Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: A propensity matched analysis

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Highlights

  • Bariatric surgery on the incidence of NASH and HCC is unclear in obese patients .

  • Performed large propensity matched analysis of bariatric surgery and non-surgery patients.

  • Found lower incidences of NASH and HCC after bariatric surgery over 7-year follow-up.

Abstract

Introduction

Obesity is a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Bariatric surgery can provide durable weight-loss, but little is known about the later development of NASH and HCC after surgery.

Methods

Bariatric surgery (n = 3,410) and obese controls (n = 46,873) from an institutional data repository were propensity score matched 1:1 by demographics, comorbidities, BMI, and socioeconomic factors. Comparisons were made through paired univariate analysis and conditional logistic regression.

Results

Total of 4,112 patients were well matched with no significant baseline differences except initial BMI (49.0 vs 48.2, p = 0.04). Bariatric group demonstrated fewer new-onset NASH (6 0.0% vs 10.3%, p < 0.0001) and HCC (0.05% vs 0.34%, p = 0.03) over a median follow-up of 7.1 years. After risk-adjustment, bariatric surgery was independently associated with reduced development of NASH (OR 0.52, p < 0.0001).

Conclusions

Bariatric surgery is associated with reduced incidence of NASH and HCC in this large propensity matched cohort. This further supports the use of bariatric surgery for morbidly obese patients to ameliorate NASH cirrhosis and development of HCC.

Introduction

Incidences of non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) are increasing throughout the United States.1,2 A large contributing factor may be the rise of obese adults, as this trend is increasingly affecting adolescents, as well. The progression of NASH from non-alcoholic fatty liver disease (NAFLD) occurs in approximately 10–25% of patients3 and can lead to significant risks in liver-related mortality due to the development of hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). It is projected that more than 10% weight loss is needed in order to improve NASH,4 however, weight loss modification through lifestyle changes alone account for only 3–5% total body weight loss on average and does not provide durable weight loss over time.5 Two first-line medications (Vitamin E and pioglitazone) have been used to augment this effect,6 however there are concerns due their association with other cancers and morality risk, also in their lack of improving hepatic fibrosis.7 Additionally, the effectiveness of these medications was only studied in non-diabetic patients which leaves limited options for the greater proportion of obese patients that are also diabetic.

Bariatric surgery has shown to provide sustained weight loss throughout the course of a patient's lifetime,8 and most patients who are candidates for bariatric surgery have some degree of NAFLD.6 Previous studies have shown that bariatric surgery not only improves steatosis in NASH, but may also improve hepatic fibrosis even in patients who may have other metabolic diseases including diabetes mellitus type II (DM2).5,7,9,10 However, this was not a consistent finding since a few studies also showed worsening hepatic fibrosis over time.5,7,9, 10, 11 It is due to this concern that despite guidelines suggesting the benefit of bariatric surgery in reducing the progression to NASH, there is still no definitive recommendation on its routine use.6,11 This may, in part, have contributed to the overall decrease in the number of bariatric surgery procedures performed in patients with NAFLD from 2004-2012.12 Clearly more evidence is needed to further understand this association.

There is a lack of case-controlled studies in the literature highlighting the effect of bariatric surgery on NASH5,7 and the few studies on bariatric surgery and HCC only analyzed its prevalence in a bariatric population and did not address the development of new HCC after bariatric surgery.13,14 Most studies also have relatively short follow up times as little as one month to only five years.5,14 We hypothesized that performing case-matching through propensity score analysis of all patients who received bariatric surgery with long-term follow up will be able to better elucidate the risk of developing NASH and HCC after bariatric surgery.

Section snippets

Patients

All adult patients who underwent bariatric surgery (including RYGB, sleeve gastrectomy, and adjustable gastric banding) for morbid obesity (n = 3,410) at a single academic institution between 1985 and 2015 were identified retrospectively from a prospectively maintained database.15 To identify an appropriate control group, an institutional clinical data repository (CDR) of all routine outpatient visits from the same academic institution was queried to identify a non-operative cohort of 46,873

Results

A total of 3,410 patients who received bariatric surgery were evaluated and compared with 45,750 obese control patients who did not receive bariatric surgery from the same institutional data repository. Both patient groups varied in all demographic factors, and in almost all baseline comorbidities evaluated (Supplemental Table 1).

Propensity case-matching resulted in the inclusion of 2,057 bariatric surgery patients and 2,055 control patients (Table 1). The two groups were well matched in all

Discussion

Bariatric surgery was associated with fewer cases of NASH by 48% through risk-adjusted analysis compared to propensity score matched controls in this large cohort of patients with extended follow up. Through case-controlled propensity score matching, we found bariatric patients had decreased incidences of both NASH and HCC even when cases were matched on demographics and comorbidity risk factors such as DM2, GERD, alcohol and tobacco use. The one bariatric patient with HCC had a questionable

Conclusion

Propensity match analysis of a large cohort of bariatric surgery patients compared with obese non surgery controls revealed patients who had undergone bariatric surgery had fewer new cases of NASH and HCC during with extended follow up. Further risk adjustment also showed bariatric surgery was associated with fewer cases of NASH by 48%. These results highlight the importance of bariatric surgery offering more than a procedure for sustained weight loss, but also in its potential to further abate

Conflicts of interest

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Acknowledgments

Funding Sources for Minyoung Kwak: NCI Cancer Center Support Grant P30 CA44579 Farrow Fellowship, University of Virginia.

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