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The impact of PNPLA 3 ( rs738409 C>G) polymorphisms on liver histology and long‐term clinical outcome in chronic hepatitis B patients
Author(s) -
Brouwer Willem P,
Meer Adriaan J,
Boonstra Andre,
Pas Suzan D,
Knegt Robert J,
Man Rob A,
Hansen Bettina E,
ten Kate Fiebo JW,
Janssen Harry LA
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12695
Subject(s) - medicine , gastroenterology , steatohepatitis , hepatocellular carcinoma , hazard ratio , overweight , interquartile range , fibrosis , hepatitis b , histology , liver biopsy , fatty liver , biopsy , obesity , confidence interval , disease
Background & Aims We aimed to assess the association between the patatin‐like phospholipase domain‐containing‐3 ( PNPLA 3 ) I148M polymorphism, liver histology and long‐term outcome in chronic hepatitis B ( CHB ) patients. Methods We enrolled 531 consecutive treatment naïve CHB patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all‐cause mortality and hepatocellular carcinoma ( HCC ) at long‐term follow‐up were obtained from national database registries. Results The prevalence of steatohepatitis increased with PNPLA 3 CC (14%), CG (20%) and GG (43%) ( P < 0.001). The association was altered by both gender ( P = 0.010) and overweight ( P = 0.015): the effect of PNPLA 3 on steatohepatitis was most pronounced among non‐overweight females (adjusted OR 13.4, 95% CI : 3.7–51.6, P < 0.001), and non‐overweight males (adjusted OR 2.4, 95% CI : 1.4–4.3, P = 0.002). Furthermore, PNPLA 3 GG genotype was associated with iron depositions ( OR 2.8, 95% CI : 1.2–6.4, P = 0.014) and lobular inflammation ( OR 2.2, 95% CI : 1.1–4.5, P = 0.032), but not with advanced fibrosis ( OR 1.1, 95% CI : 0.7–1.8, P = 0.566). The median follow‐up was 10.1 years (interquartile range 5.6 – 15.8), during which 13 patients developed HCC and 28 died. Steatohepatitis was associated with all‐cause mortality [Hazard ratio ( HR ) 3.1, 95% CI : 1.3–7.3, P = 0.006] and HCC ( HR 2.8, 95% CI : 0.9–9.2, P = 0.078), but no significant association was observed for PNPLA 3 . Conclusions In this cohort of biopsied CHB patients, PNPLA 3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC development or all‐cause mortality. The effect of PNPLA 3 on steatohepatitis was particularly pronounced among female patients without severe overweight.