CON: Should patients with nonalcoholic steatohepatitis fibrosis undergo bariatric surgery as a primary treatment?

Short abstract

Content available: Author Interview and Audio Recording

Watch the interview with the author.

Listen to an audio presentation of this article.

KEY POINTS

• Bariatric surgery (BS) is currently neither commonly pursued by eligible patients nor universally available.

• Only highly motivated patients should pursue BS, given its costs, risk for complications, and need for long‐term follow‐up and compliance. There are alternate therapies with evidence to support their use.

• Critical data are still missing to confirm the efficacy and safety of BS.

INTRODUCTION

There are currently more than 2.5 million patients with nonalcoholic steatohepatitis (NASH) with advanced fibrosis (F3‐F4) in the United States, ¹ , ² and this population is expected to grow to nearly 8 million by 2030. ³ There is a pressing need to identify an effective NASH treatment that is widely accessible, generally acceptable to patients, and strongly supported by evidence‐based data.

Recent literature suggests that BS may be an effective therapy for the treatment of NASH fibrosis. However, BS is not ready to be recommended as a primary treatment because of systemic, patient, and knowledge barriers.

SYSTEMIC BARRIERS

Limited availability

Although the annual volume of BS in the United States has increased by almost 1.6‐fold over the past decade, the absolute number of surgeries performed remains miniscule (256,000 in 2019) compared with the millions of eligible patients based on obesity and medical comorbidities (Figure 1). In addition, the growth rate of BS is reduced by the fact that a growing proportion of the annual cases, up to 16% in 2019, are revisions of prior procedures. A study conducted based on the National Inpatient Sample data suggested that the low utilization rate of BS is highly correlated with limitations in bariatric surgeon availability. ⁴ The volume of BS is simply insufficient to address the growing NASH epidemic.

FIGURE 1.

Estimate of BS numbers, 2011–2019. The ASMBS total bariatric procedure numbers are based on the best estimation from available data. Asterisk indicates new methodology for estimating outpatient procedures done at nonaccredited centers. Graph is from the ASMBS website (https://asmbs.org/resources/estimate‐of‐bariatric‐surgery‐numbers, accessed June 29, 2021)

Insurance restrictions

Insurance adds substantial barriers to the pursuit of BS. Regions in the United States that underuse BS often do not consider it an essential health benefit under the Affordable Care Act. ⁵ A recent survey showed that 95% of insurance policies require preauthorization, 87% require medical weight management before surgery, 43% limit coverage to centers of excellence, and 21% do not cover revisions. ⁶ Furthermore, many policies impose pre‐BS requirements (e.g., primary care provider letter, cardiac evaluation, pulmonary evaluation, psychiatric evaluation), which were found to delay surgery and encourage dropout. ⁷

PATIENT BARRIERS

Eligibility restrictions

Candidates for BS are highly selected. For instance, in most published BS study cohorts, participants were required to undergo a multidisciplinary evaluation, enroll in an intensive nutrition program, and be reevaluated to confirm their eligibility for BS. ⁸ Often candidates are asked to undergo a preoperative mental health evaluation to screen for and address substance use disorders or other psychiatric disorders. Cardiac and pulmonary issues, which are common among patients being evaluated for BS, must also be assessed before BS. This results in a selection bias in these cohort studies. Thus, the majority of patients with fibrotic NASH do not fit the profile of those actually undergoing successful preselection for surgery.

Short‐term safety concerns

Despite continued improvement in surgical techniques, surgical complications remain a substantial risk for any patients undergoing BS. Anastomotic leaks, one of the most dreaded complications with a high mortality rate of up to 15%, can occur in up to 4% to 7% of cases. Significant postoperative bleeding has been reported in nearly 11% of cases, 15% of which required surgical intervention. Other complications, such as infections, marginal ulcers, and spontaneous perforation, also occur with some frequency. As a result, BS carries an overall mortality rate of nearly 2% in the first 30 days ⁹ and is increased up to 16% in patients with decompensated cirrhosis. ¹⁰ These numbers may be declining in the most contemporary studies, because there is a shift toward laparoscopic sleeve gastrectomy and away from Roux‐en‐Y gastric bypass. ¹¹

