Liver-kidney recipients with chronic viral hepatitis C treated with interferon-alpha

Antiviral therapy with interferon-alpha (IFN-alpha) and pegylated IFN-alpha (PEG-IFN-alpha) for chronic hepatitis C (HCV)-infected kidney recipients remains controversial. IFN-alpha is not recommended in most cases because it induces severe acute graft rejection. However, IFN-alpha, as PEG-IFN-alpha, is associated with a more pronounced immune response, and is well tolerated in HCV-infected liver recipients without causing graft rejection. In combined liver-kidney transplant (LKT) recipients, IFN-alpha has been occasionally used and appears to be well tolerated. All LKT recipients with a functioning kidney and liver having a HCV replication and who needed IFN-alpha therapy have been included in the study. The occurrence of liver and/or renal acute rejection as well as the HCV replication has been collected. A total of 12 LKT patients treated with PEG-IFN-alpha plus ribavirin have been studied. No acute rejection was observed. Renal function remained stable during and after discontinuing treatment, without any graft dysfunction. Two patients had a partial viral response and four had a sustained viral response. All patients, whatever their viral response, had decreased liver-enzyme levels. Response to PEG-IFN-alpha therapy was correlated with steroid dose and transaminase level when PEG-IFN-alpha was started. These data suggest that the combination therapy of PEG-IFN-alpha plus ribavirin did not have a higher risk of acute kidney-graft rejection after liver-kidney transplantation.     

Hepatitis C virus-related cryoglobulinemic glomerulonephritis: long-term remission after antiviral therapy

BACKGROUND: Renal involvement in patients with hepatitis C virus (HCV) infection commonly manifests as cryoglobulinemic glomerulonephritis (CGN). The combination of interferon-alpha (IFN-alpha) and ribavirin, which is currently considered the standard antiviral therapy in chronic hepatitis C, could be difficult to carry out in cryoglobulinemic patients who are frequently anemic, even in the absence of renal failure. Clinical and histologic long-term results of this therapeutic regimen have not been so far reported in patients with CGN. METHODS: Three patients with HCV-related CGN and slightly impaired kidney function were treated with IFN-alpha and ribavirin for 12 months, and subsequently were followed up for 24 to 36 months. Two of these patients who were anemic were pretreated with erythropoietin (EPO). In each patient renal biopsy was performed before starting therapy and repeated 14 to 26 months after the end of treatment. RESULTS: In all three patients, antiviral therapy induced sustained virologic response, which was followed by clear improvement in clinical, biochemical, immunologic, and histologic features. Clinical and biochemical improvement steadily progressed in all three patients, achieving normal or nearly normal results at the end of follow-up. In contrast, some immunologic features, such as serum levels of C4 and rheumatoid factor activity, did not normalize in two and three patients, respectively. Posttreatment renal biopsies showed mildly active histologic lesions. CONCLUSION: Antiviral therapy with IFN-alpha and ribavirin may be considerably beneficial in patients with HCV-related CGN who obtain sustained virologic response.     

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.     

Seizures during the treatment with interferon for chronic C hepatitis

Interferon alpha (IFN-alpha) is a well-established first-line treatment for chronic viral hepatitis. Side effects of IFN-alpha therapy are common but generally mild and self-limited. Generalized seizures during IFN-alpha therapy are very uncommon and are present in clinical isolated cases and usually in association with high doses of IFN-alpha. In our case a female of 39 years old, seizures have occurred at low doses of IFN-alpha used as therapy for chronic C viral hepatitis. As it comes to our knowledge, till now, there were published only 4 cases of generalized seizures that occurred during treatment with IFN-alpha for chronic C viral hepatitis. The physiopathology of this complication is unknown. Generalized seizures can be reasonable due to IFN-alpha therapy, as long as the patient didn't have any seizure history, or other factors, which can develop seizures. Neurological examination, EEG and brain scan were normal. The recurrence of these seizures was absent stopping IFN-alpha therapy without any other seizure 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.     

