No abstract

International cohort study 458 biopsy proven NAFLD Bridging fibrosis F3 (n=159) Liver cirrhosis F4 (n=299) Vascular events Non-hepatic cancers All deaths or liver transplantation Decompensation Moderate alcohol consumption

Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

Summary Background Several recent studies have shown a strong association between non‐alcoholic steatohepatitis (NASH) and chronic kidney disease. Aim To examine the relationship between changes in liver histology and renal function in patients with NASH. Methods The present analysis represents a post hoc analysis of a recently published trial that included 261 patients with NASH who were treated with lifestyle modifications during 52 weeks. Kidney function was evaluated through Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rates (eGFR, mL/min/1.73 m2) overtime. We explored correlations between the kidney function and improvement in histological outcomes at 52 weeks. Results Interestingly, a one‐stage reduction in fibrosis (r = 0.20, P < 0.01) and resolution of NASH (r = 0.17, P < 0.01) were significantly correlated with an improvement in the kidney function. The eGFR values significantly increased in patients with fibrosis improvement (+7.6 ± 6.5 mL/min/1.73 m2), compared to those without fibrosis improvement (−1.98 ± 6.4 mL/min/1.73 m2) (P < 0.01) at end of treatment (EOT). Likewise, NASH resolution was associated with an increase in eGFR compared with patients without NASH resolution (2.32 ± 7.8 mL/min/1.73 m2 vs. −1.04 ± 5.9 mL/min/1.73 m2, P = 0.04) at EOT. After controlling for the confounders, the association between fibrosis improvement, NASH resolution and eGFR change remained significant (P < 0.05 for both). Conclusions Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in NASH. As new drugs for NASH emerge, studies should address whether improvement in histology in response to pharmacotherapies yield the same improvement in kidney function as weight loss.

Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] 5 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR 5 0.04, 95% CI 0.005-0.49; P 5 0.01), normal levels of alanine aminotransferase at the end of intervention (OR 5 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR 5 0.89, 95% CI 0.83-0.97; P 5 0.01), and a nonalcoholic fatty liver activity score 5 (OR 5 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of 46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff 69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) Conclusions: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score 5 may be useful to identify NASH resolution in patients under lifestyle intervention.