence of HIV/HCV co-infection in the African American 1945 to 1965 birth cohort and the fact that both are risk factors for chronic liver disease and NHL we postulate that the incidence of NHL presenting as ACLF may increase.     

HCV/ HIV co‐infection: time to re‐evaluate the role of HIV in the liver?

Summary.  Because of major advances in the treatment of HIV/AIDS, HIV-positive persons now live longer, healthier lives; however, hepatitis C virus (HCV) is increasingly recognized as a major cause of morbidity and mortality in this population. Among HCV-infected persons, HIV co-infection is associated with increased HCV RNA levels, increased hepatic inflammation and fibrosis, and more rapid progression to cirrhosis and end-stage liver disease. Compounding this problem are reduced HCV treatment response rates among HCV/HIV co-infected persons. Moreover, antiretroviral therapy used to suppress HIV replication is often associated with a paradoxical increase in HCV RNA levels, as well as hepatotoxicity. Despite the adverse clinical consequences of HCV/HIV co-infection, the mechanisms by which these two viruses interact at the cellular level remain largely unexplored. This review focuses on the evidence demonstrating direct infection of hepatocytes by HIV, as well as the indirect mechanisms by which HIV may regulate HCV replication at the cellular level. A comprehensive understanding of virus–virus and virus–cell interactions is critical to the development of novel treatment strategies to combat HCV/HIV co-infection.     

Chronic hepatitis C in patients co-infected with human immunodeficiency virus in Japan: a retrospective multicenter analysis

Aim:  A nationwide survey in Japan revealed that nearly one-fifth of human immunodeficiency virus (HIV)-positive patients are co-infected with hepatitis C virus (HCV). We conducted a study to further analyze the features of liver disease in HIV–HCV co-infected patients.
Methods:  We analyzed 297 patients from eight hospitals belonging to the HIV/AIDS Network of Japan.
Results:  HCV genotypes 1, 2, 3, 4 and mixed genotypes were detected in 55.2, 13.7, 18.9, 0.9 and 11.3% of patients, respectively, in contrast to the fact that only genotypes 1 and 2 are detected in HCV mono-infected patients in Japan. This is compatible with the transmission of HCV through imported blood products contaminated by HCV. Sixteen of 297 HIV–HCV co-infected patients had advanced liver disease accompanied by ascites, hepatic encephalopathy or hepatocellular carcinoma. The average age of such patients was 41.1 ± 14.0 years, which was much younger than that of HCV mono-infected patients with the same complications. The progression speed of liver disease estimated from the changes in the levels of serum albumin, bilirubin, or platelet was slower in patients who achieved sustained virological response with interferon treatment than in those who did not receive it. The overall sustained virological response rate to interferon treatment was 43.3%.
Conclusions:  Our findings suggest that liver disease is more advanced in HIV–HCV co-infected patients than in HCV mono-infected patients, and interferon treatment may retard the progression of liver disease in such patients.     

Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C

Changes in serum hyaluronic acid (HA) in 35 patients treated with interferon (IFN) were studied and the histological change in fibrosis was analysed. Serum HA levels and hepatitis C virus (HCV) RNA were followed from the start of therapy to 12 months after completion of treatment. Histological changes in pre- and post-treatment liver biopsies were assessed using a modified Knodell's scoring system. The serum levels of HA (r = 0.79; P<0.0001) correlated with the degree of fibrosis more closely than with that of amino terminal peptides of type III procollagen (PIIIP; r = 0.45; P<0.05) or type IV collagen (IV-C; r = 0.42; P<0.05). Only complete responders (CR) had a significant decrease in serum levels of HA and IV-C (P<0.05), in parallel with histological improvement (P<0.01). Neither partial responders (PR) nor non-responders (NR) had significant changes in histological scores and in serum levels of fibrotic markers. Significant differences were observed between CR and NR, both in HA levels (P<0.01) and PIIIP levels (P<0.05) 12 months after the cessation of treatment. These results suggest that serum HA is an indicator of the extent of fibrosis in chronic hepatitis C. Serial determinations of serum HA levels may be of use for monitoring the histological response of hepatic fibrosis to IFN treatment in chronic hepatitis C.     

Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance

BACKGROUND & AIMS: Acute hepatitis C virus infection accounts for approximately 20% of cases of acute hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for acute hepatitis C virus. METHODS: The diagnosis of acute hepatitis C virus in 60 patients was based on seroconversion to anti-hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of hepatitis C virus RNA in the first serum sample. RESULTS: Fifty-one of 60 (85%) patients presented with symptomatic acute hepatitis C virus. In the natural (untreated) course of acute symptomatic hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic hepatitis C. The start of antiviral therapy (interferon-alpha with or without ribavirin) beyond 3 months after the onset of acute hepatitis induced sustained viral clearance in 80% of treated patients. CONCLUSIONS: The management of acute hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic acute hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.     

Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients

BACKGROUND AND AIMS: Kinetic modeling of hepatitis C virus (HCV) response to interferon (IFN)-based therapy provides insights into factors associated with treatment outcomes. HCV/human immunodeficiency virus (HIV)-co-infected patients show lower response rates vs. HCV-monoinfected patients. Reasons for this remain unclear. This study evaluated kinetic parameters and treatment responses in co-infected vs monoinfected patients. METHODS: Co-infected patients were randomized within a US multicenter trial (ACTG 5071) to receive pegylated-interferon (PEG-IFN) alfa-2a + ribavirin vs. IFN alfa-2a + ribavirin. Monoinfected controls were matched prospectively for treatment, genotype, age, sex, race, and histology. Quantitative HCV-RNA testing was performed at hours 0, 6, 12, 24, 48, and 72; days 7, 10, 14, 28, and 56; and weeks 12, 24, 48, and 72. RESULTS: Twelve HCV/HIV-co-infected and 15 HCV-monoinfected patients underwent viral kinetic sampling. Among HIV-positive patients the mean CD4(+) count was 325 cells/mm(3). Seventy-five percent of patients were genotype 1. The HCV-RNA level was undetectable at 72 weeks in 25% and 40% of co-infected and monoinfected patients, respectively. Phase 1/2 declines, free virus clearance rate, and infected hepatocyte death rate were not affected by co-infection status but differed by treatment. Efficiency (epsilon) > or = 90% at 60 hours was associated with viral clearance ( P = .02). Modeling with pooled parameters suggests baseline viral load is a key factor in time to response in this cohort. Predicted clearance time increased by 28% in co-infected patients. CONCLUSIONS: Co-infection status did not affect key kinetic parameters. Among kinetic parameters, efficiency was associated significantly with viral clearance. Co-infected patients may require longer treatment duration than monoinfected patients given their generally higher baseline viral loads.     

Amantadine therapy for chronic hepatitis C

OBJECTIVE: Although treatment of hepatitis C has improved, up to 50% do not respond to standard therapy with interferon regimes or cannot tolerate the treatment due to side effects. The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferon. DESIGN: A prospective double-blind randomized placebo-controlled trial. SETTING: Outpatient research clinic of a teaching hospital. PATIENTS/PARTICIPANTS: One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes, detectable hepatitis C RNA in the blood, and abnormal liver histology by biopsy were randomized to receive treatment or placebo. MEASUREMENTS AND MAIN RESULTS: Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months. After 6 months, placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy. Amantadine therapy resulted in a significant decline in serum alanine aminotransferase compared to placebo (P =.03). Nine percent cleared the virus at the end of therapy and 6.8% had a sustained virologic response 6 months after discontinuation of amantadine, but this was not statistically significant. Side effects were minimal, and the social quality of life survey improved with 12 months of amantadine (P =.02). CONCLUSIONS: Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon.     

Analysis of Biochemical and Virological Efficacy of Human Lymphoblastoid Interferon (IFN) in Patients with Compensated Type C Liver Cirrhosis

A controlled trial was conducted to compare the efficacy of interferon (IFN) between two groups of patients with type C liver. Thirty-five patients were randomly assigned to group A (17 patients) or group B (18 patients). The former received 3 megaunits (MU) of human lymphoblastoid IFN six days per week for two weeks, followed by three days per week for 50 weeks; the latter group received 6 MU six days per week for two weeks followed by three days per week for 24 weeks. The percentages of biological sustained responders (B-SR) and virological sustained responders (V-SR) were 29.4 and 23.5%, respectively, in group B, and 17.6% for both in group A. The therapeutic effects were not different between two groups. HCV genotype 2 accounted for significantly higher percentage of B-SR and V-SR (both 57.1%, respectively). These findings indicate that IFN is effective in type C cirrhosis with genotype 2.     

Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral hepatitis

Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were investigated in a case-control study conducted in 107 human immunodeficiency virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22 hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P = 0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4 counts, being HBsAg-positive was strongly associated with having negative serum HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may favour the elimination of HCV in HIV-infected patients, which may influence liver disease and therapeutic decisions.     

Findings and benefit of liver biopsies in 46 patients infected with human immunodeficiency virus

AIMS: The aim of this work is to evaluate the role of liver biopsy and to determine the histological findings in patients infected with the human immunodeficiency virus (HIV) who have abnormal liver function tests (LFT). METHODS: We performed a percutaneous liver biopsy in 46 HIV-seropositive patients with abnormal LFT. Parts of biopsied tissue were used for bacterial and fungal culture and the rest was processed for histological examination including special staining. RESULTS: Of these 46 patients, 41 patients were males and five were females. The median age was 31+/-6 years. Mycobacterium tuberculosis was the most common histological finding (15 cases). Of 15 tuberculosis patients, 11 (73.3%) had lymphadenopathy and positive acid-fast bacilli (AFB) in node aspiration or biopsy. The other findings included AFB-negative granuloma (eight cases), histoplasmosis (six cases), cryptococcosis (six cases), penicillosis (four cases), viral hepatitis: hepatitis C virus (HCV; one case), hepatitis B virus and HCV infection (one case), fatty liver (two cases), drug-induced hepatitis (one case) and non-specific changes (five cases). There were double infections in three patients. We were able to demonstrate opportunistic infections in 41 cases (89.3%). CONCLUSIONS: Mycobacterium tuberculosis was the most common histological finding in HIV patients with abnormal LFT in Thailand. Liver biopsy was a useful procedure in evaluating abnormal LFT in HIV patients.