Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(+) group was significantly higher than in the HCV(−) group (37% vs. 22%, P < .001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P = .0001). Although survival has increased in the HCV(−) group in recent years, it has significantly decreased in HCV recipients (P < .0001). The main cause of death among the latter was decompensated graft cirrhosis (n = 23/105, 22%), whereas that of HCV(−) patients was infections (n = 10/52, 19%). Reasons for the recent worse outcome in HCV(+) recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV(+) recipients than among HCV(−) ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.

The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver biopsies, and (2) to determine predictors for clinical decompensation, retransplantation, and mortality rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically compensated at histologic diagnosis of cirrhosis (post-liver transplantation cirrhosis) were included and followed up for 1 year (15 days-3.5 years). All patients tested were infected with genotype 1b. Predictive variables included histologic activity index (HAI) at post-liver transplantation cirrhosis, liver function tests, age, sex, and maintenance immunosuppression. Eighteen of 39 patients developed at least 1 episode of decompensation after a median of 7.8 months (4 days-2.6 years; 93% ascites). The cumulative probability of decompensation was 8%, 17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and 12 months, respectively. Patient survival rates dropped significantly once decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months, respectively). Variables associated with decompensation, retransplantation, and mortality rate included a high Child-Pugh score (>A), low levels of albumin at post-liver transplantation cirrhosis, and a short interval between liver transplantation and post-liver transplantation cirrhosis. The natural history of clinically compensated HCV-graft cirrhosis is shortened when compared with immunocompetent patients. If retransplantation is considered, it should be performed promptly once decompensation develops.

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine–based HCV–infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV–related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first–year liver biopsy findings. We studied 81 consecutive HCV–RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow–up of 1 year. All patients received cyclosporine–based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow–up was 32 months (range, 12–60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV–related cirrhosis at a median time of 24 months (range, 12–48 months), with an actuarial rate of HCV–cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P = .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P = .001). The degree of activity and fibrosis score in the first–year biopsy were higher in patients who developed cirrhosis than in those who did not (P = .008 and .18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First–year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.

Pegylated interferon (pegIFN) and ribavirin eradicates hepatitis C virus (HCV) in one third of liver recipients with recurrent disease. Side effects are frequent and potentially life threatening. Our aim was to define the long-term benefits of antiviral therapy in recurrent HCV. Eighty-nine (89) recipients (genotype 1: 86.5%) were treated with IFN (n = 31) or pegIFN (n = 58) plus ribavirin and 75 untreated contemporaneous disease-matched controls. The major end point was survival from transplantation. Survival, progression to cirrhosis and clinical decompensation since start of therapy were compared between sustained virologic responders (SVRs) and nonresponders (NRs). Results revealed 44 patients died during the follow-up (20% treated vs. 35% controls; p = 0.05). Patient survival was higher in treated compared to controls (7 years: 74% vs. 62%; p = 0.04). Among treated patients, an SVR was achieved in 37% (IFN 16% vs. peg-IFN 48%; p = 0.03). About 2/33 SVRs and 16/56 NRs died (p = 0.01) due to HCV-disease (56%), IFN-induced rejection (11%), both causes (11%) or others (22%). Five-year survival was greater in SVRs than in NRs (93% vs. 69%, p = 0.032). In patients without baseline cirrhosis, progression to cirrhosis occurred more frequently in NRs (27/42 vs. 6/16; p = 0.06). The 5-year risk of graft decompensation was higher in NRs (33% vs. 16%; p = 0.04). Antiviral therapy is associated with improved long-term outcome in recurrent HCV.