Nonalcoholic Steatohepatitis Is Associated With Increased Mortality in Obese Patients Undergoing Bariatric Surgery

Goossens, Nicolas; Hoshida, Yujin; Song, Won‐Min; Jung, Minoa; Morel, Philippe; Nakagawa, Shigeki; Zhang, Bin; Frossard, Jean‐Louis; Spahr, Laurent; Friedman, Scott L.; Negro, Francesco; Rubbia‐Brandt, Laura; Giostra, Emiliano

doi:10.1016/j.cgh.2015.10.010

Cited by 53 publications

(41 citation statements)

References 33 publications

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“…Although our study allows for a clinically meaningful expansion of the literature, it is not without limitations. First, we were able to account for variability in follow‐up, but we were not able to adjust for important comorbid conditions (i.e., diabetes, cardiovascular disease), demographics (i.e., age), or subtypes (steatohepatitis versus fatty liver) known to impact fibrosis progression and mortality risk in NAFLD . This is of importance as our reference group included patients with simple steatosis and nonalcoholic steatohepatitis, which could have influenced our baseline estimates and comparisons.…”

Section: Discussionmentioning

confidence: 99%

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

et al. 2017

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Background Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. Methods Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0–4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement. Results 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19–2.11); stage 2, MRR, 2.52 (95% CI 1.85–3.42); stage 3, MRR, 3.48 (95% CI 2.51–4.83), and stage 4, MRR, 6.40 (95% CI 4.11–9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17–11.95); stage 2, MRR, 9.57 (95% CI 1.67–54.93); stage 3, MRR, 16.69 (95% CI 2.92–95.36); and stage 4, MRR, 42.30 (95% CI 3.51–510.34). Limitations Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group. Conclusion The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another.

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Section: Discussionmentioning

confidence: 99%

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

et al. 2017

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“…NAFLD is present in ~90% of patients who qualify for metabolic surgery and approximately 33% of these have biopsy proven non-alcoholic steatohepatitis (NASH) 77 , a precursor of more serious liver disease including cirrhosis and need for transplantation. In fact patients with NASH by biopsy have an increased risk of death within a median follow-up of 10.2 years after bariatric surgery 78 . Although medical management including weight loss, pioglitazone, vitamin E, pentoxifylline, ursodeoxycholic acid and most recently liraglutide has had variable effect, bariatric surgery has proven more effective 79 .…”

Section: Expected Benefit On Cvd Risk Factorsmentioning

confidence: 99%

Treatment of Obesity

Wolfe

Kvach

Eckel

2016

Circulation Research

488

192

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This review focuses on the mechanisms underlying, and indications for, bariatric surgery in the reduction of cardiovascular disease (CVD) as well as other expected benefits of this intervention. The fundamental basis for bariatric surgery for the purpose of accomplishing weight loss is the determination that severe obesity is a disease associated with multiple adverse effects on health which can be reversed or improved by successful weight loss in patients who have been unable to sustain weight loss by non-surgical means. An explanation of possible indications for weight loss surgery as well as specific bariatric surgical procedures is presented, along with review of the safety literature of such procedures. Procedures that are less invasive or those that involve less gastrointestinal rearrangement accomplish considerably less weight loss but have substantially lower perioperative and longer-term risk. The ultimate benefit of weight reduction relates to the reduction of the co-morbidities, quality of life and all-cause mortality. With weight loss being the underlying justification for bariatric surgery in ameliorating CVD risk, current evidence-based research is discussed concerning body fat distribution, dyslipidemia, hypertension, diabetes, inflammation, obstructive sleep apnea and others. The rationale for bariatric surgery reducing CVD events is discussed and juxtaposed with impacts on all-cause mortalities. Given the improvement of established obesity-related CVD risk factors following weight loss, it is reasonable to expect a reduction of CVD events and related mortality following weight loss in populations with obesity. The quality of the current evidence is reviewed and future research opportunities and summaries are stated.

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“…According to the current American Association for the Study of Liver Diseases guidelines, the minimal histologic requirements for diagnosing NASH include steatosis, lobular inflammation, and ballooning of hepatocytes. Although these criteria provide an overall categorization of a subtype of NAFLD that can be at risk for progressive liver disease, it also has created substantial uncertainty that is primarily related to the reliance on hepatocyte ballooning for diagnosing NASH and its disappearance as the endpoint of the “resolution of NASH” for clinical trials . It therefore became important to assess the predictive ability of the different histologic features in NAFLD and the reliability of these features in establishing the diagnosis of NASH …”

Section: Introductionmentioning

confidence: 99%

Nonalcoholic steatofibrosis independently predicts mortality in nonalcoholic fatty liver disease

Younossi

Stepanova

Rafiq

et al. 2017

Hepatology Communications

110

117

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Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD). The minimal pathologic criteria for NASH include hepatic steatosis, ballooning degeneration, and lobular inflammation. The resolution of NASH, which relies on the loss of ballooning degeneration, is subject to sampling and observer variability in pathologic interpretation. Ballooning is associated with advanced hepatic fibrosis in cross‐sectional studies but is not a predictor of mortality in NAFLD. Fibrosis staging, while still subject to some sampling variability, has less observer variability and is a robust predictor of liver‐related mortality in NAFLD. In this study, we hypothesize that, regardless of the diagnosis of NASH, the presence of steatofibrosis (steatosis accompanied by fibrosis) regardless of other pathologic features can also be a robust predictor of mortality in NAFLD. We used our previously reported cohort of patients with NAFLD with liver biopsies and long‐term mortality follow‐up. Cox proportional hazard models were used to determine the predictors of overall and liver‐related mortality. Of 209 enrolled NAFLD subjects, 97 can be classified as having steatofibrosis. During follow‐up (median 150 months), 64 (30.6%) patients died, with 18 (8.6%) from liver‐related causes. Adjusted for age, both diagnostic categories of NASH and steatofibrosis were significantly and similarly associated with liver‐related mortality (adjusted hazard ratio [aHR], 9.9; 95% confidence interval (CI), 1.3‐74.9; P = 0.027; aHR, 6.7; 95% CI, 1.5‐29.8; P = 0.013, respectively). However, only steatofibrosis showed independent association with overall mortality (aHR, 1.76; 95% CI, 1.02‐3.05; P = 0.043). Conclusion: Steatofibrosis and NASH are similarly associated with liver‐related mortality, but only steatofibrosis is associated with overall mortality in patients with NAFLD. Given the inherent observer variability in ballooning degeneration, a key diagnostic component of NASH, we suggest that steatofibrosis should be considered a viable diagnostic classification for NAFLD subjects at risk or adverse outcomes and provides a simpler endpoint for clinical trials of therapeutic agents. (Hepatology Communications 2017;1:421–428)

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Nonalcoholic Steatohepatitis Is Associated With Increased Mortality in Obese Patients Undergoing Bariatric Surgery

Cited by 53 publications

References 33 publications

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

Treatment of Obesity

Nonalcoholic steatofibrosis independently predicts mortality in nonalcoholic fatty liver disease

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