What are the current treatment options for Non-Alcoholic Steatohepatitis (NASH)?

Current Treatment Options for Non-Alcoholic Steatohepatitis (NASH)

Lifestyle modifications remain the cornerstone of NASH treatment, with pharmacological options including vitamin E and pioglitazone for specific patient populations with biopsy-proven NASH. 1

First-Line Therapy: Lifestyle Modifications

Weight Loss

• Weight loss of 7-10% is the primary goal for overweight/obese patients with NASH, as it significantly improves liver histology, reduces steatosis, inflammation, and can reverse NASH 1, 2
• Even modest weight loss (3-5%) can improve hepatic steatosis, with more significant weight loss (5-10%) required to reduce hepatic inflammation 1, 3
• For lean individuals with NAFLD, a more modest weight loss target of 3-5% has been found to be beneficial 1

Dietary Recommendations

• Mediterranean diet is strongly recommended, characterized by reduced carbohydrate intake and increased monounsaturated and omega-3 fatty acid consumption 1, 2
• Specific dietary modifications include:
  • Limiting fructose and sugar-sweetened beverages 1
  • Replacing processed foods with unprocessed foods high in fiber 1
  • Replacing saturated fats with polyunsaturated and monounsaturated fats 1
  • Avoiding excess alcohol consumption 1

Physical Activity

• Both aerobic and resistance exercise are effective in reducing liver fat, even in the absence of significant weight loss 1, 4
• Regular physical activity provides metabolic benefits independent of weight loss 1, 4
• Any increase in physical activity over previous levels is beneficial compared to continued inactivity 2, 4

Pharmacological Treatment Options

For Non-Diabetic Patients with Biopsy-Proven NASH

• Vitamin E (800 IU/day) is recommended for non-diabetic adults with biopsy-confirmed NASH without cirrhosis 1
  • Improves steatosis through antioxidant properties 1, 2
  • Showed resolution of steatohepatitis in 36% of patients in the PIVENS trial 1
  • Potential concerns with long-term use include increased risk of all-cause mortality, hemorrhagic stroke, and prostate cancer 1, 5

For Patients with NASH and Type 2 Diabetes

• Pioglitazone (30 mg daily) is recommended for patients with biopsy-confirmed NASH with or without diabetes 1
  • Improves all histological features of NASH except fibrosis 1, 2
  • Led to resolution of steatohepatitis in 47% of patients compared to 21% in placebo group in the PIVENS trial 1
  • Side effects include weight gain, peripheral edema, heart failure, and increased fracture risk in women 1, 5

Medications Not Recommended

• Metformin is not recommended specifically for NASH treatment despite its benefits in diabetes management 1, 5
  • Has no significant effect on liver histology in patients with NASH 5
  • May be used in NASH patients who also have diabetes, but not for the liver disease itself 5

Treatment Algorithm Based on Disease Stage

NAFL (Simple Steatosis) or NASH with Minimal Fibrosis (F0-F1)

• Focus on lifestyle modifications only 2, 6
• No specific liver-directed pharmacotherapy recommended 2
• Follow-up with non-invasive testing for fibrosis every 2-3 years 1

NASH with Significant Fibrosis (F2-F3)

• Intensive lifestyle modifications as primary therapy 1, 2
• Consider pharmacotherapy:
  • Vitamin E (800 IU/day) for non-diabetic patients 1
  • Pioglitazone for diabetic patients 1
• More frequent monitoring with non-invasive tests 1

NASH with Cirrhosis (F4)

• Lifestyle modifications with careful monitoring 2
• Limited evidence for pharmacotherapy in this group 2
• Hepatocellular carcinoma surveillance with ultrasound every 6 months 1, 2
• Evaluation for liver transplantation if signs of decompensation develop 1

Bariatric Surgery

• Consider for obese patients who fail to achieve adequate weight loss through lifestyle modifications 7, 8
• Has been shown to improve liver histology including fibrosis secondary to NASH 7
• Additional benefits include improvement or resolution of type 2 diabetes, dyslipidemia, and hypertension 7

Emerging Therapies

• GLP-1 receptor agonists and SGLT2 inhibitors show promise but require further investigation for lean NAFLD 1
• Several agents targeting various pathways are in clinical trials, but none are currently FDA-approved for NASH 1, 6

Key Pitfalls to Avoid

• Relying solely on pharmacotherapy without implementing lifestyle changes 1, 3
• Using metformin specifically for NASH treatment 5
• Failing to screen for advanced fibrosis, which requires more intensive monitoring and management 1
• Neglecting cardiovascular risk assessment and management, as cardiovascular disease is a leading cause of mortality in NASH patients 1