Sustained response with negative serum HCV-mRNA and disappearance of antibodies after interferon-alpha therapy in a kidney transplant recipient with chronic active viral hepatitis C

BACKGROUND: The use of interferon-alpha (IFN-alpha) to treat viral hepatitis C (HCV) occurring in kidney transplant recipients is controversial. This study reports an HCV patient successfully treated with IFN-alpha therapy achieving sustained response, negative serum HCV-mRNA and the disappearance of HCV antibodies, without impairment of renal function. METHOD: A young kidney transplant recipient developed a proven HCV infection 70 months post-transplantation. The patient received IFN-alpha therapy, and for a 32-month follow-up period was evaluated clinically, serologically and virologically. RESULTS: IFN-alpha therapy resulted in normal transaminase activities within 2 months. Serum HCV-mRNA was negative after 4 weeks of treatment and is still negative. Ten months after IFN-alpha therapy withdrawal, the enzyme immunoassay revealed that HCV antibodies (HCVAb) were absent in the serum. IFN-alpha therapy was safe, well tolerated and renal function was not impaired.     

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.     

Recurrent hepatitis C after liver transplantation: A nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin

Liver transplant recipients with recurrent hepatitis C virus (HCV) infection often have histological hepatitis, and in some patients, graft failure develops. The aim of this nonrandomized study is to determine the efficacy and tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavirin combination therapy in such patients. Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times weekly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary end points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy. End-of-treatment biochemical responses were similar in the two groups (IFN alfa, 20% v combination therapy, 25%); however, viral clearance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IFN-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantly in both groups during therapy. There was no improvement in inflammatory grade, and fibrosis score was worse in both groups. Ten patients (25%) in the IFN-alfa group and 5 patients (20%) in the combination-therapy group withdrew because of adverse effects. We conclude that in liver allograft recipients with recurrent hepatitis C, combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability. (Liver Transpl 2001;7:863-869.)     

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.     

A laparoscopic splenectomy allows the induction of antiviral therapy for patients with cirrhosis associated with hepatitis C virus

It is difficult to treat patients with cirrhosis-associated hepatitis C with pegylated interferon (PEG-IFN) and ribavirin because of thrombocytopenia-related hypersplenism. Both safety and clinical efficacy were retrospectively analyzed for patients who underwent a laparoscopic splenectomy (LS) from January 2003 to December 2007. A total of 35 patients with cirrhosis associated with hepatitis C virus had LS for thrombocytopenia before PEG-IFN and ribavirin therapy, and all patients had thrombocytopenia, which was a contraindication for antiviral therapy. The hepatopathy was Child A in 24 patients, Child B in 10 patients, and Child C in one patient. All 35 patients increased platelet count from 48,000 +/- 15,000 to 155,000 +/- 55,000/microl (P < 0.0001) after LS. The median hospital stay and blood loss were 13.0 days (range, 8 to 57 days) and 342.0 mL (range, 5 to 2350 mL). There was no postoperative death. Twenty-nine (83%) patients had PEG-IFN and ribavirin therapy after LS; 18 had complete therapy and 11 had partial therapy. Of these, nine had a sustained virologic response. A laparoscopic splenectomy for patients with cirrhosis associated with hepatitis C virus can be performed safely and allows induction of antiviral treatment.     

Development of porphyria cutanea tarda in a hemodialysis patient after reactivation of hepatitis C virus infection

Cases of porphyria cutanea tarda (PCT) are occasionally reported in hemodialysis patients. Recently, hepatitis C virus has been recognized as a precipitating factor of PCT. The activity of the liver disease may be critical for the appearance of PCT. In this regard, liver disease reactivation after treatment with interferon alpha (IFN-alpha) is a well-known phenomenon. We report the case of a hemodialysis patient who developed PCT coincidentally with reactivation of liver disease, immediately after treatment with IFN-alpha. Therefore, in the present case, reactivation of hepatitis after IFN-alpha withdrawal could be the triggering factor. The occurrence of a bout of PCT should be considered as a possible complication at the end of IFN-alpha therapy, if reactivation of the disease exists.     

