Treatment of advanced infection
This section contains guidance on antiviral therapy for patients with cirrhosis and those referred for liver transplant. It also outlines the criteria for liver transplantation and gives recommendations for screening for hepatocellular carcinoma.
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Antiviral therapy
Patients with cirrhosis
Patients with cirrhosis are defined as having compensated or decompensated cirrhosis. Those with decompensation have deterioration with development of one or more of the following: jaundice, ascites, variceal bleeding or encephalopathy.
There are several large well conducted RCTs of interferon and ribavirin, pegylated IFN and ribavirin, and pegylated interferon monotherapy in patients with chronic HCV who have a high likelihood of progressing to endstage liver disease.122, 123, 172, 173 Subgroups within these trials had cirrhosis or advanced fibrosis. Randomisation distributed them evenly between the interventions so that subgroup analysis was possible. Therapy appeared no more toxic to the patients with cirrhosis compared to those without cirrhosis, but was less effective. The SVRs achieved were 50-70% for genotype 2 and 3, and 20-30% for genotype 1. 1+
No head-to-head trials of the different pegylated IFNs were identified. Long term therapy for patients with cirrhosis is under investigation but there are no results published to date.
Patients with compensated cirrhosis should be considered for therapy with pegylated IFN and ribavirin, unless contraindicated.
In patients with cirrhosis who obtain SVR with IFN treatments there is a significant reduction in the incidence of hepatocellular carcinoma compared to controls (number needed to treat = 5).174 In those who fail to obtain an SVR with IFN treatment there is still a significant reduction in incidence of HCC compared to controls.175 1++
Patients with compensated HCV cirrhosis may benefit from IFN treatment to reduce the risk of development of HCC. The duration of therapy required to achieve this is not clear.
There was insufficient evidence on the treatment of patients with HCV and decompensated cirrhosis to make a recommendation.
Patients refered for liver transplant
Several studies have addressed the benefits of antiviral therapy given in the period leading up to, or following, orthotopic liver transplantation (OLT).154, 176-179 In the period before transplantation many are excluded from therapy because of contraindications. SVR rates are low. There is little evidence for treatment in the peri-transplant period (the time period immediately pre-, during and post-transplantation). Post-transplant therapy is poorly tolerated, due to anaemia and leucopenia, but appears safe in regard to graft failure. In those patients able to tolerate full dose therapy, high SVRs are achieved. 3 1+
Patients in whom transplant is planned should not receive antiviral therapy in the pre-transplant or peri-transplant stages, except as part of clinical trials.
Patients should be considered for antiviral therapy post liver transplant to achieve HCV clearance in cases of recurrence of HCV related liver disease.
Liver transplantation
In early studies of patients transplanted for HCV cirrhosis, the five and 10 year survival rates were equivalent to patients post OLT for non-HCV causes (68% and 60%).179 In a more recent analysis of the United Network for Organ Sharing (UNOS) database outcomes were studied in HCV positive (5,640, 43%) and HCV negative recipients (7,386, 56.7%). In the HCV negative and the HCV positive recipient populations, five year patient survival rates were 83.5% vs. 74.6% (P<0.00001) and five year graft survival rates 80.6% vs. 69.9% (P<0.00001), respectively. HCV infection reduces outcome following transplantation but this effect is not sufficient to deny an individual patient transplantation.180 2+
Patients with HCV and transplantable hepatocellular carcinoma (one lesion < 5cm or fewer than three lesions < 3 cm, on cross-sectional imaging) have no decrease in survival benefit up to 48 months post orthotopic liver transplantation when compared to patients with HCV alone.179, 181 2+
Quality of life in patients post OLT for HCV is equivalent to patients with non-HCV at three years.182 3
Patients with hepatitis C virus and concurrent operable hepatocellular carcinoma should be offered liver transplantation.
Patients with HCV associated chronic liver failure should be offered liver transplantation.
No studies were found on the effectiveness of retransplantation in patients with graft loss due to HCV recurrence.
Screening for hepatocellular carcinoma
The results of studies evaluating the sensitivity and specificity of serum alpha fetoprotein for detection of HCC in individuals with HCV indicate that in isolation this marker is of limited value only.183 1+
Annual ultrasound scanning of patients with cirrhosis and HCV does not detect tumours at a stage that permits likely curative treatment.184 Scanning on a six monthly basis may result in the detection of tumours at a stage that permits curative therapy.185 2+
Methods of screening and surveillance other than alpha fetoprotein and ultrasound remain experimental.
The rate of development of HCC in patients with HCV who are non-cirrhotic is extremely low (7.6% vs 92.4%).186 2+
The measurement of alpha fetoprotein should not be used in isolation for screening or surveillance of the development of HCC in patients with hepatitis C.
Surveillance using ultrasound should take place at six monthly intervals.
Surveillance should be confined to patients with cirrhosis.
