By Liz Highleyman

Treatment with pegylated interferon plus ribavirin can cause difficult side effects and cures only about half of people with chronic hepatitis C. Furthermore, HCV leads to advanced liver disease such as cirrhosis (replacement of functional liver cells with scar tissue) or hepatocellular carcinoma (a type of liver cancer) in only a minority of patients. Therefore, clinicians attempt to wait long enough to be sure an individual is progressing and truly needs treatment, while not waiting too long, since interferon does not work as well and side effects can be worse in people with severe disease.

Experts have debated the best time to start treatment for people with advanced liver disease. Interferon and ribavirin are more likely to cause adverse events in people with cirrhosis, but these are also the patients who stand to benefit most if successful therapy can halt or slow disease progression.

Compensated cirrhosis means the liver is heavily scarred but can still carry out most if its vital functions. Decompensated cirrhosis means the liver is no longer working properly to filter blood, leading to conditions such as portal hypertension, bleeding varicose veins in the esophagus, ascites (abdominal fluid build-up), and hepatic encephalopathy (neurocognitive impairment).

Sammy Saab and colleagues sought to determine the most cost-effective timing for pegylated interferon plus ribavirin treatment (48 weeks) in patients with advanced liver disease related to genotype 1 HCV infection -- the most difficult type to treat.

The study included about 4000 participants followed over 17 years. The investigators used a Markov mathematical model to compare treatment 4 treatment strategies, with approximately equal numbers of patients in each group:

1	No treatment;
2	Antiviral therapy for patients with compensated cirrhosis;
3	Antiviral therapy for patients with decompensated cirrhosis;
4	Antiviral therapy for patients with progressive fibrosis due to recurrent HCV post-transplantation.

They looked at outcomes including total cost per patient, number of quality-adjusted life years (QALYs) saved, cost per QALY saved, number of deaths, number of cases of hepatocellular carcinoma, and number of liver transplants required.

Results

	All 3 treatment strategies were cost-saving compared with no therapy, but treating patients with compensated cirrhosis was much more cost-effective and greatly improved survival:
	Treatment during compensated cirrhosis: increased QALYs by 0.950 and saved $55,314 compared with no treatment. Treatment during decompensated cirrhosis: increased QALYs by 0.044 and saved $5511. Treatment during HCV recurrence after transplantation: increased QALYs by 0.061 and saved $3223.
	Compared with no treatment, antiviral therapy for patients with compensated cirrhosis resulted in:
	119 fewer deaths; 54 fewer cases of hepatocellular carcinoma; 66 fewer liver transplants.

In conclusion, the study authors wrote, "the treatment of patients with compensated cirrhosis was found to be the most cost-effective strategy and resulted in improved survival and decreased cost in comparison with all other strategies."

"This study provides pharmacoeconomic evidence in support of treating HCV in patients with compensated cirrhosis before progression to more advanced liver disease," they added.

In an accompanying editorial, hepatology experts Angel Rubin and Marina Berenguer from Valencia, Spain, offered the caveat that models such as this do not take into account all the many variables that can affect disease progression and treatment response, recommending that "Physicians must decide whether the most cost-effective approach is the most appropriate one in each individual."

Investigator affiliations: Departments of Medicine, University of California at Los Angeles, Los Angeles, CA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA; Harbor-UCLA Medical Center, Torrance, CA; Huntington Medical Research Institutes, Pasadena, CA.

7/2/10

References

S Saab, DR Hunt, MA Stone, and others. Timing of hepatitis C antiviral therapy in patients with advanced liver disease: a decision analysis model. Liver Transplantation 16(6): 748-759 (Abstract). June 2010.

A Rubin and M Berenguer. An economic analysis of antiviral therapy in patients with advanced hepatitis C virus disease: still not there! (Editorial). Liver Transplantation 16(6): 697-700. June 2010.

Other source

Wiley-Blackwell. Antiviral therapy during compensated cirrhosis most cost-effective approach. Media advisory. May 27, 2010.