Natural history of metabolic dysfunction-associated steatotic liver disease (MASLD)
A prospective cohort study observed 1773 adults with MASLD for a median of 4 years. Mortality in the study population was higher than the expected age-related background rates. Mortality increased as the fibrosis stage increased. Patients with stage F4 fibrosis had significantly higher all-cause mortality (hazard ratio [HR] 3.9, 95% CI 1.8 to 8.4) and liver-related mortality (HR 12.7, 95% CI 1.8 to 88.6), compared with patients with stage F0 to F2 fibrosis. Any hepatic decompensation event was associated with an almost 7-fold increased risk of mortality. The most common decompensation events were encephalopathy and ascites.[15]Sanyal AJ, Van Natta ML, Clark J, et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N Engl J Med. 2021 Oct 21;385(17):1559-69.
http://www.ncbi.nlm.nih.gov/pubmed/34670043?tool=bestpractice.com
The risk of MASL progressing to cirrhosis or liver failure is minimal.[3]Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-835.
https://journals.lww.com/hep/fulltext/2023/05000/aasld_practice_guidance_on_the_clinical_assessment.31.aspx
http://www.ncbi.nlm.nih.gov/pubmed/36727674?tool=bestpractice.com
One study of patients with metabolic dysfunction-associated steatohepatitis (MASH) who underwent serial liver biopsies found that fibrosis stage progressed in 37%, remained stable in 34%, and regressed in 29%.[154]Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.
http://onlinelibrary.wiley.com/doi/10.1002/hep.21327/full
http://www.ncbi.nlm.nih.gov/pubmed/17006923?tool=bestpractice.com
Independent predictors of fibrosis progression included diabetes, a low initial fibrosis stage, and a higher body mass index. At a mean follow-up of 14 years, MASH is associated with increased overall mortality, which was primarily a result of cardiovascular disease and to a lesser extent liver-related causes.[154]Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.
http://onlinelibrary.wiley.com/doi/10.1002/hep.21327/full
http://www.ncbi.nlm.nih.gov/pubmed/17006923?tool=bestpractice.com
In one longitudinal study of patients with fatty liver, fibrosis stage (but no other histologic feature) was associated with long-term outcomes.[155]Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015 Aug;149(2):389-97;e10.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516664
http://www.ncbi.nlm.nih.gov/pubmed/25935633?tool=bestpractice.com
Patients who have MASH progress to cirrhosis 9% to 20% of the time. Up to one third of these patients will die from complications from liver failure or require liver transplantation.[156]Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007 Feb;11(1):1-16;vii.
http://www.ncbi.nlm.nih.gov/pubmed/17544968?tool=bestpractice.com
With the epidemic number of individuals with MASLD, end-stage liver disease secondary to MASH cirrhosis is becoming a leading indication for liver transplant.[117]Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011 Oct;141(4):1249-53.
http://www.ncbi.nlm.nih.gov/pubmed/21726509?tool=bestpractice.com
Recurrent MASLD following liver transplant is a well-recognized phenomenon. The incidence of the development of post liver transplant steatosis ranges anywhere from 25% to 100%, and the incidence of MASH ranges from a low of 10% to as high as 37.5%.[157]Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001 Apr;7(4):363-73.
http://onlinelibrary.wiley.com/doi/10.1053/jlts.2001.23011/pdf
http://www.ncbi.nlm.nih.gov/pubmed/11303298?tool=bestpractice.com
Although recurrent MASH following liver transplantation is common, the development of allograft cirrhosis is rare, reported at less than 2% in one cohort study of more than 200 patients with a mean follow-up of 7 years.[158]Kakar S, Dugum M, Cabello R, et al. Incidence of Recurrent NASH-Related Allograft Cirrhosis. Dig Dis Sci. 2019 May;64(5):1356-63.
http://www.ncbi.nlm.nih.gov/pubmed/30560336?tool=bestpractice.com
Concurrent hepatitis C
Hepatic steatosis affects up to 80% of patients with chronic hepatitis C infection. Concurrent fatty liver disease with hepatitis C includes increased disease progression, elevated risk of primary liver cancer, and a decreased response to antiviral therapy.[159]Blonsky JJ, Harrison SA. Review article: nonalcoholic fatty liver disease and hepatitis C virus - partners in crime. Aliment Pharmacol Ther. 2008 May;27(10):855-65.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2008.03672.x/full
http://www.ncbi.nlm.nih.gov/pubmed/18315584?tool=bestpractice.com