Ribavirin, but Not Interferon α-2b, is Associated with Impaired Osteoblast Proliferation and Differentiation In Vitro

Hepatitis C treatment with interferon alpha-2b (IFN-alpha) and ribavirin has been related to decreased bone mineral density. The aim of this study was to investigate the in vitro effects of different concentrations of ribavirin and IFN-alpha on osteoblast-like cells. Human osteoblast-like cells obtained by the outgrowth of cells from bone chips were exposed to ribavirin (0.1-10 microg/mL) or IFN-alpha (0.1-1000 UI/mL). At regular time-points, cultures were harvested for posterior analysis. Alkaline phosphatase (ALP) activity was determined on days 7 and 14, and cell growth was accessed by C3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell count on days 1, 3, 5, and 7. Flow cytometry analysis was used for investigating cell death on days 1, 3, 5, and 7. IFN-alpha affected ALP expression only at the higher concentration (1000 UI/mL) after 7 days (P < 0.05). No effects were detected in cell growth. In ribavirin treated cultures, concentrations higher than 2.5 microg/mL were associated with a decrease in ALP activity within 7 and 14 days (P < 0.01 and P < 0.001, respectively). Furthermore, the reduction in cell growth was dose-dependent and was detected after the fifth day. This decrease can be explained by an increase in the number of dead cells and a decrease in cell proliferation. In conclusion, our experiments demonstrated that ribavirin reduced, in a time- and dose-dependent manner, the number of metabolically active cells through a decrease in proliferation and an increase in cell death, and induced an impairment in osteoblast differentiation. These negative effects of ribavirin on osteblast-like cells might contribute to the bone loss reported in vivo.     

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.     

Two cases of hyperthyroidism induced by interferon-alpha therapy for renal cell carcinoma

Autoimmune thyroid disease is the result of a common side-effect of interferon-alpha (IFN-alpha) used to treat viral hepatitis C; but there have been few reports on thyroid disorders induced by IFN-a that was used to treat renal cell carcinoma. IFN-alpha therapy was conducted on two male patients, 75 and 44 years old, after radical nephrectomy. Six and five months, respectively, after this therapy, they complained of weight loss. Laboratory evaluation revealed hyperthyroidism; the thyroid stimulating hormone (TSH) level fell below normal; and the serum free T3 and T4 levels increased above normal values. Two months after the termination of IFN-alpha therapy, their thyroid hormone levels returned to normal without the help of antithyroid agents. In observational studies, thyroid dysfunction has been reported in 0.6 to 30% of the patients who had been treated with IFN-alpha. Careful observation is necessary to watch for the possible development of thyroid disorder during IFN-alpha therapy for renal cell carcinoma.     

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.     

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.     

De novo cryptogenic hepatitis after sustained eradication of hepatitis C following liver transplantation

Patients with recurrent hepatitis C (HCV) after liver transplantation (OLT) are often treated with interferon and ribavirin in an attempt to eradicate HCV and prevent cirrhosis. We report four patients who developed de novo cryptogenic hepatitis following sustained eradication of recurrent HCV, which led to decompensated liver disease in two patients, both of whom required listing for retransplantation. Between September 2000 and October 2001, 38 consecutive patients with recurrent HCV were treated with interferon alpha 2b and ribavirin, of whom eight patients (21%) developed a sustained response to HCV eradication. Four of these patients developed cryptogenic hepatitis, which led to decompensated cirrhosis in two patients. Both patients were listed for retransplantation but died on the waiting list. No etiology for liver disease was identified despite extensive investigations in all four patients including postmortem analysis in the two patients. We hypothesize that these individuals developed an aberrant immune response leading to allograft injury whose severity may be determined by underlying haplotype, degree of immunosuppression, presence/absence of HCV, and duration of treatment. We have not found any similar reports in the literature but anticipate more cases to be reported given the universal use of antiviral therapy for recurrent HCV.     

