Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates

Younossi, Zobair M.; Stepanova, Maria; Ong, Janus P.; Jacobson, Ira M.; Bugianesi, Elisabetta; Duseja, Ajay; Eguchi, Yuichiro; Wong, Vincent Wai‐Sun; Negro, Francesco; Yılmaz, Yusuf; Romero–Gómez, Manuel; George, Jacob; Ahmed, Aijaz; Wong, Robert J.; Younossi, Issah; Ziayee, Mariam; Afendy, Arian

doi:10.1016/j.cgh.2018.05.057

Cited by 628 publications

(530 citation statements)

References 31 publications

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“…Disease progression in NASH leads to the development of cirrhosis, resulting in various liver‐related outcomes, and is now one of the leading causes for liver transplantation . Other complications such as HCC may develop, with an annual incidence rate of 5.29 per 1,000 person‐years for NASH; and NAFLD is now a frequently observed cause of HCC among liver transplant wait‐listed patients in the United States . Retrospective long‐term follow‐up studies have observed significantly higher unadjusted cumulative probabilities of liver‐related events in patients with NASH …”

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Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

et al. 2019

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Background and Aims Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease are increasingly observed together in clinical practice, and development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver‐related morbidity and mortality. Our aims were to determine whether biopsy‐proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors. Approach and Results CHB patients attending two tertiary centers in North America and Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no‐NASH or probable/definite NASH based on standardized histological assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan‐Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events. There were 1,089 CHB patients, classified as no‐NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%) versus 27 (15%) experiencing outcome events during follow‐up, respectively. In the multivariable analysis adjusting for age, sex, hepatitis B e antigen serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (hazard ratio [95% confidence interval], 4.8 [2.6‐9.0], P < 0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (P = 0.01) or NASH alone (P < 0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (P < 0.05) in place of NASH. NASH was significantly associated with increased risk of hepatocellular carcinoma and death (P < 0.01) but not decompensation (P = 0.33). Conclusions In our large combined tertiary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver‐related outcomes or death compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.

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Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

et al. 2019

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“…The United States has had the highest prevalence of severe obesity for several decades . Consequently, it is not surprising that recent data have demonstrated that NASH is becoming an increasingly common indication for liver transplantation (LT) overall and is already the second most common indication for LT in patients with HCC in the United States . In contrast, the demand for LT for hepatitis C virus (HCV) has declined since 2015 following the introduction of safe and effective direct‐acting antivirals.…”

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Increasing Incidence of Nonalcoholic Steatohepatitis as an Indication for Liver Transplantation in Australia and New Zealand

et al. 2019

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The worldwide increase in obesity and diabetes has led to predictions that nonalcoholic steatohepatitis (NASH) will become the leading indication for orthotopic liver transplantation (OLT). Data supporting this prediction from outside the United States are limited. Thus, we aimed to determine trends in the frequency of NASH among adults listed and undergoing OLT in Australia and New Zealand (ANZ) from 1994 to 2017. Data from the ANZ Liver Transplant Registry were analyzed with patients listed for fulminant liver failure, retransplantation, or multivisceral transplants excluded. Nonparametric trend, Spearman rank correlation, and regression analysis were used to assess trends in etiologies of liver disease over time. Of 5016 patient wait‐list registrants, a total of 3470 received an OLT. The percentage of patients with NASH activated for OLT increased significantly from 2.0% in 2003 to 10.9% in 2017 (trend analyses; P < 0.001). In 2017, NASH was the third leading cause of chronic liver disease (CLD) among wait‐list registrants behind chronic hepatitis C virus (HCV; 29.5%) and alcohol (16.1%). Similarly, significant increases over time in the percentage of patients undergoing OLT were observed for HCV and NASH (all trend analyses; P < 0.001) but with significant reductions in primary sclerosing cholangitis and cryptogenic cirrhosis (both P < 0.05). By 2017, NASH was the third leading cause of liver disease among patients undergoing OLT (12.4%) and behind chronic HCV (30.2%) and alcohol (18.2%). NASH also became the third most frequent etiology of CLD in patients transplanted (13.8%) with concomitant hepatocellular carcinoma by 2017. In conclusion, NASH is increasing as a primary etiology of liver disease requiring listing and liver transplantation in ANZ.

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“…In addition to death and HCC, placement on the waitlist for liver transplantation is an important outcome. NASH has become the fastest‐growing and the second or third leading indication for liver transplantation in the United States …”

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confidence: 99%

Patient‐Reported Outcomes and the Economic Effects of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: The Value Proposition

Younossi¹

2018

Hepatology

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Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) can progress to cirrhosis, hepatocellular carcinoma (HCC), death, or liver transplantation. NASH has also been associated with impaired health-related quality of life and poses a significant economic burden. Due to the negative clinical and patient-reported outcomes and economic burden of NAFLD, it is necessary to review this disease through the lens of value-based care, in which value is proportional to clinical and quality outcomes and inversely proportional to the costs of delivering these outcomes. I review the components of outcomes measured for patients with NAFLD and NASH and relate them to the value proposition, with the aim to deliver optimal patient-centered care.

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Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates

Abstract: Nonalcoholic steatohepatitis is the most rapidly growing cause of HCC among US patients listed for liver transplantation.

Cited by 628 publications

References 31 publications

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

Nonalcoholic Steatohepatitis Is Associated With Liver‐Related Outcomes and All‐Cause Mortality in Chronic Hepatitis B

Increasing Incidence of Nonalcoholic Steatohepatitis as an Indication for Liver Transplantation in Australia and New Zealand

Patient‐Reported Outcomes and the Economic Effects of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: The Value Proposition

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