NASH affects 15 million people in the U.S. and significantly increases the risk of cirrhosis, hepatocellular carcinoma and liver transplantation.
Non-alcoholic steatohepatitis (NASH) affects an estimated 15 million people in the U.S. Also known as metabolic dysfunction-associated steatohepatitis (MASH), NASH is the most advanced form of non-alcoholic fatty liver disease (NAFLD), a chronic condition which affects an estimated 30% to 40% of adult population of the U.S.[1] In NAFLD, fat accumulation or microvesicular steatosis exceeds 5% without an identifiable cause such as excessive alcohol consumption, toxins or virus.[2]
About one in seven patients with NAFLD (also called metabolic dysfunction-associated liver disease or MASLD) will progress to NASH, which is characterized by steatosis plus hepatocellular injury and inflammation, with or without fibrosis or scarring.[3]
NASH increases the risk of further liver complications with up to 50% of patients progressing to cirrhosis within a decade.[4] The progression of NAFLD to NASH increases the annual incidences of liver-specific mortality and hepatic carcinoma by more than an order of magnitude, rising from 0.77 and 0.44 per 1,000 person-year, respectively, to 11.77 and 5.29 per 1,000 person-year, respectively.[5] NASH is expected to become the most common reason for liver transplants and hepatocellular carcinoma in the U.S. in the next decade[6],[7]
Risk factors
The precise pathogenesis of NASH is not fully understood, but metabolism, gut microbiome, genetics appear to play a role.[8]
As the alternative names MASH and MASLD suggest, the full spectrum of NAFLD from simple steatosis to steatosis with fibrosis is closely related to metabolic dysregulation. Obesity is a major risk factor, in particular; 75% of obese individuals and 90% of those with morbid obesity have NAFLD, though the disease can affect those of normal weight or who are underweight as well.
In addition, diabetes increases the risk of NASH. A recent study found that 58% of randomly selected individuals with type 2 diabetes had NASH and 38% had NASH with advanced fibrosis.[9] Individuals with hypertension and hyperlipidemia are also much more likely to have NAFLD and NASH with fibrosis.
[1] Teng ML, Ng CH, Huang DQ, Chan KE, Tan DJ, Lim WH, Yang JD, Tan E, Muthiah MD. Global incidence and prevalence of nonalcoholic fatty liver disease. Clin Mol Hepatol. 2023 Feb;29(Suppl):S32-S42. doi: 10.3350/cmh.2022.0365. Epub 2022 Dec 14. PMID: 36517002; PMCID: PMC10029957.
[2] Westfall E, Jeske R, Bader AR. Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management. Am Fam Physician. 2020 Nov 15;102(10):603-612. PMID: 33179890.
[3] Westfall E, Jeske R, Bader AR. Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management. Am Fam Physician. 2020 Nov 15;102(10):603-612. PMID: 33179890.
[4] Sahu P, Chhabra P, Mehendale AM. A Comprehensive Review on Non-Alcoholic Fatty Liver Disease. Cureus. 2023 Dec 8;15(12):e50159. doi: 10.7759/cureus.50159. PMID: 38186528; PMCID: PMC10771633.
[5] Xia MF, Bian H, Gao X. NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment. Front Pharmacol. 2019 Aug 6;10:877. doi: 10.3389/fphar.2019.00877. PMID: 31447675; PMCID: PMC6691129.
[6] Nd AM. Non-Alcoholic Fatty Liver Disease, an Overview. Integr Med (Encinitas). 2019 Apr;18(2):42-49. PMID: 31341444; PMCID: PMC6601444.
[7] Sahu P, Chhabra P, Mehendale AM. A Comprehensive Review on Non-Alcoholic Fatty Liver Disease. Cureus. 2023 Dec 8;15(12):e50159. doi: 10.7759/cureus.50159. PMID: 38186528; PMCID: PMC10771633
[8] Sahu P, Chhabra P, Mehendale AM. A Comprehensive Review on Non-Alcoholic Fatty Liver Disease. Cureus. 2023 Dec 8;15(12):e50159. doi: 10.7759/cureus.50159. PMID: 38186528; PMCID: PMC10771633.
[9] Castera L, Laouenan C, Vallet-Pichard A, Vidal-Trécan T, Manchon P, Paradis V, Roulot D, Gault N, Boitard C, Terris B, Bihan H, Julla JB, Radu A, Poynard T, Brzustowsky A, Larger E, Czernichow S, Pol S, Bedossa P, Valla D, Gautier JF; QUID-NASH investigators. High Prevalence of NASH and Advanced Fibrosis in Type 2 Diabetes: A Prospective Study of 330 Outpatients Undergoing Liver Biopsies for Elevated ALT, Using a Low Threshold. Diabetes Care. 2023 Jul 1;46(7):1354-1362. doi: 10.2337/dc22-2048. PMID: 37043830.
