NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances

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Abstract

<p class="first" id="d2579953e158">Chronic infection with hepatitis C virus (HCV) was previously the leading indication for liver transplant (LT) in the United States. However, since 2014 the use of direct-acting antivirals (DAAs) has decreased the chronic HCV burden, while the prevalence of nonalcoholic steatohepatitis (NASH) has risen substantially through the last decade. Both gender and ethnic disparities in indications for LT have been shown in the past but no data on this have been reported since the implementation of DAAs. </p>

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Most cited references 27

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Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Stefano Romeo, Julia Kozlitina, Chao Xing … (2008)

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.

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Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.

Silvia Sookoian, Carlos Pirola (2011)

Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations. We performed a systematic review by a meta-analysis; literature searches identified 16 studies. Our results showed that rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects; P < 1 × 10(-9) ), but also on the susceptibility of a more aggressive disease (GG homozygous had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater risk of developing fibrosis when compared with CC homozygous; P < 1 × 10(-9) ; data from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confidence interval [CI] 1.859-6.545, random model; P < 2 × 10(-4) ; data from 2,124 patients). Evaluation of the risk associated with heterozygosity for the variant suggests that the additive genetic model best explains the effect of rs738409 on the susceptibility to develop NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe histological features. Meta-regression showed a negative correlation between male sex and the effect of rs738409 on liver fat content (slope: -2.45 ± 1.04; P < 0.02). The rs738409 GG genotype versus the CC genotype was associated with a 28% increase in serum alanine aminotransferase levels. By summarizing the amount of evidence, this study provided unequivocal evidence of rs738409 as a strong modifier of the natural history of NAFLD in different populations around the world. Copyright © 2011 American Association for the Study of Liver Diseases.

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The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.

Miriam J Alter, Deanna Kruszon-Moran, Omana Nainan … (1999)

Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection.

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Journal

Title: The American Journal of Gastroenterology

Abbreviated Title: Am J Gastroenterol

Publisher: Springer Nature

ISSN (Print): 0002-9270

ISSN (Electronic): 1572-0241

Publication date (Electronic): June 8 2018

Article

DOI: 10.1038/s41395-018-0088-6

PubMed ID: 29880964

SO-VID: 932fb509-e341-4354-a4f5-3bc13b050cdd

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NASH Leading Cause of Liver Transplant in Women: Updated Analysis of Indications For Liver Transplant and Ethnic and Gender Variances

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Most cited references 27

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.

The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.

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