Bariatric Surgery for Fatty Liver Disease

Overseen By Allison Wolf

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Amiodarone, Methotrexate, Glucocorticoids, others

Disqualifiers: Cardiovascular events, Cancer, Alcohol, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how bariatric surgery, specifically Vertical Sleeve Gastrectomy (a type of weight-loss surgery), can treat nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). These obesity-linked conditions could lead to liver transplants. Researchers aim to understand the relationship between liver functions like fat burning and glucose production, the severity of liver disease, and how these change after surgery. The trial seeks to determine if pre-surgery liver function can predict the liver's response to surgery. Suitable candidates for this trial include individuals with NAFLD or NASH, a body mass index (BMI) between 30 and 55, and a willingness to undergo surgery. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on improving liver health through surgery.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications associated with nonalcoholic fatty liver disease, such as amiodarone, methotrexate, and oral glucocorticoids, for more than 4 weeks within the last 2 months before screening. You also need to stop taking pioglitazone or high-dose vitamin E within the last 2 months before screening.

What prior data suggests that bariatric surgery is safe for treating fatty liver disease?

Research has shown that bariatric surgery, such as Vertical Sleeve Gastrectomy (VSG), is generally safe and well-tolerated. Studies have found that this surgery often leads to significant improvements in liver health without major liver-related side effects. Specifically, no significant reports of liver problems have emerged after surgery. Additionally, VSG has been linked to reduced liver scarring and fat buildup in about 60% of patients. This suggests that the surgery can help improve liver function and reduce liver damage in people with fatty liver disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for fatty liver disease focus on lifestyle changes, like diet and exercise, or medications that target liver inflammation. However, Vertical Sleeve Gastrectomy (VSG) is unique because it physically reduces the size of the stomach, which can lead to significant and sustained weight loss. This weight loss can directly reduce liver fat and improve liver health, offering a more immediate and potentially more effective solution compared to traditional methods. Researchers are excited about VSG because it targets the root cause of fatty liver disease—excess weight—potentially leading to longer-lasting improvements in liver function.

What evidence suggests that bariatric surgery is effective for fatty liver disease?

Research has shown that vertical sleeve gastrectomy (VSG), the treatment under study in this trial, effectively treats nonalcoholic fatty liver disease (NAFLD). Studies indicate that VSG significantly reduces liver fat and improves liver health for most patients. In one study, liver tests showed improvement in all patients, with some experiencing even greater benefits. Another study found that VSG helped about 60% of patients reduce liver scarring and fat buildup. These positive results are linked to the weight loss and body changes encouraged by VSG. ^{1 4 5 6 7}

Who Is on the Research Team?

Sayeed Ikramuddin, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults aged 18-67 with a BMI of 30.0-55.0 kg/m2, diagnosed with NASH (NAS ≥3) or non-NASH/NAFLD (NAS ≤3), and possibly T2DM or prediabetes are eligible for this trial focused on liver health in relation to obesity. Participants must consent to surgery, live near the clinic for follow-ups, have insurance covering obesity treatments, and be suitable for liver biopsy.

Inclusion Criteria

Expect to live or work within approximately three-hour traveling time from the study clinic for the duration of the one-year trial

Your body mass index (BMI) is between 30 and 55.

Diagnosed with NASH with a total NAS ≥ 3 including a ballooning score of at least 1, or non-NASH/NAFLD with a total NAS ≤3, or Diagnosed with T2DM or prediabetes, HbA1c< 8% , or CAP score greater than or equal to 248 on Fibroscan

Exclusion Criteria

Serum c-peptide <1.0 ng/ml post prandial.

Exclusions may also be made at the discretion of the attending physician or the eligibility committee.

I have not taken specific medications that could cause fatty liver disease in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Assessment

Baseline measurements of hepatic energy fluxes using MRS and preoperative liver biopsies for NAS score determination

4 weeks

1 visit (in-person)

Treatment

Participants undergo Vertical Sleeve Gastrectomy (VSG) as a bariatric surgical procedure

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in hepatic energy fluxes and NAS score post-surgery

12 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Vertical Sleeve Gastrectomy (VSG)

Trial Overview The study is testing how Vertical Sleeve Gastrectomy (VSG), a type of bariatric surgery, affects liver function—specifically fat burning and glucose production—in patients with varying severities of fatty liver disease related to obesity.

How Is the Trial Designed?

