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Weight loss and liver

Weight loss can significantly reduce features of NASH

Patients whose NASH persisted one year after surgery (n=12) had lost significantly less weight (change in BMI, 9.1±1.5) than those without NASH (change in BMI, 12.3±0.6) (p=0.005)
All lifestyle patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis

Weight loss through both bariatric surgery and lifestyle modification can significantly reduce features of nonalcoholic steatohepatitis (NASH), according to two studies published in Gastroenterology, the official journal of the American Gastroenterological Association. There are currently no approved therapies for NASH. Physicians recommend that patients with NASH reduce their weight, eat a balanced diet, engage in physical activity, and avoid alcohol and unnecessary medications.

“While the underlying cause of NASH is unclear, we most commonly see this condition in patients who are middle-aged and overweight or obese," said Dr Giulio Marchesini from University of Bologna, Italy, and lead author of the editorial, 'Weight Loss for a Healthy Liver', summarising these two studies. "These two large prospective cohort studies strengthen the evidence that, no matter how you lose weight, weight loss improves liver health. Both bariatric surgery for morbidly obese patients or lifestyle modifications are viable options. These two studies provide a benchmark for any future pharmacologic intervention in NASH, across the entire spectrum of obesity.”

Bariatric surgery

For appropriate morbidly obese patients with NASH who have previously failed to lose weight through lifestyle modifications, bariatric surgery may be considered. In the study, Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients, Guillaume Lassailly and colleagues from France report that, one year after bariatric surgery, NASH had disappeared from 85 percent of patients and reduced the pathologic features of the disease after one year of follow-up. NASH disappeared from a higher proportion of patients with mild NASH before surgery (94 percent) than severe NASH (70 percent).

The authors note that the effects of bariatric surgery in patients with nonalcoholic fatty liver disease (NASH) are not well established. As a result, they performed a prospective study to determine the biological and clinical effects of bariatric surgery in patients with NASH.

From May 1994 through May 2013, 109 morbidly obese patients with biopsy-proven NASH underwent bariatric surgery at the University Hospital of Lille, France (the Lille Bariatric Cohort). Clinical, biological, and histologic data were collected before and one year after surgery.

One year after surgery, NASH had disappeared from 85% of the patients (95% confidence interval [CI]: 75.8%−92.2%). Compared with before surgery, patients had significant reductions in mean ± SD body mass index (BMI, from 49.3±8.2 to 37.4±7) and level of alanine aminotransferase (from 52.1±25.7 IU/L to 25.1±20 IU/L); mean levels of γ-glutamyltransferases were reduced from 51 IU/L before surgery (interquartile range [IQR], 34−87 IU/L) to 23 IU/L afterward (IQR, 14−33 IU/L) and mean insulin resistance index values were reduced from 3.6±0.5 to 2.9±0.5 (p<0.01 for each comparison). NASH disappeared from a higher proportion of patients with mild NASH before surgery (94%) than severe NASH (70%) (p<0.05) according to Brunt score.

In histologic analysis, steatosis was detected in 60% of the tissue before surgery (IQR, 40%−80%) but only 10% one year after surgery (IQR, 2.5%−21.3%); the mean nonalcoholic fatty liver disease score was reduced from 5 (IQR, 4−5) to 1 (IQR, 1−2) (each p<0.001). Hepatocellular ballooning was reduced in 84.2% of samples (n=69; 95% CI: 74.4−91.3) and lobular inflammation in 67.1% (n=55; 95% CI: 55.8−77.1). According to Metavir scores, fibrosis was reduced in 33.8% of patients (95% CI: 23.6%−45.2%).

Patients whose NASH persisted one year after surgery (n=12) had lost significantly less weight (change in BMI, 9.1±1.5) than those without NASH (change in BMI, 12.3±0.6) (p=0.005). Patients who underwent laparoscopic gastric banding lost less weight (change in BMI, 6.4±0.7) than those who underwent gastric bypass (change in BMI, 14.0±0.5) (p<0.0001), and a higher proportion had persistent NASH (30.4% vs 7.6% of those with gastric bypass; p=0.015).

They authors concluded that bariatric surgery induced the disappearance of NASH from nearly 85% of patients and reduced the pathologic features of the disease after one year of follow-up. It could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications, they write, however more studies are needed to determine the long-term effects of bariatric surgery in morbidly obese patients with NASH.

Lifestyle modifications

In their paper, Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis, Eduardo Vilar-Gomez and colleagues from Cuba report that a weight reduction of 10 percent or more, induced by a comprehensive lifestyle programme, is necessary to bring about NASH resolution and reverse scarring of the liver in overweight and obese patients.

They conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks (June 2009 through May 2013), at a tertiary medical centre in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analysed histologically.

Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios=1.1−2.0; p<0.01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects who lost <5% of their weight (p<0.001).

All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%−10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%.

To a lesser degree, modest weight loss (7 to 10 percent) reduced disease severity in certain subsets of patients, including male patients and those without diabetes. Conversely, 93 percent of the patients with little or no weight reduction (less than 5 percent) experienced worsening of liver scarring.

This is the first large prospective study conducted in real-world clinical practice that explores the potential benefit of a 12-month lifestyle intervention on NASH-related features, as well as the cut off points for positive outcomes. While promising, less than 50 percent of patients achieved the necessary weight loss goal of 7 to 10 percent, providing a stark reminder of the sustainability of weight loss interventions, the researchers write. 

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