Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

Recurrent hepatitis C is often treated with an interferon and ribavirin combination therapy, but the results have been disappointing. Given the promising results reported with pegylated interferon and ribavirin for hepatitis C, we were interested in evaluating the effectiveness of this treatment in liver transplant recipients with recurrent hepatitis C (HCV). METHODS: Between November 2001 and September 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Liver function tests, HCV-RNA, and liver biopsies were performed on all patients prior to treatment. HCV-RNA was repeated at 3 months, the end of treatment (EOT), and 6 months after EOT for patients who were HCV-RNA negative at EOT. Patients were prospectively followed after starting weekly pegylated interferon alfa-2b 1.5 mcg/kg per week and ribavirin 800 mg per day (Schering-Plough, Kenilworth, NJ, USA) with folic acid 1 mg per day. RESULTS: Thirty-nine patients eligible for treatment displayed a median age of 50.4 years. Eighteen patients completed treatment, 4 remain on treatment, and 17 were intolerant. Sustained HCV-RNA eradication occurred in 66.7% of patients who completed treatment. Side effects led to treatment withdrawal in 17 patients (43.6%) In an intention-to treat analysis, sustained HCV-RNA eradication occurred in 30.8% of patients. CONCLUSION: Side effects are an important limiting factor in the treatment of recurrent HCV with pegylated interferon and ribavirin. However, these results are encouraging as sustained HCV eradication occurred in at least 66.7% of patients who completed treatment. Prospective randomized trials are required to assess the effectiveness of this treatment and its impact on quality of life and histology.     

A Pilot Study: Longer Duration of Posttransplant Hepatitis C Virus Therapy May Increase the Sustained Response Rate

Background

Although end of treatment virological responses are similar in posttransplant patients with recurrent chronic hepatitis C virus infection and nontransplant patients, the sustained virological response rate is lower in the posttransplant setting. We investigated the efficacy of a longer duration (3 years) of therapy.

Methods

Thirteen patients with biopsy-proven recurrent hepatitis C were included in the study. In the first year of therapy, all patients were treated with a standard regimen of interferon alpha 2b 3MU 3 times in a week plus ribavirin (800 to 1000 mg/d). After the availability of pegylated interferon, patients were converted to pegylated interferon (1.5 μg/kg body weight). Hepatitis C virus RNA was evaluated at months 3, 6, 9, 12, 24, 36, and 42. If hepatitis C virus RNA was negative at month 12, the patients continued treatment for 36 months.

Results

Hepatitis C virus RNA was negative in six patients at 12 months, including two who became hepatitis C virus RNA negative after 3 months; two, after 6 months; and two, after 12 months of therapy. Those six continued treatment completing 3 years of treatment with a sustained virological response. Four of those six patients with sustained virological response required colony-stimulating factors during treatment.

Conclusion

Although the hepatitis C virus RNA status of patients at 12 weeks is a good marker to predict a sustained virological response in the nontransplant setting, it is not valid in posttransplant patients. A prolonged duration of therapy for patients who are viral responders at 12 months may prevent recurrence and increase the sustained virological response rate.     

Successful rescue of severe recurrent hepatitis C with interferon and ribavirin in a liver transplant patient

BACKGROUND: Rapid graft dysfunction caused by hepatitis C virus (HCV) reinfection, although uncommon, is a disastrous complication in liver transplant patients. Finding an effective therapy for this subgroup of patients with severe recurrent HCV is a priority. METHOD: We describe a successful rescue of a 46-year-old man with recurrent hepatitis C (HCV genotype 1b) using long-term interferon (IFN) and ribavirin. The patient had a very aggressive type of posttransplantation HCV infection, as judged by biochemical and histologic findings. RESULTS: Despite high pretreatment values of serum alanine aminotransferase (ALT; peak value of 901 IU/L) and HCV-RNA (2.3 x 10(6) copies/ml), the combination therapy with IFN and ribavirin produced a rapid normalization of the serum ALT values, accompanied by the clearance of serum HCV-RNA. Although HCV-RNA reappeared in the serum at 3 months, the patient had continued ALT normalization and histological improvement with follow-up of over 26 months to date after the initiation of the combination therapy. CONCLUSION: This observation suggests that IFN in combination with ribavirin may offer an effective therapeutic option for liver transplant patients with severe recurrent hepatitis C.     

