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Patatin-Like Phospholipase Domain-Containing 3 I148M Variant Is Associated with Liver Steatosis and Fat Distribution in Chronic Hepatitis B

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Abstract

Background

The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver steatosis and disease progression in nonalcoholic steatohepatitis and chronic hepatitis C.

Aims

The aim of the present study was to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical, histological, viral, and host parameters in Italian patients with chronic hepatitis B (CHB).

Methods

Ninety-nine patients with CHB entered the study and underwent a clinical, histological, virological, and biochemical evaluation. PNPLA3 (p.I148M) variants were genotyped.

Results

PNPLA3 rare variant (148M) was significantly associated with liver steatosis (p = 0.0019) and cholesterol (p = 0.04) levels, but not with fibrosis or histological activity index. The 13 patients with severe liver steatosis (score > 3) (38 %) were more frequently homozygous for PNPLA3 148M variant than the 86 without (6 %, p = 0.003). At logistic regression analysis, severe steatosis was independently associated with the rare allele (p = 0.001) and waist circumference, but not with body mass index (BMI).

Conclusions

In our CHB patients, the PNPLA3 polymorphisms influenced the development of liver steatosis, but not fibrosis status. The association of PNPLA3 p.I148M with liver steatosis increased with the greater amount of abdominal fat, irrespective of BMI.

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References

  1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–1231.

    Article  CAS  PubMed  Google Scholar 

  2. Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33:1358–1364.

    Article  CAS  PubMed  Google Scholar 

  3. Altlparmak E, Koklu S, Yalinkilic M, et al. Viral and host causes of fatty liver in chronic hepatitis B. World J Gastroenterol. 2005;11:3056–3059.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Gordon A, McLean CA, Pedersen JS, Bailey MJ, Roberts SK. Hepatic steatosis in chronic hepatitis B and C: predictors, distribution, and effect on fibrosis. J Hepatol. 2005;43:38–44.

    Article  CAS  PubMed  Google Scholar 

  5. Thomopoulos KC, Arvaniti V, Tsamantas AC, et al. Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis. Eur J Gastroenterol Hepatol. 2006;18:233–237.

    Article  PubMed  Google Scholar 

  6. Papatheodoridis GV, Chrysanthos N, Savvas S, et al. Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis. J Viral Hepat. 2006;13:303–310.

    Article  CAS  PubMed  Google Scholar 

  7. Tsochatzis E, Papatheodoridis GV, Manesis EK, Chrysanthos N, Kafiri G, Archimandritis AJ. Hepatic steatosis in chronic hepatitis B develops due to host metabolic factors: a comparative approach with genotype 1 chronic hepatitis C. Dig Liver Dis. 2007;39:936–942.

    Article  CAS  PubMed  Google Scholar 

  8. Bondini S, Kallman J, Wheeler A, et al. Impact of non-alcoholic fatty liver disease on chronic hepatitis B. Liver Int. 2007;27:607–611.

    Article  PubMed  Google Scholar 

  9. Yun JW, Cho YK, Park JH, et al. Hepatic steatosis and fibrosis in young men with treatment-naive chronic hepatitis B. Liver Int. 2009;29:878–883.

    Article  CAS  PubMed  Google Scholar 

  10. Peng D, Han Y, Ding H, Wei L. Hepatic steatosis in chronic hepatitis B patients is associated with metabolic factors more than viral factors. J Gastroenterol Hepatol. 2008;23:1082–1088.

    Article  CAS  PubMed  Google Scholar 

  11. Zheng RD, Xu CR, Jiang L, Dou AX, Zhou K, Lu LG. Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis. Int J Med Sci. 2010;7:272–277.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Kumar M, Choudhury A, Manglik N, et al. Insulin resistance in chronic hepatitis B virus infection. Am J Gastroenterol. 2009;104:76–82.

    Article  CAS  PubMed  Google Scholar 

  13. Petta S, Camma C, Di Marco V, et al. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int. 2011;31:507–515.

    Article  CAS  PubMed  Google Scholar 

  14. Wong VW, Wong GL, Chu WC, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56:533–540.

    Article  PubMed  Google Scholar 

  15. Park SH, Kim DJ, Lee HY. Insulin resistance is not associated with histologic severity in nondiabetic, noncirrhotic patients with chronic hepatitis B virus infection. Am J Gastroenterol. 2009;104:1135–1139.

    Article  CAS  PubMed  Google Scholar 

  16. Wong VW, Wong GL, Yu J, et al. Interaction of adipokines and hepatitis B virus on histological liver injury in the Chinese. Am J Gastroenterol. 2010;105:132–138.

