Letter to the editor: Spontaneous regression of cirrhosis: A paradigm shift in our understanding of the natural history of NASH

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]