In a pilot randomized controlled trial, we found administration of G-CSF to improve liver function and increase survival times in patients with severe AH, compared with standard therapy. We found no evidence for benefit of adding NAC to G-CSF. These findings require confirmation in larger trials. ClincialTrials.gov, number: NCT02971306.

Background: The FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score

We read with great interest the study published by Luis Calzadilla-Bertot et al. (1) The study has proposed the ABIDE score, which is a simple bedside tool that aims to predict decompensation in a selected cohort of patients with NAFLD with cirrhosis. However, there are issues that need further clarification.First, with regard to alcohol consumption, the authors need to clarify whether only significant alcohol consumption was excluded or any alcohol consumption either at baseline or at follow-up was excluded. Emerging evidence does indicate that any degree of alcohol consumption not only worsens liver disease status in NAFLD but also increases the risks for type 2 diabetes, which is one of the integral components of the score. (2,3) Similarly, the degree of glycemic control as well as the spectrum of oral antidiabetic use at baseline may further help to substratify the risks in these patients.Second, although the subgroup analysis found no differences with regard to use of baseline betablockers, it would be of interest to know the type and dosage of beta-blocker used at baseline, which may influence the outcomes. (4) Additionally, there appears to be large variations in the rate of decompensation between the derivation and validation cohort (27% vs. 54%). These variations, although not conclusive, are indicative of an inappropriate calibration of the model and raise concerns about the external validation.Third, as the model is derived from a cohort of patients with biopsy-proven NASH, it is important to know whether the patient was receiving medications for NASH cirrhosis. (5) Finally, it is important to note that this model is valid only in NAFLD with cirrhosis; it will be crucial especially to identify patients in this group to target studies with decompensation as the primary endpoint.Future modifications of ABIDE may find its application in the other important NAFLD cohorts.Author Contributions: A.K. was responsible for the draft of the letter. S.T. and A.R. were responsible for the draft and critical revision of the letter. V.S. was responsible for critical revision of the letter.

No abstract

To the editor, We read with great interest the study by Sanyal et al. about improved clinical outcomes with regression of cirrhosis in NASH. [1] An astounding 16% of patients attained regression of cirrhosis with consistent changes in noninvasive tests (NITs). The observation that NITs correlate with changes in fibrosis suggests that temporal trends of NITs may act as a surrogate of histological progression or regression of fibrosis. This is very relevant in daily clinical practice where routine and, particularly, paired liver biopsies are often not feasible. However, a caveat is that interval follow-up with NITs that incorporate age may be erroneous with falsely high values even in regressors as patients become older. Thus, age-independent NITs like elastography may be preferable.Reversal of cirrhosis is now well documented where the underlying etiology is treatable. [2] Simtuzumab and selonsertib have been shown to be no better than placebo. Hence, regression of cirrhosis in these patients was presumably spontaneous. Intriguingly, although, patients in whom there was a regression of cirrhosis had lower body mass index (BMI) and better glycaemic control at baseline compared to nonregressors; there was no difference in change in BMI or glycemic control on follow-up between the two groups. Septal thickness, number, and size of nodules are key histological parameters that have been shown to correlate with regression of cirrhosis in viral hepatitis. [3,4] Indeed, cirrhosis with large nodules and thin septa have higher potential for reversibility whereas atrophic cirrhosis with small nodules and large septa are unlikely to regress. [4] Although not a part of the NASH Clinical Research Network reporting system, incorporation of these data would have added further granularity to the study.Finally, ongoing steatohepatitis accelerates fibrosis progression. In this study, resolution of NASH with improvement in ballooning and lobular inflammation was documented in regressors. [1] It is reasonable to speculate that resolution of NASH with available pharmacotherapy may halt the progression of fibrosis, creating the grounds for its reversal. Indeed, reduced hepatic decompensation and increased transplant-free survival with long-term use of vitamin E have been observed in a recent retrospective study and needs to be further evaluated. [5]