Preemptive therapy with pegylated interferon alpha-2b and ribavirin after liver transplantation for hepatitis C cirrhosis

We present our results of preemptive treatment with pegylated interferon and ribavirin after liver transplantation for hepatitis C cirrhosis. PATIENTS: Between September 2001 and August 2002, four patients were started on combination therapy with pegylated interferon-alpha-2b (1microg/kg weekly) and ribavirin (400-1000 mg/d) 3 to 4 weeks' posttransplant. Treatment was continued for 6 (genotype 3a, 2 patients) or 12 (genotype 1b, 2 patients) months. Virologic and biochemical responses as well as side effects were evaluated. RESULTS: Two patients (genotype 3a) became HCV (hepatitis C virus)-RNA negative after 3 months of therapy and are persistently negative 20 and 14 months after end of therapy. One patient (genotype 1b) became HCV-RNA negative 6 months after start of treatment, but therapy had to be withdrawn after 9 months owing to fatigue and suspicion of angina pectoris. One patient who was later retransplanted because of hepatic artery thrombosis discontinued therapy after 2.5 months owing to anemia, leukopenia, and no signs of HCV-RNA reduction. Interestingly, two of the responders were nonresponders prior to liver transplant. Median ALT levels at start of therapy were 98 U/L (r = 60-126) and 12 months later 40 U/L (r = 24-58) (n = 4). No rejection episode was detected. CONCLUSION: In patients liver-transplanted due to HCV-cirrhosis, combination therapy with pegylated interferon and ribavirin can be effective and safe in the early posttransplant period, thus preventing recurrent hepatitis C.     

Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation

BACKGROUND: Initial studies utilizing interferon-alpha and ribavirin for the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation showed promising results. Here we report our single-center experience using this combination therapy. METHODS: Liver transplant recipients with recurrent HCV (elevated serum aminotransferases, positive serum HCV RNA, and biopsy-proven hepatitis without rejection) received interferon-alpha (1.5-3 million units subcutaneously three times a week) and ribavirin (400-1000 mg p.o. daily) for 12 months or more. Serum aminotransferases, HCV RNA, and severity of hepatitis were followed. RESULTS: Thirty-two patients have been treated for at least 3 months, including 13 who have been on 12 or more months of therapy. Three died from allograft failure due to recurrent HCV. Dose reductions of interferon-alpha and/or ribavirin occurred in 22 patients. Thirteen had their medications permanently discontinued for severe adverse effects. Twenty-six patients (81%) had a biochemical response (BR; normalization of serum aminotransferases) after 3 months. End-of-treatment and sustained BR were 77% and 71%, respectively. Mean viral loads decreased 68-77%; however, only three patients became serum HCV RNA negative. After 12 months of therapy, no histological improvement was observed in 11 patients who were biopsied. Patients who received mycophenolate mofetil or daclizumab had a less likelihood of achieving a BR. CONCLUSIONS: A significant number of patients did not tolerate interferon-alpha or ribavirin. Although BR was excellent and mean viral loads decreased significantly, virological clearance was poor and no histological improvement was noted. A more efficacious treatment with less adverse effects for recurrent HCV after liver transplantation is needed.     

Successful treatment of fibrosing cholestatic hepatitis with pegylated interferon,ribavirin and sofosbuvir after a combined kidney–liver transplantation

Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti‐HCV therapy, that is pegylated‐interferon (peg‐interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg‐interferon, ribavirin, plus sofosbuvir to treat HCV‐induced FCH in a combined liver–kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir‐based anti‐HCV therapy can be successfully used to treat FCH after a liver or combined kidney–liver transplantation.