Liver steatosis in hepatitis C positive hemodialysis patients and factors affecting IFN-2a treatment

OBJECTIVE: Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD) patients. It is well known that HCV causes approximately 50% of hepatosteatosis in patients with normal renal function and that this rate is higher in patients infected with genotype 3. The aim of this study was to investigate the rate of steatosis, the regression in steatosis with interferon (IFN) treatment and factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C (CHC). MATERIAL AND METHODS: Thirty-seven HD patients with CHC were included in the study. All patients received hemodialysis treatment three times a week during the follow-up period. Patients were treated with 3 million units (MU) of IFN-alpha 2a monotherapy for at least 6 months. All patients were evaluated by liver biopsy before therapy and 16 were evaluated at 12-month follow-up. RESULTS: Mean age of the 37 patients (23 M, 14 F) was 44+/-11.6 years and body mass index was 21.8+/-1.8 kg/m2. Twenty-eight of the patients included in the study (75.7%) were of genotype 1b. RNA response after treatment was 78.4% and sustained response after the follow-up period of 14.9+/-8 months was 54%. Total cholesterol values were directly proportional to RNA response (p<0.003) and inversely correlated with resistance to treatment (p<0.008). Triglyceride values were inversely correlated with resistance to treatment (p<0.041). At evaluation of steatosis scores in baseline liver biopsy, severe and mild to moderate steatosis was found in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there was no steatosis. The rate of steatosis was found to be 44% in control biopsies. While there was no regression in the rates of steatosis (p=0.499), it was found that steatosis regressed after IFN treatment in two patients infected with genotype 3. No correlations were observed between HCV genotype, sustained response and liver steatosis. CONCLUSIONS: Response and sustained response rates of HD patients with HCV in a Turkish population were found to be high after IFN monotherapy. With the exception of two patients infected with genotype 3a, the rate of liver steatosis was found to be high and did not change after IFN treatment in HD patients with CHC.     

A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs

Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self-administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon-treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.     

Hepatitis C virus RNA detection in serum and peripheral blood mononuclear cells of patients with hepatitis C

ＨｅｐａｔｉｔｉｓＣｖｉｒｕｓＲＮＡｄｅｔｅｃｔｉｏｎｉｎｓｅｒｕｍａｎｄｐｅｒｉｐｈｅｒａｌｂｌｏｏｄｍｏｎｏｎｕｃｌｅａｒｃｅｌｓｏｆｐａｔｉｅｎｔｓｗｉｔｈｈｅｐａｔｉｔｉｓＣＺＨＯＵＰｉｎｇ，ＣＡＩＱｉｎｇ，ＣＨＥＮＹｏｕＣｈｕｎ，ＺＨＡ...     

Management of Hepatitis C in Patients with Chronic Kidney Disease

Chronic kidney disease represents a global health problem. Chronic hepatitis C virus (HCV) infection is prevalent in patients with end stage renal disease (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant impact on morbidity and mortality. Furthermore, HCV can cause various forms of glomerulopathy with the predominant type being cryglobulinemia associated membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as markers of liver injury; however, there is wide variation in aminotransferase levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC) in patients with ESRD is based on HCV antibody testing and further confirmation with polymerase chain reaction testing. Current standard therapy for CHC is composed of pegylated interferon and ribavirin. However, this combination is challenging in patients with ESRD due to its tolerability. We describe in this review relevant issues in epidemiology, diagnosis and management of CHC in ESRD, HD and renal transplant recipients.     

Hepatitis C and hepatitis B seroprevalence and associated risk factors in hemodialysis patients in Guilan province, north of Iran: HCV and HBV seroprevalence in hemodialysis patients

Background

Hepatitis C virus (HCV) and hepatitis B virus (HBV) infection are especially problematic in patients with end-stage renal disease who are undergoing hemodialysis (HD).

Objectives

To determine the prevalence of HCV and HBV infection in HD population in Guilan, north of Iran.

Patients and Methods

In a cross-sectional study, from May to September 2009, in 11 different hemodialysis units in Guilan province, North of Iran, clinical data such as age, gender, duration of dialysis, HBsAg and anti-HCV antibody of 514 HD patients were recorded. Patients with positive antibodies against HCV were tested for HCV RNA.

