The association of IL28B genotype with the histological features of chronic hepatitis C is HCV genotype dependent.
The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.


METHODS
Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs.
86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs.
44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs.
72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4 (CC vs.
74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23-8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. roberta.dambrosio@unimi.it.
Roberta
R
D'Ambrosio
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. alessio.aghemo@policlinico.mi.it.
Alessio
A
Aghemo
INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy. defrancesco@ingm.org.
Raffaele
R
De Francesco
Division of Hepatology, Ospedale San Giuseppe IRCCS Multimedica, Università degli Studi di Milano, Milan 20100, Italy. mariagrazia.rumi@unimi.it.
Maria Grazia
MG
Rumi
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. enrico.galmozzi@gmail.com.
Enrico
E
Galmozzi
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. stella.denicola@gmail.com.
Stella
S
De Nicola
INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy. cheroni@ingm.org.
Cristina
C
Cheroni
Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA. drpjclark@gmail.com.
Paul J
PJ
Clark
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. guido.ronchi@libero.it.
Guido
G
Ronchi
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. pietro.lampertico@unimi.it.
Pietro
P
Lampertico
Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan 20100, Italy. massimo.colombo@unimi.it.
Massimo
M
Colombo
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005234:Fatty Liver / Q000150:complications; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000150:complications; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda