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Reversing fatty liver disease

RYGB can reverse fatty liver disease and non-alcoholic steatohepatitis

Preoperative AST (p=0.001) and ALT (p<0.001) were univariably significant predictors of clinically significant fatty livers after RYGB

Roux-en-Y gastric bypass (RYGB) surgery maybe a promising approach to reverse fatty liver disease, and importantly, a potential future therapeutic option for the treatment and reversal of non-alcoholic steatohepatitis (NASH), according to a study by researchers from the Cleveland Clinic, OH.

It is known that RYGB leads to improvements in the pathophysiology that contributes to obesity-related NASH however, whether obesity-related fibrosis improves is unclear. In the paper, ‘Reversal of fibrosis in patients with nonalcoholic steatohepatosis after gastric bypass surgery’, published in BMC Obesity, the researchers hypothesised that RYGB reverses NASH and fibrosis, and indocyanine green (ICG) clearance provides a sensitive measure for detecting asymptomatic fatty liver disease. They also evaluated the diagnostic utility of ICG clearance relative to biochemical testing for detecting asymptomatic (but clinically important) fatty liver diseases before and after RYGB.

One-hundred-six bariatric surgical patients were enrolled; 105 patients ultimately had RYGB.. A subset of the 37 patients with histologically diagnosed NASH was re-evaluated once patients lost 60% of their preoperative excess weight or weight loss plateaued after surgery. The researchers performed biochemical liver function tests on 25 of these patients and repeat liver biopsies on 15.

Preoperative biochemical testing was obtained including aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALK), total bilirubin, albumin and prothrombin time (PT). Once patients lost 60% of their preoperative excess weight or weight loss had plateaued, both liver function and histology were reassessed. Follow-up biochemical testing was obtained including AST, ALT, ALK, total bilirubin, albumin and PT.

The liver was visually inspected during the RYGB before liver biopsy. Changes from before to after RYGB for each of the biochemical liver function tests (including AST, ALT, ALK, total bilirubin, albumin, and PT), ICG clearance and histological measures (including NAS steatosis, NAS lobular inflammation, NAS hepatocyte balloon, and fibrosis) were evaluated with paired t and Wilcoxon signed rank tests.

Outcomes

The average patient follow-up period was 487±86 days with an observed mean decrease in weight of 42±16 kg and a decrease in BMI15.6±6.1. There was a statistically significant but clinically unimportant reduction in serum albumin concentrations after RYGB of 4.4 versus 4.2mg/dl (p<0.001). Liver function tests and ICG k clearance values did not otherwise differ significantly.

At the time of RYGB surgery, 27 (26%) patients had normal liver histology; 41 (39%) patients had non-alcoholic fatty liver; 26 (25%) patients had NASH without fibrosis or with stage 1 or 2 fibrosis; and 11 (10%) patients had NASH with stage 3 or 4 fibrosis.

Of the 15 patients with pre- and post-RYGB surgery biopsies, 9/13 patients with substantial fatty liver disease had normalised histological features after weight loss, while the severity of fatty liver disease in the remainder of patients had either stabilized or reduced. The researchers observed improvement in steatosis (12/13 patients normalized with reduced severity in the remainder), decreased lobular inflammation (9/12 patients normalised with reduced severity in the remainder), reduced incidence of hepatocyte ballooning (11/12 patients normalised with reduced severity in the remainder) and fibrosis regression (12/15 patients with fibrosis normalised with reduced severity in the remainder.

All estimated correlations between the changes seen pre- and post-RYGB for biochemical liver function tests, non-invasive ICG k clearance, and histological measures ranged from 0.01 (between change in ALT and change in ICG k clearance value) to 0.54 (between change in total bilirubin and change in fibrosis). None of these correlations differed significantly from zero (Table 5).

Preoperative AST (p=0.001) and ALT (p<0.001) were univariably significant predictors of clinically significant fatty livers after RYGB. Both tests had moderate predictive ability of more advanced stages of fatty liver with an AUC of 0.72 (99.4% Cl 0.61 0.82) for AST and 0.76 (0.66, 0.85) for ALT, respectively. Other biochemical liver function tests and ICG k clearance values were not significant predictors of NASH.

Only 45 of 105 patients met the criteria for follow-up liver biopsy (NAS score >3 or fibrosis) and stable weight loss. Although the same NIH-based NAFLD criteria was used as in prior investigations, the researchers determined histological change (non-dichotomous data in rank order) to estimate the mean change from pre- to post-RYGB surgery. There were clinically important and statistically significant histologic improvements from before to after RYGB in steatosis, lobular inflammation, NAS hepatocyte ballooning and fibrosis.

“RYGB and weight loss in bariatric patients markedly improved steatosis, lobular inflammation, NAS hepatocyte ballooning and fibrosis,” the researchers concluded. “A 70% normalization rate of significant fatty liver disease and stable or reduced severity of fatty liver in the remaining patients suggests that RYGB surgery maybe a promising approach to reverse fatty liver disease, and importantly, a potential future therapeutic option for the treatment and reversal of NASH.”

To access this paper, please click here

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