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Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C
- Source :
- Clinical Microbiology and Infection. 22(4):372-378
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- This study analysed the impact of PNPLA3 variants on liver histology of 168 HIV/hepatitis C virus (HCV)-coinfected patients who were naïve for HCV treatment. A athologist unaware of the patients' condition graded liver fibrosis and necroinflammation (Ishak) and steatosis (Kleiner). Patients were tested for PNPLA3 variants and genotyped for the PNPLA3 rs738409 C to G variant underlying the I148M substitution. All were hepatitis B surface antigen negative and stated no alcohol abuse. The mean age was 40.6 (37.6-44.1) years, 72.6% were males, 42% had HCV genotype 3, 38.9% HCV genotype 1 and 79.2% were receiving highly active antiretroviral therapy. The 79 patients with the PNPLA3 p.148I/M or M/M variants more frequently showed severe steatosis (score 3-4) than the 89 with PNPLA3 p.148I/I (43% vs. 24.7%, p 0.001), whereas no difference was observed in the degree of necroinflammation or fibrosis. Compared with 112 patients with lower scores, 56 with severe steatosis showed higher body mass index (p 0.03), higher rate of HCV genotype 3 (55.6% vs. 35.2%, p 0.01), PNPLA3 p.148I/M or M/M (60.7% vs. 39.3%, p 0.01) and lower CD4(+) cells/mm(3) (514.00 (390.5-673.0) vs. 500.00 (399.0-627.0); p 0.002). At multivariate analysis, body mass index (p 0.01), HCV genotype 3 (p 0.006), CD4(+) cell count (p 0.005) and PNPLA3 p.148I/M or M/M variants (p 0.01) were found to be independent predictors of severe liver steatosis. The PNPLA3 p.148 I/M or M/M variants and CD4(+) cell count were the only independent predictors of severe steatosis in patients with HCV non-3 genotypes. This is the first study to show that among HIV/HCV-coinfected patients the PNPLA3 p.148I/M or M/M variant have substantially less impact on steatosis for those with HCV genotype 3 than non-genotype 3.
- Subjects :
- Liver Cirrhosis
0301 basic medicine
Male
Necrosis
HIV Infections
medicine.disease_cause
Gastroenterology
0302 clinical medicine
Fibrosis
Genotype
HIV Infection
Membrane Protein
medicine.diagnostic_test
Histocytochemistry
Fatty liver
General Medicine
Liver biopsy
Necrosi
Infectious Diseases
Liver
Liver steatosi
030211 gastroenterology & hepatology
Female
medicine.symptom
Liver histology
Human
Adult
Microbiology (medical)
medicine.medical_specialty
Hepatitis C virus
Liver Cirrhosi
Polymorphism, Single Nucleotide
03 medical and health sciences
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
PNPLA3
business.industry
Membrane Proteins
Lipase
Hepatitis C, Chronic
medicine.disease
Virology
HIV/HCV coinfection
Fatty Liver
030104 developmental biology
Amino Acid Substitution
Steatosis
business
Body mass index
Subjects
Details
- ISSN :
- 1198743X
- Volume :
- 22
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Clinical Microbiology and Infection
- Accession number :
- edsair.doi.dedup.....25fe0fb8154a115e1c3f100d642c8cbb
- Full Text :
- https://doi.org/10.1016/j.cmi.2015.11.025