Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C

C. Sagnelli, M. Merli, Caterina Uberti Foppa, H. Hasson, G. Cirillo, A. Grandone, S. Salpietro, C. Minichini, E.M. Del Giudice, A. Lazzarin, E. Sagnelli, N. Coppola

Research output: Contribution to journalArticle

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/mm3 (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.
Original languageEnglish
Pages (from-to)372 - 378
Number of pages7
JournalClinical Microbiology and Infection
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Chronic Hepatitis C
Hepacivirus
HIV Infections
Histology
Liver
Genotype
CD4 Lymphocyte Count
Body Mass Index
HIV
Highly Active Antiretroviral Therapy
Fatty Liver
Hepatitis B Surface Antigens
Liver Cirrhosis
Alcoholism
Fibrosis
Multivariate Analysis

Keywords

  • HIV/HCV coinfection
  • Liver biopsy
  • Liver histology
  • Liver steatosis
  • PNPLA3

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C. / Sagnelli, C.; Merli, M.; Uberti Foppa, Caterina; Hasson, H.; Cirillo, G.; Grandone, A.; Salpietro, S.; Minichini, C.; Del Giudice, E.M.; Lazzarin, A.; Sagnelli, E.; Coppola, N.

In: Clinical Microbiology and Infection, Vol. 22, No. 4, 01.04.2016, p. 372 - 378.

Research output: Contribution to journalArticle

Sagnelli, C, Merli, M, Uberti Foppa, C, Hasson, H, Cirillo, G, Grandone, A, Salpietro, S, Minichini, C, Del Giudice, EM, Lazzarin, A, Sagnelli, E & Coppola, N 2016, 'Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C', Clinical Microbiology and Infection, vol. 22, no. 4, pp. 372 - 378. https://doi.org/10.1016/j.cmi.2015.11.025
Sagnelli, C. ; Merli, M. ; Uberti Foppa, Caterina ; Hasson, H. ; Cirillo, G. ; Grandone, A. ; Salpietro, S. ; Minichini, C. ; Del Giudice, E.M. ; Lazzarin, A. ; Sagnelli, E. ; Coppola, N. / Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C. In: Clinical Microbiology and Infection. 2016 ; Vol. 22, No. 4. pp. 372 - 378.
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N2 - 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/mm3 (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.

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