Sustained Virological Response to Interferon-based Therapy Slows Progression of Liver Cirrhosis in Hepatitis C Patients

		SUMMARY: Sustained response to interferon-based treatment for chronic hepatitis C virus (HCV) infection can slow the rate of progression to hepatic decompensation, liver cancer, and liver-related death, according to 2 studies presented this month at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009) in Boston.

By Liz Highleyman

V. Di Marco and colleagues from Italy (abstract 345) assessed whether antiviral therapy that leads to clearance of HCV RNA at an advanced stage of disease improves long-term outcomes for patients with cirrhosis (scarring) of the liver.

Compensated cirrhosis means the liver is badly damaged, but can still carry out most of its essential functions; decompensated disease occurs when the liver can no longer do so. As liver disease progresses, accumulating scar tissue impedes the flow of blood through the organ, resulting in symptoms such as portal hypertension, abdominal fluid accumulation (ascites), and enlarged, weakened blood vessels (varices) in the esophagus and stomach.

The investigators followed a prospective cohort of 358 patients with compensated HCV-related cirrhosis, with or without esophageal varices. Study participants were treated with pegylated interferon alfa-2b (PegIntron), at does of 1 or 1.5 mg/kg/week, plus 1000-1200 mg/day weight-adjusted ribavirin.

Participants were enrolled starting in 2001. All had more than 24 months of follow-up, allowing evaluation of sustained virological response (SVR), or continued undetectable HCV viral load 6 months after completion of treatment. Participants underwent ultrasound prior to therapy and every 6 months to assess presence of esophageal varices.

Results

	Overall, 79 patients (22%) achieved SVR.
	During a median 40 months of follow-up, 3 patients who achieved SVR developed decompensation, compared with 76 non-sustained-responders.
	1 patient with SVR and 78 without SVR developed hepatocellular carcinoma (HCC).
	In a multivariate analysis, the following factors were independently associated to hepatic decompensation:
	Lack of SVR: odd ratio (OR) 4.36, or more than 4 times higher risk; Presence of esophageal varices: OR 3.73; Child Pugh score of 6: OR 2.79; Platelet count below 90,000 cells/mm3: OR 1.94.
	The following factors were independently associated with development of HCC:
	Lack of SVR: OR 10.10, or more than 10 times higher risk; Platelet count below 90,000 cells/mm3: OR 2.97; Male sex: OR 2.90.
	Liver-related mortality was independently associated with:
	Lack of SVR: OR 8.59; Platelet count below 90,000 cells/mm3: OR 2.85.

Based on these findings, the investigators concluded, "SVR after antiviral treatment obtains a meaningful reduction in the rate of hepatic decompensation, of HCC, and of liver-related deaths in patients with compensated HCV cirrhosis, regardless of the presence of portal hypertension at the time of starting treatment."

Esophageal Varices

In a related study, S. Bruno and colleagues (abstract 281), also from Italy, conducted a study to assess the cumulative incidence and predictors associated with development of esophageal varices and to evaluate the impact of antiviral therapy and emergence of HCC on varice occurrence.

The researchers studied 218 consecutive patients with compensated HCV-related cirrhosis but free of esophageal varices when they enrolled between 1989 and 1992. During a median follow-up period of 11.4 years, 149 participants received interferon-based antiviral therapy. Ultrasound and upper endoscopy were performed at intervals of 6 months and 3 years intervals, respectively.

Results

	34 treated patients (23%) achieved SVR, and none of them developed esophageal varices.
	Of the 184 patients who were either not treated or did not achieve SVR, 67 developed esophageal varices.
	In a multivariate analysis, development of esophageal varices was significantly associated with:
	HCV genotype 1b: hazard ratio (HR) OR 2.40; Elevated baseline MELD score: HR 1.20 per 1-point increase.
	51 of the untreated or non-responder patients who were free of varices at the last endoscopy developed HCC.
	The 10 year cumulative incidence of esophageal varice detection were as follows:
	17% among patients without HCC; 67% among all patients who developed HCC; 64% among patients who developed HCC without previous or concurrent decompensation.
	After adjustment for other confounding factors, having HCC was associated with an approximately 3-fold increased risk of esophageal varice development (HR 2.87).

"SVR achievement prevents esophageal varice development in the long-term," the researchers concluded. "In addition to genotype 1b and MELD score at baseline, HCC occurrence is the main determinant associated with esophageal varice emergence. As a result, the current guidelines for esophageal varice surveillance should be revised accordingly."

11/24/09

References

V Di Marco, V Calvaruso, S De Lisi, and others. HCV clearance after PEG IFN plus RBV improves the course of HCV cirrhosis regardless of portal hypertension. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 345.

S Bruno, A Crosignani, C Facciotto, and others. The impact of sustained virologic response and hepatocellular carcinoma occurrence on the de-novo development of esophageal varices in compensated, HCV-induced cirrhosis. A long term prospective study. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 281.