Group I: Vertical Sleeve Gastrectomy (VSG) Experimental Treatment 1 Intervention

Bariatric surgical procedure

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

In a 2-year study of 66 adolescents and young adults undergoing vertical sleeve gastrectomy (VSG), patients experienced significant weight loss of 25.3%, but also a concerning 8.5% decline in total hip bone mineral density (BMD), indicating potential negative effects on bone health.

The study found that VSG led to a decrease in volumetric BMD at the distal radius and tibia, primarily due to loss of trabecular bone, which may increase the risk of skeletal fragility in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study. Mitchell, DM., Singhal, V., Animashaun, A., et al.[2023]

In a study of 200 patients, laparoscopic vertical sleeve gastrectomy (VSG) was found to have a shorter operative time and hospital stay compared to single-stage laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS).

However, while VSG is technically simpler and has promising outcomes, BPD/DS resulted in significantly greater excess weight loss at 6 months post-surgery, indicating it may be more effective for long-term weight management in morbidly obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of vertical sleeve gastrectomy versus biliopancreatic diversion. Sucandy, I., Titano, J., Bonanni, F., et al.[2021]

In a study of over 513,000 patients who underwent vertical sleeve gastrectomy (VSG), staple-line reinforcement (SLR) methods like buttressing (BR) and oversewing (OS) were found to significantly reduce the rates of overall and major bleeding compared to no reinforcement (NR), although they resulted in longer operative times and hospital stays.

No SLR method significantly reduced the incidence of leaks, but bleeding was linked to a higher occurrence of leaks and increased morbidity and mortality, suggesting that using SLR techniques could improve patient outcomes after VSG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database. Aboueisha, MA., Freeman, M., Allotey, JK., et al.[2023]

Vertical sleeve gastrectomy (VSG) led to significant weight loss in adolescents with obesity, with body weight decreasing from an average of 136.6 kg to 87.4 kg over 52 weeks (P < .001).

After VSG, adolescents showed a reduced willingness to exert effort for high-calorie candies, indicating a decreased reward value for these foods, which may contribute to long-term weight loss and maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vertical sleeve gastrectomy in adolescents reduces the appetitive reward value of a sweet and fatty reinforcer in a progressive ratio task. Abdeen, GN., Miras, AD., Alqahtani, AR., et al.[2021]

After 5 years post-vertical sleeve gastrectomy (VSG), patients maintained significant weight loss, with a mean body mass index (BMI) reduction from 46.2 kg/m2 to 32.9 kg/m2, indicating the procedure's long-term efficacy in obesity management.

The surgery led to substantial improvements in obesity-related conditions, with 63% of patients experiencing remission of type 2 diabetes and 60% for hypertension at 5 years, although there was an increase in gastroesophageal reflux disease (GERD) cases over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Outcomes After Vertical Sleeve Gastrectomy for Severe Obesity: A Prospective Cohort Study. Flølo, TN., Andersen, JR., Kolotkin, RL., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5061986/

The Effect of Bariatric Surgery on the Spectrum of Fatty ... In another prospective trial, liver biopsy demonstrated improvement of steatosis in all 26 patients, including 12 of the 26 exhibiting improvement of greater ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1479666X23000847

The impact of bariatric surgery on liver enzymes in people ... Bariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity.

3. hbsn.amegroups.org hbsn.amegroups.org/article/view/136089/html

Clinical advantages and efficacy of sleeve gastrectomy in the ... Existing studies have demonstrated that both laparoscopic SG and RYGB significantly improve NAFLD, particularly in reducing liver fat accumulation, enhancing ...

4. cghjournal.org cghjournal.org/article/S1542-3565%2808%2900831-8/fulltext

Effect of Bariatric Surgery on Nonalcoholic Fatty Liver ... Steatosis, steatohepatitis, and fibrosis appear to improve or completely resolve in the majority of patients after bariatric surgery–induced weight loss.

5. mdpi.com mdpi.com/2077-0383/14/12/4012

Impact of Bariatric Surgery and Endoscopic Therapies on ... Vertical sleeve gastrectomy (VSG) provided comparable hepatic benefits, significantly reducing liver fibrosis and steatosis in approximately 60% of patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03587831

NCT03587831 | Vertical Sleeve Gastrectomy and Lifestyle ... The pilot study proposed in this protocol will determine whether patients with a BMI of 35-60 kg/m2 will consent to liver biopsy, accept randomization to VSG, ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2803481

Outcomes After Bariatric Surgery in Patients With Obesity ... Bariatric surgery was significantly associated with lower risks of major adverse cardiovascular events and all-cause mortality.