What is Nash (Non-Alcoholic Steatohepatitis)?

From the Guidelines

The management of nonalcoholic steatohepatitis (NASH) should prioritize a stepwise approach using non-invasive tests, such as the fibrosis-4 index (FIB-4), and lifestyle modification, including weight loss, dietary changes, and physical exercise, as recommended by the most recent guidelines 1.

Key Recommendations

• The clinical care pathway for NASH should involve a multidisciplinary approach, including primary care, gastroenterology, hepatology, obesity management, and endocrinology, to co-manage the hepatic manifestations of the disease and comorbid metabolic traits 1.
• Case-finding strategies for NASH with liver fibrosis should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity with additional metabolic risk factors 1.
• A stepwise approach using blood-based scores, such as FIB-4, and sequentially, imaging techniques, such as transient elastography, is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes 1.
• Lifestyle modification, including weight loss, dietary changes, physical exercise, and discouraging alcohol consumption, as well as optimal management of comorbidities, is advised for adults with NASH 1.
• Incretin-based therapies, such as semaglutide or tirzepatide, may be considered for type 2 diabetes or obesity management in individuals with NASH, if indicated 1.
• Bariatric surgery is an option in individuals with NASH and obesity 1.
• Resmetirom may be considered for adults with non-cirrhotic NASH and significant liver fibrosis (stage ≥2), if locally approved and dependent on the label 1.

From the Research

Definition and Prevalence of NASH

• Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) characterized by hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis 2.
• NASH affects an estimated 3% to 6% of the US population and is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome 3.
• The prevalence of NASH is increasing rapidly, and it is predicted to become the leading indication for liver transplants in the US 3.

Diagnosis and Treatment of NASH

• Liver biopsy is the only accepted method for diagnosis of NASH 3.
• Lifestyle modification, including dietary changes and exercise, is the mainstay of treatment for NASH, with the primary goal being weight loss 2, 3.
• Pharmacotherapies, such as vitamin E and pioglitazone, are recommended in patients with NASH, but concerns about their side effects remain 4.
• Bariatric surgery may be indicated in some cases to achieve and maintain the necessary degree of weight loss required for therapeutic effect 3.

Clinical Trials and Emerging Approaches

• The PIVENS trial was conducted to test the hypotheses that treatment with pioglitazone or vitamin E will lead to improvement in hepatic histology in non-diabetic adults with biopsy-proven NASH 5.
• Several agents targeting various vital molecules and pathways are in clinical trials for the treatment of NASH, but more studies are required to assess their long-term effects 4.
• Emerging approaches for NASH treatment include targeting downstream pathways of inflammation and fibrosis, as well as managing associated comorbidities such as diabetes, hypertension, and cardiovascular diseases 6.