Makindo Medical Notes

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

• NICE Guideline [NG49] on NAFLD: Assessment and Management, 2016
• Review on Nonalcoholic Fatty Liver Disease
• Current and Emerging Therapies for NASH