Treatment Response in Cirrhotic Hepatitis C Patients with Portal Hypertension
Patients with cirrhosis due to chronic hepatitis C virus (HCV) infection may
develop portal hypertension, a condition in which scarring in the liver
causes impaired blood flow and elevated intrahepatic blood pressure.
Due to the risk of complications, interferon-based therapy has traditionally
been considered contraindicated in cirrhotic patients, but some may benefit
from treatment.
At the 57th annual meeting of the American Association for Liver Diseases (AASLD)
last month in Boston, researchers from the University of Palermo in Italy
reported on a study to assess outcomes in a prospective cohort of HCV
positive patients with cirrhosis after antiviral therapy.
The study included 174 consecutive patients with Child-Pugh A5-A6 cirrhosis.
The mean age was 57 years, 62.1% were men, and 56.3% had esophageal varices.
Most (88.5%) had genotype 1 HCV. About two-thirds (67.2%) were
treatment-naive and 32.8% were previously treated with conventional
interferon monotherapy.
Participants were treated with pegylated interferon alone (27%) or pegylated
interferon plus ribavirin (73%), and were followed for at least 6 months
after therapy (median 24 months, range 6-53 months).
Results
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59 patients (34%) discontinued therapy due to
side effects, and 115 received the full scheduled treatment.
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32 out of 174 patients (18.3%) achieved
sustained virological response (SVR) in an intent-to-treat analysis, and 32
out of 115 (27.8%) in an as-treated analysis. |
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There were no significant differences in
treatment response among patients with and without esophageal varices (15.5
vs 21.1%; P = 0.3). |
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Patients with SVR: |
- were younger (53.7 vs 57.8 years; P < 0.01);
- were more likely to have genotype 2 or 3 HCV (65% vs 11.8%; P < 0.001);
- had higher baseline ALT levels (4.7 vs 3.6 x upper limit of normal [ULN];
P < 0.05);
- had lower baseline gamma-glutamyl transferase (GGT) levels (1.7 vs 2.7 x
ULN; P < 0.05).
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Logistic regression revealed that the following
were independent predictors of SVR:
- age 62 years or younger (RR 5.8; 95% CI 1.1-30.2);
- genotype 2 or 3 HCV (RR 18.1; 95% CI 5.1-64);
- baseline ALT > 3 ULN (RR 4.1; 95% CI 1.5-11.5);
- baseline GGT ? 1 ULN (RR 4.3;, 95% CI 1.6-11.6).
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During follow-up, 34 patients (19.5%) developed
at least 1 liver complication. |
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2 patients died due to liver-related causes,
and 1 died due to extrahepatic cancer. |
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All 34 patients with complications had genotype
1 HCV and 25 had esophageal varices. |
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31 liver-related events occurred in
non-responders, compared with 2 events in patients achieving SVR (22.5% vs
6.3%; P < 0.05). |
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By Cox regression analysis, esophageal varices
(RR 3.3; 95% CI 1.5-7.1) and SVR (RR 4.9; 95% CI 1.2-20.4) were
significantly associated with liver disease progression.
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Conclusion
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Pegylated interferon and ribavirin obtains a
sustained virological response in 1/5 of patients with compensated
cirrhosis," the researchers wrote in conclusion. "The sustained response was
more common for genotypes 2 or 3, in patients with age less than 60 years,
with elevated values of ALT, and low levels of GGT."
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Treatment withdrawal due to intolerance and
hematological toxicity was common, without life-threatening events," they
continued. "Patients with sustained virological response had a minor
incidence of disease complications during a short-term follow-up."
V Di Marco, P Almasio, S De Lisi, and others. The effect of
antiviral therapy on clinical outcome of HCV cirrhosis with portal
hypertension: a prospective cohort study. 57th AASLD. Boston, MA. October
27-31, 2006. Abstract 719.
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