Results

From 514 patients, 286 (55.64%) were male. 61 (11.9%) patients were anti-HCV-positive and 31 (50.8%) were HCV PCR-positive. There was significant relationship between HCV Ab-positivity with gender and HD duration (p < 0.05). There was significant difference between the mean HD duration in anti-HCV-positive and anti-HCV-negative patients (p < 0.05). Also, significant relationship was found between HCV RNA-positivity with gender and HD duration (p < 0.05). Seven (1.4%) patients were positive for HBsAg. Two (0.38 %) were found positive for both HBsAg and anti-HCV antibody.

Conclusions

There is low a prevalence of HCV and HBV in HD patients in our region. The rate can be decreased by HBV vaccination of end-stage renal disease patients before setting chronic HD, antiviral treatment and isolation of infected individuals.     

Liver steatosis in hepatitis C positive hemodialysis patients and factors affecting IFN-2a treatment

Objective. Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD) patients. It is well known that HCV causes approximately 50% of hepatosteatosis in patients with normal renal function and that this rate is higher in patients infected with genotype 3. The aim of this study was to investigate the rate of steatosis, the regression in steatosis with interferon (IFN) treatment and factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C (CHC). Material and methods. Thirty-seven HD patients with CHC were included in the study. All patients received hemodialysis treatment three times a week during the follow-up period. Patients were treated with 3 million units (MU) of IFN-α 2a monotherapy for at least 6 months. All patients were evaluated by liver biopsy before therapy and 16 were evaluated at 12-month follow-up. Results. Mean age of the 37 patients (23 M, 14 F) was 44±11.6 years and body mass index was 21.8±1.8 kg/m². Twenty-eight of the patients included in the study (75.7%) were of genotype 1b. RNA response after treatment was 78.4% and sustained response after the follow-up period of 14.9±8 months was 54%. Total cholesterol values were directly proportional to RNA response (p<0.003) and inversely correlated with resistance to treatment (p<0.008). Triglyceride values were inversely correlated with resistance to treatment (p<0.041). At evaluation of steatosis scores in baseline liver biopsy, severe and mild to moderate steatosis was found in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there was no steatosis. The rate of steatosis was found to be 44% in control biopsies. While there was no regression in the rates of steatosis (p=0.499), it was found that steatosis regressed after IFN treatment in two patients infected with genotype 3. No correlations were observed between HCV genotype, sustained response and liver steatosis. Conclusions. Response and sustained response rates of HD patients with HCV in a Turkish population were found to be high after IFN monotherapy. With the exception of two patients infected with genotype 3a, the rate of liver steatosis was found to be high and did not change after IFN treatment in HD patients with CHC.     

Hepatitis C infection in hemodialysis patients: A review

Hepatitis C virus(HCV)-related liver disease is a significant cause of morbidity and mortality in patients with end-stage renal disease(ESRD) who is treated with dialysis or kidney transplantation(KT). The survival rate for HCV-infected renal transplant recipients is better than that for HCV-infected hemodialysis patients on transplant waiting lists. Early diagnosis and treatment HCV infection prior to KT prevents complications posttransplantation and reduces mortality. In addition to screening for anti-HCV antibodies and detecting HCV RNA, percutaneous liver biopsy is particularly valuable for assessing the stage of liver damage in HCV-infected patients, because the stage of fibrosis is importantdetermining optimal treatment for HCV. Studies have been demonstrated that with conventional interferon(IFN) monotherapy or pegylated IFN monotherapy are similar efficacy and safety in HCV-infected hemodialysis patients. Sustained viral responses(SVRs) with these monotherapies have ranged approximately 30% to 40%. Limited reports support the use of IFN and ribavirin combination therapy as antiviral treatment for ESRD patients or patients on hemodialysis. Ribavirin can be started at low dose and careful monitoring for side effects. Patients that show SVR after treatment are strong candidates for KT. It is also generally accepted that ESRD patients with decompensated cirrhosis and portal hypertension should be referred to the liver transplant team for consideration of combined liver-KT.     

