Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data

Kabbany, Mohammad Nasser; Selvakumar, Praveen Kumar Conjeevaram; Watt, Kymberly D.; López, Rocío; Akras, Zade; Zein, Nizar N.; Carey, William D.; Alkhouri, Naim

doi:10.1038/ajg.2017.5

Cited by 204 publications

(144 citation statements)

References 24 publications

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“…NASH with fibrosis) may reach up to more than 4 million of adult Americans. Of note, a recent study suggest that the prevalence of NASH-related cirrhosis and fibrotic NAFLD has increased 2.5-fold and 2-fold respectively in the U.S., which is in line with the observation that NASH-related cirrhosis is surpassing hepatitis C virus-related cirrhosis as the top etiology for adults listed for liver transplantation in that country (9). Thus, NASH-related cirrhosis is rising as a medical problem and, given the lack of awareness of NAFLD, it is likely that the real disease burden of this condition remains occult.…”

supporting

confidence: 73%

NASH‐related cirrhosis: An occult liver disease burden

Arrese

Feldstein

2017

Hepatology Communications

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supporting

confidence: 73%

NASH‐related cirrhosis: An occult liver disease burden

Arrese

Feldstein

2017

Hepatology Communications

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“…Recent data demonstrated that approximately 4.5 million people might have advanced fibrosis related to NASH in the United States. (10) Unfortunately, studies by our group and others have clearly shown that most patients with end-stage liver disease secondary to NASH had no previous diagnosis of liver disease. (11,12) This is related to the lack of clear guidance on whom to screen for NASH and how to do it in high-risk individuals.…”

Section: Challenge #1: Most Patients With Nash-associated Advanced Fimentioning

confidence: 84%

Looking Into the Crystal Ball: Predicting the Future Challenges of Fibrotic NASH Treatment

2019

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Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide, and its aggressive form of nonalcoholic steatohepatitis (NASH) is becoming a leading cause for end‐stage liver disease and liver transplantation in the United States. In patients with NASH, the presence of advanced fibrosis is considered the most important prognostic factor in predicting liver‐related morbidity and mortality. Unfortunately, there are no US Food and Drug Administration (FDA)–approved medications to treat patients with NASH‐induced advanced fibrosis. However, the field of drug development to treat NASH and fibrosis has witnessed major advances over the past 5 years with several medications in phase III trials. Results from some of these trials are expected in 2019 with potential FDA approval in 2020. Clinicians who treat patients with NAFLD are likely to face several challenges over the next few years related to identifying patients with advanced fibrosis who may derive most benefit from pharmacologic treatment, the requirement for liver biopsy to assess histologic severity and response to treatment, and the urgent need to validate noninvasive tests to replace liver biopsy—to determine treatment initiation, response, futility, and the need for combination therapy with multiple drugs. Conclusion: In this review, we aim to dissect each of these challenges and attempt to provide suggested solutions while fully realizing that knowledge gaps still exist where future research is likely to provide urgently needed answers.

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“…Owing to its generally asymptomatic nature and the lack of routine noninvasive screening tools, the true prevalence of NASH is unknown, but it is estimated to be between 1.5% and 6.5% globally . Patients with NASH—especially those with advanced fibrosis—have an increased risk for progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC) . NASH is projected to become the leading indication for liver transplantation in the near future …”

mentioning

confidence: 99%

The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials

et al. 2019

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Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum markers of fibrosis in 475 patients with NASH with bridging fibrosis (F3) or compensated cirrhosis (F4) enrolled in two phase 2b, placebo‐controlled trials of simtuzumab. The trials were terminated after 96 weeks because of lack of efficacy, so data from treatment groups were combined. Liver biopsies and HVPG measurements (only for patients with F4 fibrosis) were collected at screening and at weeks 48 and 96. Patients were assessed for Ishak fibrosis stage, hepatic collagen content and alpha‐smooth muscle actin (by morphometry), NAFLD Activity Score (NAS), and serum markers of fibrosis. Associations with progression to cirrhosis (in patients with F3 fibrosis) and liver‐related clinical events (in patients with F4 fibrosis) were determined. Progression to cirrhosis occurred in 22% (48/217) of F3 patients, and liver‐related clinical events occurred in 19% (50/258) of patients with cirrhosis. Factors significantly associated with progression to cirrhosis included higher baseline values of and greater increases in hepatic collagen content, level of alpha‐smooth muscle actin, and Enhanced Liver Fibrosis score. Similar factors, plus lack of fibrosis stage improvement (hazard ratio, 9.30; 95% confidence interval, 1.28‐67.37), higher HVPG at baseline, and greater increase in HVPG over time, were associated with an increased risk of liver‐related clinical events in patients with cirrhosis. Disease progression was not associated with the NAS at baseline or changes in NAS during treatment after adjustment for fibrosis stage. Conclusion: In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.

show abstract

Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey Data

Cited by 204 publications

References 24 publications

NASH‐related cirrhosis: An occult liver disease burden

NASH‐related cirrhosis: An occult liver disease burden

Looking Into the Crystal Ball: Predicting the Future Challenges of Fibrotic NASH Treatment

The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials

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