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The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection.
PLoS One. 2015; 10(11):e0143429.Plos

Abstract

BACKGROUND

Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear.

METHODS

In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes.

RESULTS

75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes.

CONCLUSIONS

The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26599080

Citation

Scheiner, Bernhard, et al. "The Impact of PNPLA3 Rs738409 SNP On Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection." PloS One, vol. 10, no. 11, 2015, pp. e0143429.
Scheiner B, Mandorfer M, Schwabl P, et al. The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. PLoS ONE. 2015;10(11):e0143429.
Scheiner, B., Mandorfer, M., Schwabl, P., Payer, B. A., Bucsics, T., Bota, S., Aichelburg, M. C., Grabmeier-Pfistershammer, K., Stättermayer, A., Ferenci, P., Trauner, M., Peck-Radosavljevic, M., & Reiberger, T. (2015). The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. PloS One, 10(11), e0143429. https://doi.org/10.1371/journal.pone.0143429
Scheiner B, et al. The Impact of PNPLA3 Rs738409 SNP On Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. PLoS ONE. 2015;10(11):e0143429. PubMed PMID: 26599080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. AU - Scheiner,Bernhard, AU - Mandorfer,Mattias, AU - Schwabl,Philipp, AU - Payer,Berit Anna, AU - Bucsics,Theresa, AU - Bota,Simona, AU - Aichelburg,Maximilian C, AU - Grabmeier-Pfistershammer,Katharina, AU - Stättermayer,Albert, AU - Ferenci,Peter, AU - Trauner,Michael, AU - Peck-Radosavljevic,Markus, AU - Reiberger,Thomas, Y1 - 2015/11/23/ PY - 2015/05/22/received PY - 2015/11/04/accepted PY - 2015/11/25/entrez PY - 2015/11/26/pubmed PY - 2016/6/28/medline SP - e0143429 EP - e0143429 JF - PloS one JO - PLoS ONE VL - 10 IS - 11 N2 - BACKGROUND: Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear. METHODS: In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes. RESULTS: 75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes. CONCLUSIONS: The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26599080/The_Impact_of_PNPLA3_rs738409_SNP_on_Liver_Fibrosis_Progression_Portal_Hypertension_and_Hepatic_Steatosis_in_HIV/HCV_Coinfection_ L2 - http://dx.plos.org/10.1371/journal.pone.0143429 DB - PRIME DP - Unbound Medicine ER -