Utilization of a liver allograft from a hepatitis B surface antigen positive donor

With today's donor organ shortage, enhanced efforts must be made to utilize organs that previously would have been declined. We report a 26-year-old man with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection who received a liver transplant from an HBsAg-positive donor. HBV viremia (6,281,185 copies/ml) was seen early posttransplant despite lamivudine prophylaxis, but became negative with addition of adefovir. Virologic analysis revealed predominantly donor HBV strain immediately posttransplant. At 5 months there was an elevation of liver enzymes accompanied by histologic evidence of hepatitis. At this time, HCV-RNA was positive but HBV DNA was undetectable. Treatment with pegylated interferon and ribavirin resulted in sustained clearance of HCV RNA. Two years posttransplant, the patient has normal liver biochemistry and HCV and HBV viral load are undetectable with persistence of HBsAg. Our experience suggests that with effective antiviral therapy, the use of HBsAg seropositive donors is feasible in selected circumstances.     

Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin

BACKGROUND: Recurrent hepatitis C virus (HCV) after liver transplantation (OLT) is a major cause of graft loss in HCV-positive patients. In this study, we evaluated the efficacy and safety of pegylated interferon alfa-2b (peginterferon) and ribavirin treatment for recurrent HCV after OLT and analyzed the influence of antiviral treatment on the histological course of recurrent hepatitis. METHODS: Twenty-five patients with recurrent HCV (genotype 1 n=20 and 2-4 n=5) received peginterferon (1 mg/kg/weekly) and ribavirin (600 mg) for 48 weeks. Viral load prior to treatment was below 1,000,000 (IU/ml) in 11 of 25 patients. Sustained antiviral response was defined as undetectable HCV-RNA in serum 6 months after stopping of therapy. All patients underwent liver biopsy prior to treatment and after 72 weeks. RESULTS: Seventeen of 25 patients became HCV-RNA-negative after treatment (68%). Sustained virologic response (SVR) was achieved in 9/25 (36%) patients. Liver specimen showed increase of fibrosis from 1.7 to 2.0 within 72 weeks. Side effects like neutropenia (60%) and anemia (36%) were treated with G-CSF, erythropoietin, and dose reduction of peginterferon and ribavirin. CONCLUSIONS: The use of peginterferon is safe and effective in patients with recurrent HCV. Treatment of side effects, especially neutropenia or anemia, helped to maintain antiviral therapy. Despite a viral response of 68% during treatment, the patients showed further progress of recurrent hepatitis in liver specimen.     

Chronic hepatitis C virus infection in renal transplant: treatment and outcome

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C. METHODS: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400-800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 microg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period. RESULTS: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 +/- 147.6 and 104.8 +/- 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 +/- 114.9 IU/L at baseline to 71 +/- 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy. CONCLUSION: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment.     

Superiority of standard interferon-alpha2b compared to pegylated interferon-alpha2b (12 kDa) in a hemodialysis patient with chronic hepatitis C?

INTRODUCTION: Hepatitis C virus (HCV) infection represents an important problem for hemodialysis patients. Interferon-alpha (IFN-alpha) three times per week has been shown to clear HCV RNA in a substantial proportion of renal transplant candidates, and may thereby prevent the deleterious effect of immunosuppressive treatment on progression of liver disease in HCV-positive patients after renal transplantation. Data on the efficacy of the new pegylated interferons in hemodialysis patients are limited and general recommendations are absent. CASE: A 41-year-old Caucasian man infected with hepatitis C genotype 1b was admitted with a history of renal transplantation in 1990, and reintroduced hemodialysis in 1997 because of chronic rejection. Antiviral therapy with pegylated interferon-alpha2b (120 microg/oiw) and ribavirin (400 mg/tiw) was initiated. A virological and biochemical response with undetectable HCV-RNA was evident already after six weeks. Two weeks later, however, HCV-RNA became detectable again with 18.000 IU/ml. The treatment regimen was changed to standard-IFN-alpha2b (3 MU/tiw). Shortly thereafter, ribavirin had to be withdrawn because of severe anemia. After three weeks, hemoglobin level rebounded to values higher than 10 g/dl and a lower dose of ribavirin (200 mg/tiw) could be reintroduced. Virological and biochemical response occurred after switching to standard interferon-alpha2b within three months with good tolerance of antiviral combination treatment until the end of 48 weeks of therapy. The patient remained HCV-RNA-negative throughout follow-up of 36 weeks. ALT levels are still within normal limits and the patient is now waiting for a kidney transplantation. CONCLUSION: Considering the treatment course of this patient, IFN-alpha2b three times per week directly after hemodialysis seems to be superior to pegylated interferon-alpha2b once weekly in this case. The role of pegylated IFN-alpha2a for dialysis patients remains to be investigated.     

