Non-alcoholic Steatohepatitis

Question 1

Define NASH

Answer 1

inflammation of the liver, accompanied by hepatocyte steatosis, that cannot be attributed to any other cause (i.e. not alcoholic, not autoimmune and not viral). It is a subset of non-alcoholic fatty liver disease (NAFLD)

Question 2

What are the stages of NASH?

Answer 2

1. Steatosis –fat deposition in the liver
2. Steatohepatitis
3. Fibrosis
4. Cirrhosis

Question 3

What are the causes/risk factors of NASH?

Answer 3

• NASH most commonly occurs due to insulin resistance as part of the metabolic syndrome.
• Age
• Obesity
• T2DM and Insulin Resistance
• Dyslipidaemia
• Hypertension
• Metabolic Syndrome, 3 of: Obesity, Hypertension, Diabetes/ IR, Hypertriglyceridaemia and dyslipidaemia

Question 4

What are the symptoms of NASH?

Answer 4

• Non-alcoholic
• History of components of the metabolic syndrome
• Usually asymptomatic, even at an advanced stage of the disease; incidental findings.
• Non-specific symptoms: Fever, fatigue malaise, RUQ pain and jaundice.
• May present with upper GI bleeds due to oesophageal varices secondary to portal hypertension

Question 5

What are the signs of NASH?

Answer 5

• Early on, there will be no signs on examination.
• Later, the patient will develop the classical stigmata of chronic liver disease:
- Asterixis, Ascites, Ankle Oedema, Atrophy of testicles
- Bruises and Petechiae
- Clubbing, Colour change in the nails (Leukonychia), Caput Medusae
- Dupuyten’s Contractures
- Erythema (Palmar), Encephalopathy
- Foetor hepaticus
- Gynaecomastia and hair loss
- Hepatomegaly
- Increase size of parotids, Itching/pruritus due to BR deposition in the skin.
- Jaundice; Spider Naevi and Striae

Question 6

What investigations are carried out for NASH?

Answer 6

• FBC - macrocytic (High MCV) Anaemia, Leucocytosis and Thrombocytopaenia.
• LFTs - elevated ALT and AST, AST: ALT Ratio < 1, raised GGT –very sensitive, high BR, low Albumin
• Lipid Panel - elevated total cholesterol, LDL, triglyceride, and low HDL.
• Fasting Insulin - elevated (indicates IR).
• Clotting Screen - PT and INR: Prolonged
• Serum Ammonia - elevated ammonia level does not correlate with severity of hepatic encephalopathy alone. Therefore, its routine use in diagnosis of hepatic encephalopathy is not always necessary.
• Ascitic Fluid Tap - if ascites, to screen for infection –SBP: Subacute Bacterial Peritonitis.
• Liver USS - may show hepatomegaly, fatty liver, liver cirrhosis. May show masses and malignancies.
• OGD - shows upper GI bleeding and oesophageal varices.
• Liver Biopsy - percutaneous or transjugular (in the presence of coagulopathy) may be helpful to distinguish from other causes of hepatitis. Biopsy shows: steatosis, inflammation-neutrophil infiltrate, ballooning hepatocytes, Mallory hyaline bodies, pericellular fibrosis.
• EEG - for slow-wave activity indicative of encephalopathy.
• CT/ MRI - may show hepatomegaly, splenomegaly, ascites, and portal vein engorgement.
• Liver Elastography -
measures liver stiffness and indicates extent of damage and presence of cirrhosis.
• Other Investigations (to rule out other causes of liver disease):
- Viral serology –Viral Hepatitis.
- Caeruloplasmin and urinary copper –Wilson’s disease
- Fe, Ferritin and transferrin saturation –Haemochromatosis
- α1-Antitrypsin –α1-Antitrypsin Deficiency
- Antimitochondrial antibodies –PBC.
- Autoantibodies for AIH.

Question 7

What is the management for NASH?

Answer 7

Conservative: 
• Weight loss
• diabetes control
• caloric restriction diet
• physical activity

Medical:
• Orlistat
• Insulin sensitisers and drugs for T2DM
• Statins for dyslipidaemia

Surgical:
• Liver transplantation for end-stage liver disease. NASH is projected to be the primary indication for liver transplantation worldwide, superseding Hepatitis C.
• Transjugular Intrahepatic Portosystemic Shunt
• Bariatric surgery for insulin resistance and obesity

Monitoring:
• If cirrhosis is present, then a liver USS twice/ year to exclude HCC.
• Monitor for complications including cardiovascular disease risks and diabetic microvascular complications

Question 8

What are the complications of NASH?

Answer 8

• Decompensated liver disease: encephalopathy, jaundice and ascites
• Hepatorenal syndrome: Renal failure secondary to liver disease
• Cirrhosis
• Liver failure
• HCC
• Increases the risk of DM, MI, stroke