• ALT > 3 times upper limit of normal and a T Bi > 2 times upper limit : combined test is used to define clinically significant abnormalities on liver tests, with further verification through the analysis of additional clinical data NEJM 2006.  

References:
Ordering and interpreting hepatitis B serology BMJ 2014
Hepatitis (Acute / Chronic)
Non-alcoholic fatty liver disease BMJ 2014
Bilirubin-Induced Neurologic Damage — Mechanisms and mnt. approaches NEJM 2013

Autoimmune hepatitis – Update 2015 Journal of Hepatology 2015

Autoimmune hepatitis – Update 2015 Journal of Hepatology 2015

Autoimmune hepatitis – Update 2015 Journal of Hepatology 2015

Autoimmune hepatitis – Update 2015 Journal of Hepatology 2015

Drug-Related Hepatotoxicity NEJM 2006
Gilbert’s syndrome BMJ 2011

Epidemiology:

• 70 % of Type 2 DM; 20% of General Population

Pathogenies

• Cytokines involved are: TNF, IL 6, MCP -1 
• Insulin resistance
• Dyslipidemia (increased VLDL, LDL as disease severity progresses)
• ..
• ..

Diagnosis

• No or modest amount of alcohol (daily intake <20 g (2.5 units) in women and <30 g (3.75 units) in men) 
• Diagnosis of exclusion 

DDx:

• Alcoholic FLD (increased HDL, and TG; TG level can vary)
• Drugs (Amiodarone, Diltiazem, Steroids, Synthetic Estrogen, Tamoxifen, ART,)
• Refeeding Syndrome and TPN 
• Severe weight loss after jejunojejunal or gastric bypass
• Lipodystrophy

Stage

• First: Hepatic Steatosis (Fat content exceeds 5 %) (20 % of general population)
• Is a risk factor for DM2, and NASH
• DDx: 
• Work up: 
• Identify the patient with high risk for progression or NAFLD severity
• NAFLD Fibrosis Score
• FIB-4 Score (more simpler than NAFLD Fibrosis score)
• BARD Score (AST : ALT > 0.8 is advanced stage)
• Transient Elsastography (using Fibroscan) 
• Enhanced liver fibrosis panel 
• Second: NASH (3-5 % of general population)
• Much higher risk of disease progression
• Third / Final : Cirrhosis (1% of general population) 

Screening

• No need for NAFLD (lack of definitive interventions)
• Once NAFLD is suspected, screen for 
• DM (A1C)
• Dyslipidemia

Labs:

• Inititally ALT > AST; With further progression to NASH and Hepatic Fibrosis, AST can be > ALT 
• AST, ALT typically <10 times upper limit o normal
• Anti-smooth muscle and ANA may be weekly positive  
• HDL is usually low

Imaging

• USG has poor sensitivity (many people who have biopsy proven hepatic steatosis has normal USG) and cannot distinguish Hepatic Steatosis from NASH
• If Phenotypically, Biochemically, it is suggestive of NAFLD, then need of USG is questionable given its limitations, and not change in management

Treatment

• Life style intervention (Systemic Rreview of 23 literature favors this)
• Diet and Exercise 
• >7 % weight loss is associated with significant improvement in early stage of the disease (not fibrosis) 
• Continue statin if on it for CV risks 
• PiVEN Study (Pioglitazone, Vit E)
• Vitamin E had benefit in fibrosis score, but has increased all cause mortality and increased prostrate cancer 

Need of Biopsy

• Very limited role
• If performed in advanced stage NAFLD, benefit is in guiding HCC screening, and Variceal Screening
• 41-56 % of HCC occurs in the absence of Cirrhosis in a patient with Hepatic Steatosis / NASH
• Hepatic Steatosis: 3-4 % progression to cirrhosis in 10 yr
• NASH: 10 or more % progression to cirrhosis 

Causes of Death

• Malignancy 27 % (breast cancer, colon cancer)
• Ischemic Heart Disease 25 %
• Liver Disease 13 %

Reference

• Non-alcoholic fatty liver disease BMJ 2014

• Cholestatic Pattern 
• Infiltrative Pattern
• Mixed pattern is possible, but one can expect slightly increased AST/ALT 

• Alcohol
• Hep B, Hep C
• PBC, PSC
• Sarcoidiosis
• Infiltrative. Amylodiosis, Lymphoma
• Malignancy - HCC, Metastatic