Long‐term challenges

According to the 2019 multisociety guidelines, lifelong lifestyle modification and medical care are highly recommended. ¹² All types of BS are associated with vitamin and mineral deficiencies that can persist for up to 10 years postoperatively. After BS, healthy eating habits and regular exercise must be continued to prevent weight regain and need for revision. Despite the importance of continued follow‐up, a multicenter cohort study showed that medical follow‐up decreases to 40% after 24 months, and this drop‐off is predicted by loss of employment, highlighting the challenges of long‐term time commitment and financial burden faced by many BS patients. ¹³

KNOWLEDGE BARRIERS

Lack of randomized controlled trials

Although cohort studies with paired liver biopsies have shown that BS can achieve NASH resolution and fibrosis regression in 40% to 60% of subjects, ¹⁴ , ¹⁵ no true randomized controlled trial of BS has been reported. This exclusion of a control arm should not be overlooked. In a 2019 meta‐analysis of medical therapies for NASH, 25% of patients who received placebo had an improvement in their histological steatohepatitis by at least two points, and 21% were seen to have an improvement in liver fibrosis. ¹⁶ In fact, this placebo effect can be statistically significant and can even occur in the absence of weight loss (Table 1). There is no reason to suspect that studies involving BS are immune to this placebo effect; therefore, a randomized controlled trial is needed to validate the efficacy of BS.

TABLE 1.

Fibrosis regression in the control arms of NASH trials

Trial name (year of publication)	Placebo arm size (n)	Duration (weeks)	Fibrosis regression ≥1 Stage	Mean baseline fibrosis (F0‐F4 ± SD)	Mean weight loss in the placebo
SEMA NASH (2021)	80	72	33%	2.2 ± 0.8	1%
REGENERATE (2019)	311	72	23%	2.5 ± 0.5	−0.7 kg
PIVENS (2010)	83	96	31%	1.6 ± 1.1	No weight loss
LEAN (2016)	22	48	14%	2.3 ± 1.3	0.7%
FLINT (2014)	142	18	21%	1.8 ± 1	<0.5 kg

Note: In all four trials, all patients received standardized lifestyle counseling.

Potential excessive weight loss

Many studies on lifestyle interventions for NASH have shown that only 5% to 10% total body weight (TBW) loss is needed to achieve NASH reversal. ¹⁷ , ¹⁸ The degree of weight loss associated with BS, up to 25% to 45% TBW loss for Roux‐en‐Y gastric bypass, may simply be unnecessary, excessive, and does not further impact liver disease. A recent study also suggests that the often touted endocrine benefits of BS could be similarly derived from weight loss through lifestyle interventions. ¹⁹ Even in patients with unsuccessful lifestyle interventions, the necessary TBW loss can be achieved through other substantially less invasive weight loss therapies, including reversible endoscopic bariatric procedures ²⁰ , ²¹ and semaglutide. ²²

Conflicting and insufficient data

It is important to note that NASH fibrosis progression occurred in up to 12% of BS patients in the 2019 meta‐analysis ¹⁵ and 16% in the 2020 five‐year prospective study. ⁸ In addition, data are lacking on the safety and efficacy of BS for patients with nonalcoholic fatty liver disease and near‐normal body mass index, who make up nearly 40% of the global nonalcoholic fatty liver disease population ²³ and will likely benefit from non‐BS interventions.

CONCLUSION

Weight loss is the most effective therapy for NASH fibrosis. Diet, exercise, and behavioral/dietary counseling are the cornerstones of management. Patients who are refractory to lifestyle changes should have a thorough evaluation to understand the etiology of their metabolic syndrome, their level of motivation for change, and the types of therapy best suited to their needs. BS may be an effective treatment of NASH fibrosis in patients who are insured, compliant, motivated to make a lifelong change, and live in a region where BS is available. However, additional research is needed to confirm the efficacy of BS and delineate which patient characteristics are best suited to undergo an invasive, irreversible procedure.

CONFLICT OF INTEREST

Nothing to report.

Newton EB, Pan J, Chung W. CON: Should patients with nonalcoholic steatohepatitis fibrosis undergo bariatric surgery as a primary treatment?. Clinical Liver Disease. 2022;20:9–12. 10.1002/cld.1226