61da2d13e4cfa2e7aacb9c72927b36ac 280895.pdf 751bc37adf6d2e14b883c026bf73c5b78636f7da 280895.pdf 15cf03e9f4a8b55c240c5de250a7caeaa716ded1ef7a6d0f7e1b665d1c0ce12c 280895.pdf Title: Impact of a Loss-of-Function Variant in HSD17B13 on Hepatic Decompensation and Mortality in Cirrhotic Patients Subject: A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of progression to advanced fibrosis and cirrhosis. In this study, we aimed to evaluate the prognosis of cirrhotic patients harboring this variant. We performed a retrospective analysis on 483 prospectively recruited patients from four different hospitals in Spain, followed-up for at least 5 years. We collected clinical, demographic, and biochemical data, and we performed a genotyping analysis for common variants previously associated with liver disease risk (HSD17B13 rs72613567:TA and PNPLA3 rs738409). Patients homozygous for the TA allele showed a higher MELD score (p = 0.047), Child–Turcotte–Pugh score (p = 0.014), and INR levels (p = 0.046), as well as decreased albumin (p = 0.004) at baseline. After multivariate analysis, patients with the “protective” variant indeed had an increased risk of hepatic decompensation [aHR 2.37 (1.09–5.06); p = 0.029] and liver-related mortality [aHR 2.32 (1.20–4.46); p = 0.012]. Specifically, these patients had an increased risk of developing ascites (Log-R 11.6; p < 0.001), hepatic encephalopathy (Log-R 10.2; p < 0.01), and higher mortality (Log-R 14.1; p < 0.001) at 5 years of follow-up. Interactions with the etiology of the cirrhosis and with the variant rs738409 in PNPLA3 are also described. These findings suggest that the variant rs72613567:TA in HSD17B13 has no protective effect, but indeed increases the risk of decompensation and death in patients with advanced chronic liver disease. Keywords: cirrhosis; polymorphism; PNPLA3; HSD17B13; NAFLD; fibrosis; ascites; hepatic encephalopathy; SNP; hepatic decompensation Author: Antonio Gil-Gómez, Ángela Rojas, María R. García-Lozano, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Douglas Maya-Miles, Rocío Montero-Vallejo, Sheila Gato, Javier Gallego, Rubén Francés, Germán Soriano, Javier Ampuero and Manuel Romero-Gómez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Oct 6 08:26:49 2022 CEST ModDate: Thu Oct 6 08:29:53 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1299560 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- EXVEHZ+VnURWPalladioL Type 1 Custom yes yes no 10 0 ZTYPVJ+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 JIYDNL+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UJYSKM+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 ZPKPZB+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 FFAYKL+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 NJAOJC+CMSY10 Type 1 Builtin yes yes no 75 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 87 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 91 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 95 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 99 0 ArialMT TrueType WinAnsi no no no 107 0 BCDNEE+Arial-BoldItalicMT TrueType WinAnsi yes yes no 110 0 BCDOEE+宋体 TrueType WinAnsi yes yes no 114 0 Helvetica TrueType WinAnsi no no no 118 0 BCDLEE+Arial-BoldMT TrueType WinAnsi yes yes no 121 0 BCDMEE+Arial-ItalicMT TrueType WinAnsi yes yes no 125 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 137 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 141 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 145 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 149 0 ArialMT TrueType WinAnsi no no no 157 0 BCDOEE+宋体 TrueType WinAnsi yes yes no 160 0 BCDPEE+Arial-BoldMT CID TrueType Identity-H yes yes yes 164 0 BCDLEE+Arial-BoldMT TrueType WinAnsi yes yes no 172 0 BCDMEE+Arial-ItalicMT TrueType WinAnsi yes yes no 175 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 190 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 194 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 198 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 202 0 ArialMT TrueType WinAnsi no no no 210 0 BCDLEE+Arial-BoldMT TrueType WinAnsi yes yes no 213 0 BCDMEE+Arial-ItalicMT TrueType WinAnsi yes yes no 217 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-09 02:41:54 CEST RepresentationInformation: 280895.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-08 12:42:00 CEST Size: 1299560 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 360 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Baseline Characteristics and Genotyping Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Impact of rs72613567 Genotype on Mortality and Hepatic Decompensation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Effect of Etiology and Interactions with PNPLA3 Genotype Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Experimental Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: DNA Genotyping Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Info: Title: Impact of a Loss-of-Function Variant in HSD17B13 on Hepatic Decompensation and Mortality in Cirrhotic Patients Author: Antonio Gil-Gómez, Ángela Rojas, María R. García-Lozano, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Douglas Maya-Miles, Rocío Montero-Vallejo, Sheila Gato, Javier Gallego, Rubén Francés, Germán Soriano, Javier Ampuero and Manuel Romero-Gómez Subject: A common splice variant in HSD17B13 (rs72613567:TA) was recently found to be associated with a reduced risk of developing chronic liver disease in NAFLD patients and a reduced risk of progression to advanced fibrosis and cirrhosis. In this study, we aimed to evaluate the prognosis of cirrhotic patients harboring this variant. We performed a retrospective analysis on 483 prospectively recruited patients from four different hospitals in Spain, followed-up for at least 5 years. We collected clinical, demographic, and biochemical data, and we performed a genotyping analysis for common variants previously associated with liver disease risk (HSD17B13 rs72613567:TA and PNPLA3 rs738409). Patients homozygous for the TA allele showed a higher MELD score (p = 0.047), Child Turcotte Pugh score (p = 0.014), and INR levels (p = 0.046), as well as decreased albumin (p = 0.004) at baseline. After multivariate analysis, patients with the “protective” variant indeed had an increased risk of hepatic decompensation [aHR 2.37 (1.09 5.06); p = 0.029] and liver-related mortality [aHR 2.32 (1.20 4.46); p = 0.012]. Specifically, these patients had an increased risk of developing ascites (Log-R 11.6; p < 0.001), hepatic encephalopathy (Log-R 10.2; p < 0.01), and higher mortality (Log-R 14.1; p < 0.001) at 5 years of follow-up. Interactions with the etiology of the cirrhosis and with the variant rs738409 in PNPLA3 are also described. These findings suggest that the variant rs72613567:TA in HSD17B13 has no protective effect, but indeed increases the risk of decompensation and death in patients with advanced chronic liver disease. Keywords: cirrhosis; polymorphism; PNPLA3; HSD17B13; NAFLD; fibrosis; ascites; hepatic encephalopathy; SNP; hepatic decompensation Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Oct 06 08:26:49 CEST 2022 ModDate: Thu Oct 06 08:29:53 CEST 2022 ID: 0xd90d7996b024f5614588c488852b75d0, 0xd90d7996b024f5614588c488852b75d0 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: FFAYKL+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: FFAYKL+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JIYDNL+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: JIYDNL+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UJYSKM+URWPalladioL-Ital FontSubset: true FirstChar: 41 LastChar: 121 FontDescriptor: FontName: 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