There is still a great deal of uncertainty surrounding the treatment of cirrhotic patients with combination therapy (particularly those with decompensated cirrhosis). It has generally been thought that the treatment was not advisable because the SVR rates at this stage of the disease tend to be significantly lower. This means there is a risk of the drugs accelerating the decompensation process. There can also be severe side effects for people with cirrhosis.
But recent studies have indicated that treatment may benefit some people with cirrhosis. These include people with compensated cirrhosis as well as some carefully selected patients with decompensated cirrhosis. For this second category the treatment is normally only offered to those who have not previously had treatment and who currently have few options other than liver transplantation.
Treatment may lead to SVR in nearly one third of patients and lead to reduction of inflammation and fibrosis. For those with decompensated cirrhosis awaiting a liver transplant, treatment may also be beneficial before undergoing the operation. If people can achieve SVR before the operation there is a reasonable chance that HCV will not return after the transplant. In those people in whom the virus is detectable the new liver is almost always re-infected after the transplant.
There are potential benefits of undergoing treatment for people with cirrhosis, and particularly decompensated cirrhosis. But at this stage of the disease they must be weighed against the frequency and severity of the side effects of peg-interferon/ribavirin.
The evidence is that treatment will only really benefit people with cirrhosis if they have not had treatment before or who have relapsed. Retreatment seems to be only marginal effective in non-responders.
A study in 2004 treated 48 people with bridging fibrosis or compensated cirrhosis with peg-interferon/ribavirin. All those on the trial had not previously undergone treatment. The results were relatively encouraging. Across the different treatment regimes in the trial SVR rates amongst genotype 1 were between 26%-37%.
For those with genotype 2 and 3 SVR rates ranged between 69%-75%. There were also improvements in fibrosis and inflammation suggesting that interferon-based therapies may delay disease progression. This could potentially reduce the rate of the liver’s decompensation and the need for liver transplantation
In a 2005 study conducted on 32 individuals with decompensated cirrhosis the authors concluded that antiviral therapy appears to be safe and effective in carefully selected patients, and that treatment may result in SVR in nearly one-third of patients.
Treatment consisted of pegylated interferon plus ribavirin (78.1% of patients), pegylated mono-therapy (12.5 % of patients) or interferon plus ribavirin (9.4%) for an average of 37.8 weeks. All of the patients were treated for complications of cirrhosis (predominantly ascites and varices) before starting treatment.
The overall SVR rate reported was 31.3% (genotype 1 21.1%, other genotypes - 53.8%). The ALT levels of 40% of people returned to normal. A total of 84.4% of patients in this study experienced some form of adverse event with six patients (18.8%) stopping treatment. Only one patient was required to discontinue therapy.
The most common side effects included anaemia, neutropenia, depression and infections. As the result of treatment, 5 patients (15.6%) in this study were removed from the transplant list due to improvements in liver function. No patient died as the result of therapy.
In another study 31 people with HCV infection and decompensated cirrhosis were treated with peg-interferon/ribavirin. Treatment was for 24 or 48 weeks, depending on genotype and early virologic response (EVR). 32% achieved sustained virologic response (SVR).
A reduction in dose to control toxicity was required in half of patients. Most of them also required peg-interferon dose reduction for neutropenia. Three people were forced to abandoned treatment due the severity of side effects.