Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.
OBJECTIVE
Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center.


METHODS
One hundred and twelve patients with histologically proven CHC were treated with Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al.


RESULTS
Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR.


CONCLUSIONS
This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.
Soresi
M
M
Cattedra di Medicina Interna e Cattedra di Medicina d'Urgenza, Dipartimento di Medicina, Clinica e delle Patologie Emergenti, Università di Palermo, Cattedra di Anatomia Patologia, Palermo, Italy.
Tripi
S
S
Franco
V
V
Giannitrapani
L
L
Alessandri
A
A
Rappa
F
F
Vuturo
O
O
Montalto
G
G
D000328:Adult; D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015992:Body Mass Index; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000150:complications* / Q000473:pathology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a