High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: Relationship with rejection episodes

Abstract

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 cyclosporinebased 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-RNApositive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporinebased 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). Cirrhosis related to chronic infection with the hepatitis C virus (HCV) has emerged as one of the leading indications for orthotopic liver transplantation (OLT) worldwide, accounting for 50% of transplantation in Spain.

Recurrent hepatitis C after liver transplantation: On-treatment prediction of response to peginterferon/ribavirin therapy

“…It has been estimated that as much as 8 to 44% of untreated patients develop cirrhosis within 5 to 7 years following LT. [1][2][3] Once cirrhosis occurs, the risk of hepatic decompensation and graft loss is high over a short period of time. 16 Furthermore, the results of retransplantation for recurrent HCV has been disappointing, with a 5-year survival rate of less than 50%.…”

“…Indeed, recurrent infection leads to cirrhosis in 10 to 25% of transplant recipients within 5 to 10 years, 1,2 and once cirrhosis occurs, the 1-year risk of hepatic decompensation reaches 40%. [1][2][3] Consequently, patient and graft outcome is significantly impaired in HCV-infected patients after LT compared to uninfected recipients. Post-LT outcome analysis of a large cohort of over 11,000 patients showed that HCV-positive transplant recipients have higher rates of mortality [hazard ratio: 1.23; 95% confidence interval (CI): 1.12-1.35] and allograft failure (hazard ratio: 1.30; 95% CI: 1.21-1.39) than do HCV-negative recipients.…”

Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation

“…1 Regretfully, recurrence of HCV infection is universal after LT, 2 and disease progression is significantly faster in immunosuppressed than in immunocompetent individuals. In liver transplant recipients, chronic HCV infection may lead to cirrhosis in as much as 30% of individuals only 5 years after LT. [3][4][5] Once liver cirrhosis is established, the cumulative probability of developing clinical decompensation is close to 50% 1 year after diagnosis and, more importantly, survival after decompensation is extremely short. 6 As a result of this accelerated course of HCV infection, longterm graft and patient survival are significantly reduced in patients undergoing LT for HCV-related cirrhosis compared with other groups.…”

Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation

“…1,2 HCV recurrence is apparent histologically in 40 to 60% of liver transplant recipients within the 1st postoperative year, 3,4 and may lead to cirrhosis of the graft in as many as 30% of the recipients within 4 to 5 years. 5,6 The clinical presentation of RHC is nonspecific and usually consists of elevated aminotransferases and vague symptoms. Histopathologic assessment is considered essential for the diagnosis and treatment of RHC; however, histologic features of recurrent hepatitis may be modified by immunosuppressive therapy, and can be difficult to differentiate from acute cellular rejection (ACR).…”