Sustained Response to Interferon-based Therapy Reduces Liver Complications and Mortality in HIV-HCV Coinfected Patients

HIV-HCV coinfected patients who achieve a sustained virological response (SVR) after hepatitis C treatment with pegylated or conventional interferon plus ribavirin had a lower risk for liver-related complications and death, according to a Spanish study published in the August 2009 issue of Hepatology.

By Liz Highleyman

Numerous studies have shown that chronic hepatitis C patients coinfected with HIV tend to experience more rapid liver disease progression, especially if they have a low CD4 cell count. As such, coinfected patients could potentially benefit more from hepatitis C treatment, but they typically do not respond as well as HCV monoinfected people to interferon-based therapy.

Juan Berenguer and colleagues with the GESIDA3603/5607 Study Group aimed to determine whether HCV clearance with treatment is associated with improved clinical outcomes in coinfected patients.

This partially prospective study included 711 consecutive HIV-HCV coinfected patients at 11 HIV clinics in Spain who started hepatitis C treatment using interferon-based therapy between 2000 and 2005. Of these, 44% received pegylated interferon alfa-2a (Pegasys) plus ribavirin, 38% received pegylated interferon alfa-2a (PegIntron) plus ribavirin, and 18% received the older conventional interferon plus ribavirin.

Most participants (72%) were men, the median age was 41 years, 21% had a prior AIDS-defining condition, the median baseline CD4 count was 544 cells/mm3, 84% were on combination antiretroviral therapy, and 52% had an undetectable HIV viral load. The median time since HCV infection was 18 years, 63% had HCV genotypes 1 or 4, 70% had HCV RNA > 500,000 IU/mL, and 39% had bridging fibrosis or cirrhosis.

The researchers determined SVR -- or continued undetectable HCV RNA at 24 weeks after the end of treatment -- and its association with clinical outcomes, defined as death (liver-related or non-liver-related), liver decompensation, hepatocellular carcinoma (HCC), and/or liver transplantation. The average follow-up period was about 21 months (range 12 to 39).

Results

	Of the 711 coinfected patients enrolled, 31% achieved SVR.
	During follow-up, the incidence rates of death and liver complications were significantly lower among patients who achieved SVR compared with those who did not (i.e., non-responders and relapsers): Overall mortality: 0.46 vs 3.12 per 100 person-years (PY) (P = 0.003); Liver-related mortality: 0.23 vs 1.65 per 100 PY (P = 0.028); Liver decompensation: 0.23 vs 4.33 per 100 PY (P <0.001).
	The rate of liver transplantation was 0.12 per 100 PY in the non-SVR group compared with none in the SVR group (P = 0.034).
	Similarly, the rate of hepatocellular carcinoma was 0.83 per 100 PY in the non-SVR group compared with no cases in the SVR group, but this did not reach statistical significance (P = 0.099).
	After adjusting for other relevant factors including degree of fibrosis, HCV genotype, HCV viral load, CDC clinical category, and nadir CD4 cell count, the adjusted hazard ratios (HRs) for liver-related events were: HR 8.92 for non-responders compared with responders (P = 0.032); HR 4.96 for patients with fibrosis grades F3-F4 (advanced to severe) versus those with grades F0-F2 (absent to moderate) (P < 0.001).

Based on these findings, the study authors wrote, "Our results suggest that the achievement of an SVR after interferon-ribavirin therapy in patients coinfected with HIV-HCV reduces liver-related complications and mortality."

"The results of our study, which is the largest to date to assess the natural history of hepatitis C after therapy with interferon and ribavirin, suggest that treatment and clearance of HCV can reduce the incidence of liver complications and death in patients coinfected with HIV-HCV," they elaborated in their discussion.

"Interestingly, these benefits could be shown in a relatively short follow-up time of approximately 20 months and were mainly due to a significant reduction in the rate of liver decompensation events (ascites, upper gastrointestinal bleeding, and hepatic encephalopathy) and in the rate of liver transplantation," they continued. "We could not demonstrate a reduction in the incidence of hepatocellular carcinoma."

In conclusion, they stated, "This highlights the importance of continued surveillance of these patients, particularly those with advanced fibrosis and cirrhosis."

Hospital Gregorio Marañón, Madrid, Spain; Hospital La Paz, Madrid, Spain; Hospital La Fe, Valencia, Spain; Hospital Donostia, San Sebastián, Spain; Hospital Ramón y Cajal, Madrid, Spain; Hospital Clinic, Barcelona, Spain; Hospital Príncipe de Asturias, Alcalá de Henares, Spain; Hospital Germans Trias i Pujol, Badalona, Spain.

8/18/09

Reference
J Berenguer, J Alvarez-Pellicer, P Miralles Martín, and others (GESIDA3603/5607 Study Group). Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 50(2): 407-413. August 2009. (Abstract).