Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (F10 ؋ 10 5 , 10-100 ؋ 10 5 , or G100 ؋ 10 5 Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived H3 months were reviewed. Mean follow-up was 669 ؎ 228 days for IFN patients and 594 ؎ 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P ‫؍‬ .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P ‫؍‬ .04, Cox proportional hazards model); HCV RNA level Ͼ100 ؋ 10 5 Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P ‫؍‬ .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P ‫؍‬ .05 at 1 month and P ‫؍‬ .003 at 3 months) but not in untreated patients (P ‫؍‬ .28 at 1 month and P ‫؍‬ .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P ‫؍‬ .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P F .02). One-and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P ‫؍‬ NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.(HEPATOLOGY 1998;28: 831-838.)Hepatitis C is becoming the most common indication for orthotopic liver transplantation. 1 After transplantation for this indication, however, hepatitis C viral RNA (HCV RNA) is detectable in serum in approximately 95% of patients. 2 Because the virus remains present, the new graft is at risk for recurrent disease. Clinical recurrence of hepatitis C has been reported in up to 62% of patients after orthotopic liver transplantation 2-4 and can lead to progressive liver failure, cirrhosis, and death. 5 Studies using quantitative assays for viral RNA have revealed a possible association between high serum HCV RNA levels and active hepatitis after transplantation. 6 The observation that quantitative HCV RNA levels are higher after liver and kidney transplantation than before suggests that immunosuppression may enhance...

Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.

Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 x 106 copies ml-1. The median HCV RNA concentration was 3.5 x 106 copies ml-1 and the cut-off for the upper 25th percentile (high titre) was 5 x 106 copies ml-1. Male patients had a median HCV RNA concentration of 3.9 x 106 copies ml-1, which was significantly higher than the median HCV RNA level for females (2.75 x 106 copies ml-1; P < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly (P < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African-American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders (P < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 (P < 0.001 for all comparisons).

We report a case of de novo hepatocellular carcinoma (HCC) in a patient with recurrent hepatitis C (HCV) and cirrhosis 7 years after orthotopic liver transplantation (OLT). This is a previously unreported observation in the natural history of posttransplantantion HCV infection and reiterates the strong oncogenic potential of HCV. Copyright 1999 by the American Association for the Study of Liver DiseasesA 63-year-old white man underwent OLT on July 6, 1990, for end-stage liver disease caused by chronic non A non B hepatitis and alcohol abuse. Ultrasonography before transplantation did not show a focal lesion. Serum alphafetoprotein level was 10.1 mg/mL (normal, 20 mg/mL). The donor was a 65-year-old woman in whom the HCV status was not determined at the time of organ donation. The preperfusion and postperfusion liver biopsy specimens obtained around the time of transplantation showed lipofuscinosis, a finding consistent with the age of the donor, but there was no evidence of hepatitis. The explanted liver, sectioned every 0.5 cm, showed micronodular cirrhosis, moderate lymphocytic septal inflammation, mild piecemeal necrosis, and areas of multiacinar collapse. There was no malignancy. The patient was started on cyclosporine, 125 mg twice daily; azathioprine, 100 mg four times daily; and prednisone, 20 mg four times daily. Six months later, he had biopsy-proven hepatitis and positive HCV RNA in the serum detected by reverse-transcriptase polymerase chain reaction. Over the next 6 months, the hepatitis progressed to stage III, in transition to cirrhosis. The azathioprine dose was reduced to 75 mg four times daily 12 months after OLT and to 50 mg four times daily at 18 months. Two years after OLT, the prednisone dose was reduced to 5 mg four times daily. Three and one half years later, he was maintained on cyclosporine, 75 mg twice daily, and prednisone, 5 mg four times daily every other day, with no evidence of rejection. Blood cyclosporine levels were maintained at 150 to 200 mg/mL. He remained clinically stable for the next 6 years, when he underwent a second OLT for a decompensated liver. Ultrasonography before transplantation showed cirrhosis with a 1.4-cm solid hypoechoeic mass. Serum alphafetoprotein level was 73.6 mg/ mL.The explanted liver showed chronic hepatitis and cirrhosis, with a well-demarcated, hemorrhagic, and focally necrotic 1.5-cm nodule in the right lobe. Microscopically, this was a welldifferentiated HCC arising in a macroregenerative nodule. Fluorescent in situ hybridization for X and Y chromosomes showed the tumor to be XX, confirming its de novo origin in the engrafted liver. The patient died of sepsis 75 days after the surgery.