Predictive value of on-treatment response during full-dose antiviral therapy of patients with hepatitis C virus cirrhosis and portal hypertension.
OBJECTIVE
Therapy with full-dose pegylated interferon (PEG-IFN) and weight-based ribavirin has been evaluated in limited series of patients with hepatitis C virus (HCV) and advanced disease. In this study, we evaluated the efficacy and tolerability of full-dose antiviral therapy in patients with compensated, fully developed cirrhosis, and assessed the predictive value of on-treatment virological response.


METHODS
We studied 85 HCV-positive cirrhotic patients (82 Child-Pugh class A; 41 treatment-naïve) who were treated with PEG-IFN alpha-2(a) (1.5 microg kg(-1)week(-1)) or alpha-2(b) (180 microg week(-1)) and weight-based ribavirin for 24 (genotype 2-3) or 48 (genotype 1-4) weeks. Forty-three patients were genotype 1 (51%), and HCV-RNA was >600,000 IU mL(-1) in 53 patients (62%). Prevalence of portal hypertension and diabetes was 81% and 18% respectively.


RESULTS
Sustained virological response (SVR) was obtained in 22 patients (26%). Positive serum HCV-RNA at week 4 and week 12 of therapy predicted nonresponse (NR) in 85% (52/61) and 100% (38/38) of patients, respectively. Treatment was discontinued due to adverse events in 14 patients (16%). Genotype 1-4 (P = 0.02) and HCV-RNA >600,000 IU mL(-1) (P = 0.02) were the baseline parameters significantly associated with lack of SVR, whilst positive serum HCV-RNA at week 12 was the only parameter independently associated with NR (100% negative predictive value).


CONCLUSIONS
Full-dose antiviral therapy with PEG-IFN and ribavirin can be safely carried out even in patients with compensated, fully established cirrhosis and portal hypertension. Selecting patients on the basis of HCV genotype and viral load, and application of on-treatment stopping rule may help rationalize treatment in patients who are unlikely to obtain SVR.
Giannini
E G
EG
Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Basso
M
M
Savarino
V
V
Picciotto
A
A
D000998:Antiviral Agents / Q000627:therapeutic use*; D001835:Body Weight; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000821:virology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000235:genetics / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b