Chronic infection with hepatitis C virus in patients with elevated or persistently normal serum alanine aminotransferase levels: comparison of hepatic histology and response to interferon therapy

Ninety-five patients with chronic hepatitis C virus (HCV) infection, 35 with persistently normal serum alanine aminotransferase (ALT) levels, were randomized to treatment with daily interferon (IFN) for 3 months, followed by IFN 3 times weekly (TIW) for 12 months (group A) or TIW for 18 months (group B). Patients with elevated versus normal ALT levels had similar demographic and virologic characteristics but significantly (P<.05) more advanced liver histology (bridging fibrosis and cirrhosis, 37.9% vs. 11.4%). After 3 months of treatment, 38.3% of patients in group A were HCV RNA negative versus 18.8% in group B (P<.05). When the IFN dose was reduced from daily to TIW in group A, the percentage of patients who remained HCV RNA negative declined; sustained virologic response was similar in both groups (10.6% vs. 8.3%). Response to treatment was similar in patients with elevated or normal ALT levels. Persons with chronic HCV infection and persistently normal serum ALT levels have milder liver disease than, and respond to IFN therapy similarly to, persons with elevated ALT levels.     

Combination of interferon and ribavirin in chronic hepatitis C: re-treatment of nonresponders to interferon

Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver failure, and hepatocellular carcinoma. A minority of patients have a sustained response to antiviral therapy, and nonresponders remain at risk of developing progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone. A total of 124 patients were randomized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained virologic response (undetectable HCV RNA at the 24-week follow-up point). This was associated with significant improvement in necroinflammatory activity noted on liver biopsy. Interestingly, there was not a statistically significant difference in response rates based on the duration of treatment; HCV genotype was the strongest predictor of a sustained response. Sustained responses were noted even in patients with poor predictive factors, including those with advanced hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. The study included 24 patients with normal serum alanine transaminase (ALT) values before therapy who had similar responses to those with initially elevated transaminase values. This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone.     

Hepatitis C infection and the patient with end-stage renal disease

Hepatitis C virus (HCV) remains common in patients with end-stage renal disease (ESRD) and is an important cause of liver disease in this population. Acquisition of HCV infection continues to occur in dialysis patients because of nosocomial spread. The natural history of HCV in dialysis patients remains controversial because the course of HCV typically extends over decades, whereas dialysis patients have higher morbidity and mortality rates than those of the general population limiting long-term follow-up. However, recent reports suggest that HCV infection affects the survival of chronic dialysis patients as well as renal transplant (RT) recipients. The severity of preexisting liver disease on pretransplantation liver biopsy may provide useful prognostic information about clinical outcome after RT; liver biopsy should be incorporated in the evaluation and management of RT candidates with HCV. Recent surveys with long-term follow-up have documented adverse effects of HCV on patient and graft survival. Use of renal grafts from HCV-infected donors in recipients with HCV does not appear to result in a greater burden of liver disease albeit with short-term follow-up. There is only limited data about interferon (IFN) therapy in chronic dialysis patients, although sustained responses are reported. Preliminary data on IFN plus ribavirin therapy in dialysis patients with hepatitis C have given encouraging results, but randomized trials are needed. Interferon remains contraindicated post-RT because of concern about precipitating graft dysfunction.     

Hepatitis C Is Less Aggressive in Hemodialysis Patients than in Nonuremic Patients