    Article  CAS  PubMed  Google Scholar 

  17. Wong GL, Wong VW, Choi PC, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58:111–117.

    Article  PubMed  Google Scholar 

  18. Lesmana LA, Lesmana CR, Pakasi LS, Krisnuhoni E. Prevalence of hepatic steatosis in chronic hepatitis B patients and its association with disease severity. Acta Med Indones.. 2012;44:35–39.

    PubMed  Google Scholar 

  19. Kim KH, Shin HJ, Kim K, et al. Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPAR. Gastroenterology. 2007;132:1955–1967.

    Article  CAS  PubMed  Google Scholar 

  20. Na TY, Shin YK, Roh KJ, et al. Liver X receptor mediates hepatitis B virus X protein-induced lipogenesis in hepatitis B virus-associated hepatocellular carcinoma. Hepatology. 2009;49:1122–1131.

    Article  CAS  PubMed  Google Scholar 

  21. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology. 2010;52:904–912.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Valenti L, Rumi MG, Galmozzi E, et al. Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology. 2011;53:791–799.

    Article  CAS  PubMed  Google Scholar 

  24. Trepo E, Pradat P, Potthoff A, et al. Impact of patatin-like phospholipase-3 (rs738409 C > G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology. 2011;54:60–69.

    Article  CAS  PubMed  Google Scholar 

  25. Zampino R, Coppola N, Cirillo G, et al. Abdominal fat interacts with PNPLA3 I148M, but not with the APOC3 variant in the pathogenesis of liver steatosis in chronic hepatitis C. J Viral Hepat.. 2013;20:517–523.

    Article  CAS  PubMed  Google Scholar 

  26. Viganò M, Valenti L, Lampertico P, et al. Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B. Hepatology. 2013;58:1245–1252.

    Article  PubMed  Google Scholar 

  27. Brouwer WP, van der Meer AJ, Boonstra A, et al. The impact of PNPLA3 (rs738409 C > G) polymorphisms on liver histology and long-term clinical outcome in chronic hepatitis B patients. Liver Int.. 2014. doi:10.1111/liv.12695.

    PubMed  Google Scholar 

  28. Tong J, Guo J, Hu J, Hou S, Zhang Y, Li Q. Correlation between patatin-like phospholipase domain-containing protein 3 gene polymorphisms and liver cirrhosis in a Chinese Han population with chronic hepatitis B. Hepat Mon.. 2014;14:e18943. doi:10.5812/hepatmon.18943.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Coppola N, Zampino R, Sagnelli C, et al. Cannabinoid receptor 2-63 QQ variant is associated with persistently normal aminotransferase serum levels in chronic hepatitis C. PLoS ONE. 2014;9:e99450. doi:10.1371/journal.pone.0099450.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Expert Panel on the Identification, Evaluation, and treatment of overweight in adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Am J Clin Nutr. 1998;68:899–917.

    Google Scholar 

  31. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699.

    Article  CAS  PubMed  Google Scholar 

  32. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.

    Article  PubMed  Google Scholar 

  33. Coppola N, Marrone A, Pisaturo M, et al. Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection. Eur J Clin Microbiol Infect Dis. 2013;33:559–567.

    Article  PubMed  Google Scholar 

  34. Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol. 2011;26:1361–1367.

    PubMed  Google Scholar 

  35. Lin J, Wu JF, Zhang Q, Zhang HW, Cao GW. Virus-related liver cirrhosis: molecular basis and therapeutic options. World J Gastroenterol. 2014;20:6457–6469.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Zheng RD, Chen JN, Zhuang QY, Lu YH, Chen J, Chen BF. Clinical and virological characteristics of chronic hepatitis B patients with hepatic steatosis. Int J Med Sci.. 2013;10:641–646.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of interest

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Authors and Affiliations

  1. Internal Medicine and Hepatology, Second University of Naples, Via Pansini, 5-Edificio 3, 80131, Naples, Italy

    Rosa Zampino, Adriana Boemio, Aldo Marrone & Luigi Elio Adinolfi

  2. Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy

    Nicola Coppola, Nicolina Capoluongo, Margherita Macera & Evangelista Sagnelli

  3. Department of Pediatrics, Second University of Naples, Naples, Italy

    Grazia Cirillo, Anna Grandone & Emanuele Miraglia del Giudice

  4. Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy

    Maria Stanzione

Authors
  1. Rosa Zampino
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  2. Nicola Coppola
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  3. Grazia Cirillo
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  4. Adriana Boemio
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  11. Luigi Elio Adinolfi
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Correspondence to Rosa Zampino.

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Zampino, R., Coppola, N., Cirillo, G. et al. Patatin-Like Phospholipase Domain-Containing 3 I148M Variant Is Associated with Liver Steatosis and Fat Distribution in Chronic Hepatitis B. Dig Dis Sci 60, 3005–3010 (2015). https://doi.org/10.1007/s10620-015-3716-7

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  • DOI: https://doi.org/10.1007/s10620-015-3716-7

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