Sulkowski from Johns Hopkins University School of Medicine and
fellow investigators analyzed data from HIV/HCV coinfected patients
enrolled in the PARADIGM study to determine whether shifts in
Child-Pugh score predict liver decompensation.
decompensation occurs when the liver can no longer carry out
its normal functions, leading to symptoms such as ascites (abdominal
fluid accumulation), bleeding varices (varicose veins) in the
esophagus, and hepatic encephalopathy, or brain impairment due
to build-up of toxic substances.
The Child-Pugh score is calculated based on 2 clinical parameters
(ascites and encephalopathy) and 3 laboratory parameters, albumin
(a blood protein), total bilirubin (a pigment released when
old red blood cells are broken down), and international normalized
ratio (a measure of blood clotting ability based on prothrombin
PARADIGM included previously untreated HIV/HCV coinfected adults
with HCV genotype 1. Participants had a CD4 cell count of at
least 100 cells/mm3 and were either on stable antiretroviral
therapy (ART) or did not yet require HIV treatment. Individuals
with compensated liver cirrhosis (Child-Pugh score < 6) were
eligible for the study.
Participants were randomly assigned (1:2) to receive 180 mcg/week
pegylated interferon alfa-2a (Pegasys) for 48 weeks plus either
800 mg/day fixed-dose ribavirin or 1000-1200 mg/day weight-adjusted
ribavirin. Child-Pugh scores were assessed at 1 to 6 week intervals
during treatment and follow-up.
study entry, 46 participants had cirrhosis, all but 1 of
whom had baseline Child-Pugh scores available.
half of cirrhotic patients (22 out of 45) experienced shifts
in Child-Pugh score during treatment and follow-up.
such shifts were secondary to decreases in serum albumin
and/or increases in total bilirubin:
1 point shift in albumin only: 40% in 800 mg/day ribavirin
arm and 13% in 1000-1200 mg/day arm;
1 point shift in total bilirubin only: 7% and 17%,
1 point shift in albumin or total bilirubin: 60% and
was 1 episode of hepatic decompensation characterized by
bleeding esophageal varices in a patient with a baseline
Child-Pugh score of 5; this occurred 3 months after the
patient discontinued treatment due to insufficient response.
findings led the investigators to conclude, "During this
study, shifts in Child-Pugh score occurred in approximately
50% of coinfected patients with compensated cirrhosis but hepatic
decompensation was a rare event."
Explaining these results, they noted that shifts in Child-Pugh
score may be due to changes in albumin and bilirubin levels
that are not directly related to liver function. Decreased albumin
levels, for example, may result from treatment-related anorexia
(loss of appetite) and weight loss. Increased total bilirubin
may be caused by the protease inhibitor atazanavir
(Reyataz) or by hemolytic anemia due to ribavirin.
These results, they advised, "suggest that a shift in Child-Pugh
score is not a reliable predictor of hepatic decompensation
among coinfected cirrhotic patients treated with pegylated interferon
alfa-2a plus ribavirin."
Johns Hopkins University School of Medicine, Baltimore, MD;
Massachusetts General Hospital, Harvard Medical School, Boston,
MA; St. Michael's Medical Center, Newark, NJ; AIDS Healthcare
Foundation, Los Angeles, CA; Virginia Commonwealth University,
Richmond, VA; University of California San Diego, San Diego,
CA; Hospital São João, Porto, Portugal; Hospital
del Mar, Barcelona, Spain; Roche, Nutley, NJ; Fundacion de Investigacion
de Diego, Santurce, Puerto Rico; Ponce School of Medicine, Santurce,
M Sulkowski, RT Chung, J Slim, and others (PARADIGM Study Investigators).
Shifts in Child-Pugh score in patients coinfected with HIV-HCV
undergoing treatment with peginterferon alfa-2a (40kd) and ribavirin
are not predictive of hepatic decompensation. 45th Annual Meeting
of the European Association for the Study of the Liver (EASL
2010). Vienna, Austria. April 14-18, 2010. (Abstract).