Background and objectives: The severity of liver disease among hepatitis C patients on hemodialysis is controversial. The aim of this study was to compare the clinical, biochemical, and liver histologic characteristics of hepatitis C virus (HCV) in hemodialysis patients and in those with normal renal function.Design, setting, participants, & measurements: A case-control study was carried out with 36 HCV patients on hemodialysis and 37 HCV patients with normal renal function matched for gender, age at infection, and estimated time of infection.Results: HCV patients on hemodialysis had lower levels of alanina aminotransferase and lower viral load. Hepatic fibrosis was significantly higher in the patients with normal renal function (73%) than in hemodialysis patients (47.2%, P < 0.025); the same was observed for inflammatory activity (control group 59.5% versus hemodialysis patients 27.7%, P = 0.003). In addition, the risk of tissue inflammation was four times lower in hemodialysis patients (odds ratio = 0.23, P < 0.004), and severe inflammatory activity on biopsy was the only independent risk factor for fibrosis (P < 0.001).Conclusions: The lower biochemical and inflammatory activities observed in hemodialysis patients suggest that hemodialysis and uremia may have a protective role against progression of the disease caused by HCV.Hepatitis C is the main cause of chronic liver disease in patients with end-stage renal disease (ESRD). The prevalence of hepatitis C virus antibody (anti-HCV) is high, between 3.4% and 32.1%, among hemodialysis (HD) patients and potential kidney transplant candidates (1). Despite the decrease in the incidence of newly acquired HCV infections observed in recent years, which may be attributable to the efficient serologic HCV tests used in blood transfusions and to the use of erythropoietin to treat anemia, contamination by HCV still occurs in HD units (2).Patients infected with HCV who undergo renal transplantation show a higher risk for progression to severe liver disease, death, and graft failure after transplantation compared with anti-HCV negative recipients (3). Liver disease should consequently be staged at the time of kidney transplantation because patients with cirrhosis or advanced fibrosis will have a poorer prognosis (4).The natural history of chronic liver disease caused by HCV in HD patients remains unknown (4–6). HCV infection increases mortality rates in uremic patients, and cirrhosis and other liver-related deaths are more frequent in HCV-infected dialysis patients than in those without the virus (5–7).Results from liver biopsies of HCV-infected dialysis patients are limited (1,2), and the rate of bridging hepatic fibrosis and liver cirrhosis ranges from 5% to 32% (8–15). Whether the liver disease caused by HCV shows a different clinical course in HD patients and in patients with normal renal function is still controversial. Barril (8) reported that progression time to cirrhosis can be much shorter in HCV-infected HD patients than in patients with normal renal function. However, other studies suggest that HCV-infected HD patients present a lower degree of inflammatory activity and a lower stage of liver fibrosis compared with HCV-infected patients with normal renal function (9,12,15). Indeed, the effects of chronic uremia and HD on HCV-related liver disease and on the progression of liver fibrosis in HCV-infected patients with ESRD remain unknown.To investigate the impact of chronic renal failure and HD on the progression of hepatitis C in patients awaiting kidney transplantation, we compared clinical, biochemical, virologic, and histologic findings in HCV-infected patients with ESRD receiving HD treatment and in HCV-infected patients with normal renal function. Our results showed that HCV-infected patients on HD presented lower levels of alanine aminotransferase (ALT), lower viral load, and less inflammatory activity and fibrosis in their liver biopsies. Moreover, severe inflammatory activity was the only independent risk factor for liver fibrosis. Taken together, our results strongly suggest that chronic hepatitis C is less aggressive in HD patients than in nonuremic patients.     

Hepatitis C virus NS5A inhibitors and drug resistance mutations

Some direct-acting antiviral agents for hepatitis C virus(HCV),such as telaprevir and boceprevir have been available since 2011.It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis.HCV NS5A inhibitors efficiently inhibited HCV replication in vitro.Human studies showed that dual,triple and quad regimens with HCV NS5A inhibitors,such as daclatasvir and ledipasvir,in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin,could efficiently inhibit HCV replication according to HCV genotypes.These combinations might be a powerful tool for"difficult-to-treat"HCV-infected patients."First generation"HCV NS5A inhibitors such as daclatasvir,ledipasvir and ABT-267,which are now in phaseⅢclinical trials,could result in resistance mutations."Second generation"NS5A inhibitors such as GS-5816,ACH-3102,and MK-8742,have displayed improvements in the genetic barrier while maintaining potency.HCV NS5A inhibitors are safe at low concentrations,which make them attractive for use despite low genetic barriers,although,in fact,HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors,HCV NS5B inhibitors or peginterferon plus ribavirin.This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.     

Usefulness of combined application of double‐filtration plasmapheresis and twice‐daily injections of interferon‐β in hemodialysis patients with hepatitis C virus genotype 1b infection and a high viral load

Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and has been recognized as an important prognostic factor. Therefore, the aggressive antiviral therapy is necessary for HCV infection in HD patients. However, various treatment limitations exist in HD patients such as the inability to use ribavirin. We have previously reported that HCV RNA can be eradicated by administration of interferon (IFN)‐β during HD in patients with HCV infection caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA levels. In this case report, we tried to clarify the efficacy of combined application of double‐filtration plasmapheresis (DFPP) and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. We report two HD patients with HCV genotype 1b infection and high viral loads who were successfully treated by five sessions of DFPP undertaken prior to treatment with IFN‐β (twice‐daily injections for 2 weeks). HCV was eradicated by this combination therapy in both patients. We revealed the efficacy of combined application of DFPP and IFN‐β in HD patients with HCV genotype 1b infection and high serum HCV RNA levels. This combined therapy may be useful for the HD patients who are resistant to conventional IFN monotherapy.     

Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection

OBJECTIVE: To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV). DESIGN: Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy. METHODS: We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNgamma and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning. RESULTS: There were significant negative correlations between inflammatory scores and IFNgamma production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNgamma production in response to NS5 and summed HCV proteins. Higher IFNgamma production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNgamma responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNgamma response to Candida. CONCLUSIONS: In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNgamma responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.     

Clinical implications of TT virus superinfection in patients with chronic hepatitis C

OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E hepatitis virus. We investigated superinfection of TTV in patients with chronic hepatitis C and studied the susceptibility to interferon (IFN) treatment and its association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV DNA was examined using the seminested polymerase chain reaction (PCR), and its virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was detected in 20 of 102 (19.6%) patients examined. There was no significant difference in the alanine aminotransferase (ALT) level between patients with or without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV were sensitive to IFN therapy. Complete response to IFN with a sustained loss of viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%) patients with respect to TTV DNA and in five of 20 (25%) patients with respect to HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the complete-response cases than in the no-response cases, but there was no significant difference in the pretreatment TTV DNA levels between them. ALT normalization resulting from IFN therapy was not attributable to the eradication of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not influence the effect of IFN against HCV. No specific TTV genotype correlating with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV infection stands independent of HCV infection, with no influence on liver injury as a result of HCV infection.     

Can zinc enhance response interferon therapy for patients with HCV-related liver disease?

Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease. The standard of care for chronic HCV has improved markedly since the approval of interferon (IFN) therapy more than a decade ago. Over the past 20 years, IFN therapy has improved to more effectively eliminate the virus, progressing from single IFN therapy to combination therapy with ribavirin (RBV) and finally to pegylated IFN (PEG-IFN) therapy. However, even combined therapy with PEG-IFN and RBV for 48 wk is unable to eliminate the virus in some 40% of hepatitis C cases, particularly those with genotype 1b and high viral load. Treatment options for patients who have relapsed or are refractory to treatment with PEG-IFN and RBV therefore need to be critically assessed. This paper overviews the relationship between chronic liver disease and zinc metabolism.     

Fibrosing cholestatic hepatitis with hepatitis C virus treated by double filtration plasmapheresis and interferon plus ribavirin after liver transplantation

Fibrosing cholestatic hepatitis (FCH) is a serious disease in patients with recurrent hepatitis C after liver transplantation (LTx). Antiviral therapy is indicated in these patients; however, it is not always effective, and the prognosis of FCH is generally poor. Double filtration plasmapheresis (DFPP) has been shown to be effective at eliminating hepatitis C virus (HCV) in patients with chronic hepatitis C. We report a case of FCH with severe cholestasis (total bilirubin 34.2 mg/dl) after LTx. Combination therapy with interferon (IFN) and ribavirin (RBV) was unsuccessful for improving cholestasis; however, the addition of DFPP to IFN and RBV alleviated cholestasis and improved renal function. Although IFN and RBV with DFPP could not eliminate HCV, results of liver function tests improved and remained stable for several months. This treatment with DFPP combined with IFN and RBV would be useful for resolving cholestasis due to FCH. Moreover, treatment of DFPP could improve liver and renal function test results and could stop the worsening condition of patients with FCH.     

Histological response to interferon alfa-based therapies in hepatitis C

Histological response is defined as an improvement in the severity of liver inflammation with or without an improvement in fibrosis in patients following treatment for an acute or chronic liver disorder. Histological response occurs in patients with chronic hepatitis C virus (HCV) infection who have had a sustained virological response following treatment with interferon (IFN) therapy and in a percentage of nonresponders. Continuing IFN long term as maintenance therapy has been shown to prevent histological progression in patients who had both a marked decline in serum HCV RNA level during treatment and a histological response on repeat histological analysis. Prospective controlled trials are currently evaluating the benefits of low-dose maintenance therapy with pegylated IFN in HCV patients who have failed to achieve sustained virological response. In the future, the development of serum markers of fibrosis may allow for monitoring of hepatic fibrosis and histological response to therapy without the need to perform repeat liver biopsy.