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 microg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy.     

Treatment of chronic hepatitis C in Europe

The lifetime cumulative risk of developing cirrhosis and hepatocellular carcinoma is the rationale for treating patients with chronic hepatitis C with antivirals. The standard treatment is combination therapy with interferon-alfa and ribavirin. In patients with high transaminases and histologic signs of chronic hepatitis, 6- to 12-month therapy with 3 mega units (MU) interferon-alfa thrice weekly, combined with ribavirin, yielded up to 30% sustained responders, and this was increased to 50% with pegylated interferon combined with ribavirin. Favorable predictors of response to the former treatment were genotype 2 or 3, less than 2 million copies of hepatitis C virus (HCV), no portal fibrosis at biopsy, age less than 40 years, and female sex. The same was true for the latter treatment; however, with body weight less than 82kg replacing female sex. A 98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5MU interferon, compared with a calculated 30% HCV-RNA clearance in untreated patients. More cost-effective strategies for ceasing treatment, based upon early clearance of HCV, are under investigation, with cutoff equal to or more than a 2log decrease in serum HCV-RNA at week 12. This approach has 100% negative predictive value and 80% positive predictive value. Treatment can also be optimized by combination retreatment of relapsers and nonresponders to monotherapy, which yielded sustained responses of 50% and 25%, respectively. There are difficult-to-treat patients who have high viremia, genotype 1 and 4, or coinfection with HIV or HBV, or carry an organ graft, and those who did not respond to combination therapy. Extended treatment of the latter patients with pegylated interferon might slow down the progression of fibrosis.     

Effect of poverty and other socioeconomic variables on renal allograft survival

BACKGROUND: Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients. Standard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients. METHODS: Twelve patients, at least 7 months posttransplant, with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were randomized to interferon-alpha2a, 3 mU daily for 12 months (n=8) or no treatment (n=4). The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. RESULTS: Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus median increase of 1.5) (P=0.04). Four treated patients had a virological response (all bDNA negative, one qualitative polymerase chain reaction negative) compared with none of the untreated patients. Only two of six treated patients tested had evidence of quasispecies diversification on therapy. Seven of eight patients in the treatment group required dose reduction for fatigue and/or depression. They tolerated 1.5 mU of interferon-alpha2a daily. Two treated patients developed graft dysfunction, one of who had histological evidence of rejection and subsequent graft loss. CONCLUSIONS: Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases. These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant.     

Histological Benefit of Retreatment by Pegylated Interferon Alfa-2b and Ribavirin in Patients with Recurrent Hepatitis C Virus Infection Posttransplantation

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.     

Early diagnosis and treatment resolved cholestatic hepatitis C without fibrosis after living donor liver transplantation: Report of a case

Cholestatic hepatitis is a life-threatening recurrent pattern of hepatitis C virus (HCV) in immunosuppressed patients, for which curative treatment has not yet been established. We report the successful treatment of cholestatic hepatitis in a 59-year-old man who had undergone right lobe living donor liver transplantation (LDLT) for liver cirrhosis (LC) caused by HCV. Following uneventful surgery and an uncomplicated posttransplant clinical course, there was an abrupt increase in total bilirubin in comparison to aminotransferase on postoperative day (POD) 60 (total bilirubin 16.2 mg/dl, alanine aminotransferase 100 U/l, HCV-RNA 390 kIU/ml). The histological findings of the liver tissue showed lymphocyte infiltration in the periportal zone and severe cholestasis. Considering the clinical course, cholestatic hepatitis was strongly suspected and pegylated interferon and ribavirin therapy was started immediately, resulting in not only a viral response, but minimal progression of fibrosis. This case serves to demonstrate that early diagnosis and timely initiation of optimal antiviral therapy is essential for the resolution of cholestatic hepatitis C.     

