Timing and Severity of Initial Hepatitis C Recurrence as Predictors of Long-Term Liver Allograft Injury1

321

191

Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNApositive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 ؋ 10 6 U/d; (2) group B, interferon alfa-2b, 3 ؋ 10 6 U three times weekly; or (3) group C, interferon alfa-2b, 1 ؋ 10 6 U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis. C hronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. 1 Although patients undergoing liver transplantation for HCV have been reported to have similar overall patient and graft survival to most other indications, 2-6 recurrence of HCV is a substantial source of morbidity, mortality, and graft loss. 2,4,7-10 To date, meaningful data regarding posttransplantation follow-up in HCV-infected recipients are only available for a mean of 3 to 5 years. [2][3][4][5][6] In the nontransplantation setting, it is estimated that the mean time from infection to the development of cirrhosis is 20 years. 11,12 In liver transplant recipients, the course of HCV-induced liver injury is accelerated, with HCV recurrence apparent histologically in approximately 50% of HCVinfected transplant recipients and HCV-associated allograft failure leading to death or graft loss in approximately 10% of transplant recipients by the fifth postoperative year. 2,3,7,10,[13][14][15][16][17] Greater pretransplantation levels of viremia have been associated with attenuated patient and allograft survival among HCV-infected liver transplant recipients. 7 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplant Database report...

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confidence: 99%

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Crippin

McCashland

Terrault

et al. 2002

321

191

“…[1][2][3][4] Recent data suggest that in approximately 20% of HCV-related transplantations, allograft cirrhosis develops within 5 years. [5][6][7][8][9] HCV-related re-OLT increased significantly throughout the early 1990s, 10 but there are no recent prevalence data to show if this trend continues.…”

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confidence: 99%

Poor survival after liver retransplantation: Is hepatitis C to blame?

Watt

Lyden

McCashland

2003

Data from 1990 to 1996 suggest that the prevalence of hepatitis C virus (HCV) infection in repeated orthotopic liver transplantation (re-OLT) is increasing, and patient survival may be worse. Aims of the study are to: (1) assess the prevalence of HCV in re-OLT, (2) compare survival between primary OLT and re-OLT for HCV versus non-HCV diseases, and (3) evaluate Model for End-Stage Liver Disease (MELD) scores in re-OLT. The United Network for Organ Sharing database for adult patients undergoing primary OLT or re-OLT from January 1996 to June 2002 was analyzed. Patients with malignancy or those who underwent re-OLT within 30 days of primary OLT were excluded. A total of 22,120 primary OLTs and 2,129 reOLTs were performed. HCV was noted in 9,564 primary OLTs (43.2%) and 899 re-OLTs (42.2%). Overall 1, 3, and 5-year patient survival rates were 86%, 79%, and 73% for primary OLT, but 67%, 56%, and 52% for re-OLT (P < .001). Survival rates of patients with HCV at 1, 3, and 5 years were 86%, 76%, and 68% for primary OLT and 61%, 50%, and 45% for re-OLT (P < .001). Survival was less for patients with HCV compared with those with autoimmune hepatitis (AIH) and hepatitis B for re-OLT (P < .01). However, survival after re-OLT was no different for those with HCV than for those with all other causes. MELD scores between 11 and 20 were the most common for re-OLT. A marked decreased in survival was noted in all patients who underwent re-OLT with MELD scores greater than 25. HCV prevalence in OLT has reached a plateau in recent years. Survival after re-OLT is inferior to that for primary OLT, but re-OLT survival appears to have improved. Survival after re-OLT is lower in patients with HCV compared with those with AIH and hepatitis B, but no different than for those with most other liver diseases. Survival appeared worse in patients who underwent re-OLT with a MELD score greater than 25. (Liver Transpl 2003;9:1019-1024.) R ecurrence of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) is almost universal. [1][2][3][4] Recent data suggest that in approximately 20% of HCV-related transplantations, allograft cirrhosis develops within 5 years. 5-9 HCV-related re-OLT increased significantly throughout the early 1990s, 10 but there are no recent prevalence data to show if this trend continues.Patient survival after primary OLT for HCV infection throughout the 1990s was similar to that for most other indications for OLT. [11][12][13] However, a recent study by Forman et al 14 showed an increased rate of death and allograft failure in HCV-positive compared with HCV-negative transplant recipients. 14 In general, re-OLT has a lower survival rate than primary OLT. [15][16][17] In small studies, patient survival after re-OLT for HCV was not different compared with re-OLT for other causes. 1,3,12,18 Conversely, several other studies suggested that survival after re-OLT for HCV is significantly worse than that for non-HCV-related indications. 10,[19][20][21] These studies also suggested that survival is worse in patients wit...

“…These include high pretransplant viral load, the occurrence of acute rejection episodes requiring bolus corticosteroids or antilymphocyte therapy, the presence of HCV genotype 1a of 1b, HCV patients who have received organs from older donors, and the development of cytomegalovirus infection posttransplantation. [32][33][34][35][36][37] In addition, one study has suggested that early recurrence and the severity of recurrence are both associated with a poor prognosis. 33 Recurrent hepatitis C can present as an acute hepatitis or, more commonly, has an insidious onset of abnormal liver tests in which portal hepatitis and/or fibrosis are shown on liver biopsy.…”

Section: S65mentioning

confidence: 99%

Late hepatic allograft dysfunction

Wiesner

2001

Key Points1. Lifelong monitoring of graft function, immunosuppressive levels, and screening for drug toxicity is required in all liver recipients.2. Late hepatic allograft dysfunction is common and is caused by a variety of etiologies including rejection, infection, biliary/vascular abnormalities, recurrence of disease, and drug hepatotoxicity.3. In all patients with late hepatic allograft dysfunction, liver biopsy should be performed to assess for the presence of rejection, and to thus avoid excessive use of bolus corticosteroid therapy and guide appropriate immunosuppressive management.4. Recurrence of disease is the most common cause of late hepatic allograft dysfunction.5. Hepatitis C universally reinfects the hepatic allograft, and is associated with decreased patient and graft survival and leads to the recurrence of cirrhosis in 28% of patients within 5 years of transplantation.