What is the workup for Non-Alcoholic Steatohepatitis (NASH)?

From the Guidelines

The Nash work up involves a comprehensive evaluation for non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD), and I recommend starting with basic laboratory tests including liver function tests (ALT, AST, GGT, alkaline phosphatase), complete blood count, lipid profile, fasting glucose, and HbA1c, as suggested by the most recent guidelines 1. Imaging should include an ultrasound of the liver as the initial screening tool, followed by transient elastography (FibroScan) to assess liver stiffness and steatosis. For patients with risk factors or abnormal initial tests, consider advanced imaging like MRI-PDFF or MR elastography. Serological fibrosis markers such as FIB-4 or NAFLD Fibrosis Score can help stratify risk. A liver biopsy remains the gold standard for definitive diagnosis and staging but is typically reserved for cases where the diagnosis is uncertain or to assess disease severity before treatment decisions. Management includes lifestyle modifications (weight loss of 7-10%, Mediterranean diet, regular exercise), control of metabolic comorbidities (diabetes, hypertension, dyslipidemia), and consideration of medications like vitamin E (800 IU daily) for non-diabetic patients with biopsy-proven NASH or pioglitazone for patients with type 2 diabetes and NASH, as supported by recent studies 1. Regular monitoring every 6-12 months with repeat liver function tests and non-invasive fibrosis assessment is essential to track disease progression. Key patient groups that should be screened for NAFLD include those with abnormal liver chemistry, type 2 diabetes, and patients older than 50 years who have hypertension and hyperlipidemia, as indicated by a recent survey of healthcare professionals 1. The use of non-invasive diagnostic tools, such as NAFLD fibrosis score or Fibrosis-4 Index, can help identify patients with a high likelihood of advanced fibrosis, and medications like pioglitazone and vitamin E may be considered for treatment, as suggested by recent guidelines 1. Overall, a comprehensive approach to the diagnosis and management of NASH is crucial to prevent disease progression and improve patient outcomes. Some key points to consider in the workup and management of NASH include:

• The importance of early diagnosis and treatment to prevent disease progression and complications
• The use of non-invasive diagnostic tools to assess liver stiffness and steatosis
• The role of lifestyle modifications and control of metabolic comorbidities in managing NASH
• The potential benefits and risks of medications like vitamin E and pioglitazone in the treatment of NASH
• The need for regular monitoring and follow-up to track disease progression and adjust treatment as needed.

From the Research

Diagnosis of NASH

• The diagnosis of Non-Alcoholic Steatohepatitis (NASH) requires the exclusion of alcohol abuse and hepatitis C as alternate causes of liver injury 2.
• The gold standard of diagnosis is liver biopsy 2, 3.
• Non-invasive tests and scoring systems exist to characterize NAFLD and NASH, but liver biopsy is the only accepted method for diagnosis of NASH 3.

Treatment of NASH

• Weight reduction, optimum blood glucose control, and elimination of medications implicated in causing the disorder are sensible first steps in treatment 2.
• Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss 3.
• Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss 3.
• In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect 3.
• Currently, no NASH-specific therapies are approved by the US Food and Drug Administration, but several drug candidates are in late-stage clinical trials 4.

Management of NASH

• Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients 5.
• The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis 5.
• Screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in NASH patients are necessary 5.
• The development of clinically relevant animal models and pharmacological treatments for NASH have been hampered by the limited understanding of the disease mechanism and a lack of sensitive, non-invasive diagnostic tools 6.

Prognosis of NASH

• An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US 3.
• The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD 3.
• NASH affects an estimated 3% to 6% of the US population, and its prevalence is increasing 3.