Related Subjects:
| Chronic Liver Disease
| Cirrhosis
| Alkaline Phosphatase (ALP)
| Liver Function Tests
| Ascites Assessment and Management
| Budd-Chiari Syndrome
| Autoimmune Hepatitis
| Primary Biliary Cirrhosis
| Primary Sclerosing Cholangitis
| Wilson Disease
| Hereditary Haemochromatosis
| Alpha-1 Antitrypsin (AAT) Deficiency
| Nonalcoholic Steatohepatitis (NASH)
| Spontaneous Bacterial Peritonitis
| Alcoholism and Alcoholic Liver Disease
| Liver Transplantation
About
- Non-Alcoholic Steatohepatitis (NASH) is a progressive liver condition characterized by inflammation, hepatocyte damage, and fibrosis in individuals who consume minimal or no alcohol (<40g/week).
- NASH is part of the spectrum of Non-Alcoholic Fatty Liver Disease (NAFLD) , which ranges from simple fatty liver (steatosis) to more severe forms like NASH, and can lead to cirrhosis, liver failure, or hepatocellular carcinoma (HCC).
- NASH mirrors the histological features of alcoholic liver disease without alcohol use, making it a major cause of cryptogenic cirrhosis.
Aetiology
- Risk Factors: Metabolic syndrome components such as obesity (BMI > 25), type 2 diabetes mellitus (T2DM), dyslipidemia (elevated triglycerides, low HDL), hypertension (HTN), and insulin resistance.
- Genetic factors: Certain gene polymorphisms (such as PNPLA3 and TM6SF2) have been associated with a higher risk of developing NASH.
- Secondary causes include medications like corticosteroids, amiodarone, and tamoxifen, as well as rapid weight loss or malnutrition.
Clinical Features
- Many patients with NASH are asymptomatic and diagnosed incidentally during routine blood tests or imaging.
- When symptomatic, common presentations include fatigue , malaise, and right upper quadrant discomfort .
- Advanced disease may present with signs of cirrhosis, such as jaundice, ascites, hepatomegaly, or splenomegaly.
- Approximately 20-25% of patients with NASH will develop cirrhosis over time, increasing the risk of liver-related morbidity and mortality.
Investigations
- Liver function tests (LFTs): Elevated ALT and AST levels (often with ALT > AST), but these may be normal in some cases.
- Liver biopsy: The gold standard for diagnosis, showing features like steatosis, lobular inflammation, hepatocyte ballooning, and pericellular fibrosis.
- Imaging studies: Ultrasound, CT, or MRI can detect fatty infiltration but cannot reliably differentiate between simple steatosis and NASH.
- Non-invasive fibrosis markers: Tests like FibroScan (transient elastography) and serum biomarkers (e.g., ELF test) are increasingly used to assess liver fibrosis.
- Exclusion of other causes: Viral hepatitis (hepatitis B and C), autoimmune liver diseases, and alcoholic liver disease should be excluded.
Management
- Lifestyle modification: The cornerstone of management is weight loss through diet and exercise. A weight loss of 7-10% of body weight is recommended for reducing liver fat and improving inflammation.
- Pharmacotherapy: While no drug is currently approved specifically for NASH, treatments targeting underlying conditions (e.g., insulin resistance, dyslipidemia) are used:
- Pioglitazone: Shown to reduce inflammation and fibrosis, especially in diabetic patients.
- Vitamin E: May be used in non-diabetic patients with NASH to improve liver histology.
- Metformin: Improves insulin sensitivity but has limited effects on liver histology in NASH.
- Statins: Used to manage dyslipidemia and reduce cardiovascular risk but do not treat NASH directly.
- Emerging therapies: GLP-1 receptor agonists (e.g., liraglutide), SGLT2 inhibitors , and FXR agonists are under investigation for treating NASH.
- Management of comorbidities: Control of hypertension, diabetes, and dyslipidemia is critical in reducing the risk of cardiovascular disease, the leading cause of death in patients with NASH.
- Liver transplantation: Considered in patients with end-stage liver disease (cirrhosis) due to NASH, especially those with hepatocellular carcinoma.
Prognosis
- While NAFL may remain stable for many years, NASH carries a significant risk of progression to cirrhosis and liver failure.
- NASH-related cirrhosis is a major cause of liver transplantation, and patients with cirrhosis have an increased risk of developing hepatocellular carcinoma (HCC).
- Cardiovascular disease is the leading cause of death in patients with NAFLD and NASH, making aggressive management of cardiovascular risk factors critical.
References