De novo autoimmune hepatitis subsequent to switching from type 2b to type 2a alpha-pegylated interferon treatment for recurrent hepatitis C after liver transplantation: report of a case

Interferon (IFN), which is the only possible agent for recurrent hepatitis C after liver transplantation, may cause serious immune-related disorders. We report a case of de novo autoimmune hepatitis (AIH), which developed subsequent to switching from 2b pegylated interferon-α (peg-IFN) to 2a peg-IFN after living donor liver transplantation (LDLT). A 51-year-old man with hepatitis C-associated liver cirrhosis underwent LDLT. About 13 months after the initiation of antiviral therapy, in the form of type 2b peg-IFN with ribavirin, a negative serum hepatitis C virus (HCV)-RNA titer was confirmed. Thereafter, the 2b peg-IFN was switched to 2a peg-IFN, 3 months after which severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy showed portal and periportal inflammatory infiltrates including numerous plasma cells, indicating AIH. He was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance, but eventually died of Pneumocystis pneumonitis 4 months after the diagnosis of de novo AIH.     

Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy

INTRODUCTION: The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective. We present data from a retrospective review in liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin. METHODS: A retrospective review of transplant recipients that received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) therapy intended for at least 48 weeks. Complications were recorded and included neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression. The diagnosis of HCV recurrence was determined by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test. RESULTS: Fifty-seven liver-transplant recipients were included, 29 naive (group 1) to therapy and 28 nonresponders (group 2) to at least 6 months of interferon and ribavirin therapy. Eight (27.6%) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy. Ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2. Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim. CONCLUSION: Combination pegylated interferon with ribavirin appears to effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin. This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy.     

Pegylated interferon-α-based treatment for chronic hepatitis C in renal transplant recipients: an open pilot study

Treatment of hepatitis C in renal transplant recipients remains a controversial issue, as interferon therapy has been associated with a high risk of rejection and poor efficacy. We report here the use of pegylated interferon-α, alone or in combination with ribavirin, in renal transplant recipients with chronic hepatitis C. Eight renal transplant recipients with chronic hepatitis C were recruited. The mean delay between renal transplantation and antiviral therapy was 198.8 months. Sustained virological response was observed in four of out eight patients. Three patients with sustained virological response were genotype 2, one was genotype 1; fibrosis stages were F1 for one patient, F2 for 2, F3 for one. At baseline, renal dysfunction was moderate in seven patients and severe in one patient. No patient experienced rejection episodes during or after pegylated interferon-α therapy. One patient developed haemolytic uraemic syndrome, which eventually resulted in graft loss and return to dialysis. In conclusion, for renal transplant recipients treated with pegylated interferon-α-based therapy, we observed a low risk of renal dysfunction, acceptable tolerance and significant virological efficacy. This is therefore the first study to suggest that pegylated interferon-α could be proposed late after transplantation to renal transplant recipients.     

The effect and safety of the treatment of recurrent hepatitis C infection after orthotopic liver transplantation with pegylated interferon α2b and ribavirin

Introduction

Recurrent hepatitis C infection in the posttransplant setting is a serious problem. The aim of this study was to evaluate the efficacy, safety, indications, optimal time of administration and adequate duration of antiviral therapy with pegylated interferon alpha 2 b (PEG-IFN) and ribavirin (RIB).

Patients and methods

Between 2003 and 2009, 16 patients received antiviral therapy (PEG-IFN: 0.8–1.6 μg/kg/wk, RIB 800–1200 mg/d) for at least 6 months. Patients with a biochemical without a virologicalresponse after 12 months of therapy received antiviral treatment for a further 6 months. Hepatitis C virus load was determined at 1, 3, 6, and 12 months after start of therapy. Liver biopsy was performed in all patients before the beginning and after the end of treatment.

Results

The mean period of antiviral therapy was 14 months. The four patients who received the full-length treatment (12 months, 33%) showed sustained virological responses (SVR) and 8 showed virological and biochemical responses (VR, BR). Patients with SVR showed significant improvement in the grading and staging of HAI (histological activity index; P = .03). Nine patients had several side effects under antiviral treatment. Acute rejection episodes were not observed.

Conclusion

The antiviral treatment combination using PEG-IFN and RIB for recurrent hepatitis C is effective procedure. The SVR of 33% after 12 months of treatment with significant improvement in HAI grading and staging and stable HAI in all treated patients favor early initiation and 12-month administration of antiviral treatment. Furthermore, all patients with BR without VR, who underwent antiviral treatment for a further 6 months, achieved a VR. However, the optimal duration of treatment needs to be investigated in large prospective studies.     

Pegylated interferon alfa-2a and ribavirin for recurrent hepatitis C after liver transplantation

BACKGROUND: Recurrent hepatitis C virus (HCV) is often treated with interferon and ribavirin combination therapy but results have been disappointing. Given the promising results reported with pegylated interferon and ribavirin for hepatitis C, this combination is now preferred for the treatment of recurrent HCV. This article reports a transplantation program's experience with antiviral therapy treatment for liver transplant recipients with recurrent HCV. METHODS: Between October 2002 and June 2004, patients with recurrent HCV were screened to determine if they were eligible for treatment. Liver function tests, HCVRNA, and liver biopsies were done on all patients prior to treatment. HCVRNA was repeated at 3 months, end of treatment (EOT), and 6 months after EOT for patients HCVRNA-negative at EOT. Patients were prospectively followed up after starting weekly pegylated interferon alfa-2a 180 mcg/wk and ribavirin 1000-1200 mg/d (Roche, Nutley, NJ, United States) with folic acid 1 mg/d. RESULTS: Thirty-two patients were eligible for treatment with a median age of 49.2 years. Twenty-one patients have completed treatment, 6 remain on treatment, and 5 were intolerant. In an intention-to-treat analysis, sustained HCVRNA eradication occurred in at least 40.6% of patients. Side effects led to treatment withdrawal in 5 patients (15.6%). CONCLUSION: Pegylated interferon alfa-2a and ribavirin appear promising for the treatment of recurrent HCV. Side effects were an infrequent cause of treatment discontinuation, unlike previous combinations of interferon-based therapy. Randomized, prospective trials incorporating serial liver biopsies with appropriate quality of life analyses are required to manage this silent epidemic.     

Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with renal manifestations, such as membranoproliferative glomerulonephritis (MPGN) with or without cryoglobulinaemia, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS). Standard treatment for HCV is interferon and ribavirin, but in renal insufficiency ribavirin has been contraindicated due to fear of side effects. METHODS: Seven patients, two with cryoglobulinaemia, vasculitic manifestations and glomerulonephritis (GN), four with MPGN and one with FSGS were treated with a combination of interferon and ribavirin. Two patients were given pegylated interferon and ribavirin. All patients had at presentation renal insufficiency, with a glomerular filtration rate (GFR) between 10 and 65 ml/min. One patient had HCV genotype 1, the remainder 2 and 3. Duration of therapy was according to genotype (6-12 months). Ribavirin in plasma was monitored by high-performance liquid chromatography (HPLC) to avoid over-dosing, aiming at a target concentration of 10-15 micromol/l. The main side effect of ribavirin, haemolytic anaemia, was monitored closely with haemoglobin controls. RESULTS: Six of seven patients became HCV-RNA-PCR negative and four of seven have maintained both virological and renal remission. One of seven has maintained virological and partial renal remission. One patient did not tolerate interferon, but is in renal remission with low-dose ribavirin. One vasculitis patient responded with complete remission, but relapsed virologically and had a minor vasculitic flare after 9 months. Only one patient with vasculitis had low-dose immunosuppression in addition to anti-viral therapy. Average daily ribavirin dose was 200-800 mg. Ribavirin-induced anaemia was managed in five of seven patients with low-dose iron and erythropoietin between 4000 and 20 000 IU/week. CONCLUSIONS: Interferon and ribavirin can with reasonable safety be used in HCV-related vasculitis and GN irrespective of renal function.     

维持性血液透析患者合并慢性丙型肝炎的治疗新体会

目的探讨苦参素治疗维持性血液透析患者合并慢性丙型肝炎的效果、不良反应。方法收集维持性血液透析合并慢性丙型肝炎患者26例,随机分为治疗组和对照组,每组13例。治疗组给予聚乙二醇干扰素α -2a 180μg,肌肉注射,每周1次,疗程6个月,联合苦参素葡萄糖注射液100ml静滴3个月。对照组仅给予聚二醇干扰素α -2a 180μg,肌肉注射,每周1次,疗程6个月。观察治疗后12周、24周及停药后随访24周血清丙型肝炎病毒-RNA滴度中位数水平及丙型肝炎病毒-RNA阴转率,同时观察治疗前、后不良反应。结果治疗组丙氨酸氨基转移酶下降程度及丙型肝炎病毒RNA阴转率均高于对照组,同时不良反应低于对照组。结论苦参素在促进肝功能恢复、抑制丙肝病毒复制方面具有一定疗效,而且不良反应小,患者耐受性好。