Hepatitis / Acute Liver Failure / Elevated Liver Enzy / Focal Liver Lesion

Elevated Liver Enzymes
Liver Failure: Hyperacute / Acute / Subacute 2/2 - Assess for complication
Focal Liver Lesion
Case Based Learning 

Elevated Liver Enzymes

Suspecting Acute Hepatitis: Tests to order are:
  • hepatitis A IgM antibody assay, 
  • hepatitis B surface antigen and core IgM antibody assay, 
  • hepatitis C viral RNA test, and, 

depending on the circumstances other tests to consider are 

  • hepatitis E IgM antibody assay.  
  • hepatitis D tests,
  • Epstein-Barr virus (EBV), and 
  • cytomegalovirus (CMV)  
  • Ceruloplasmin (initial screening test for Wilson’s disease). 
  • AIH tests, ANA, measurement of specific immunoglobulins.
Evaluation of isolated mild  elevation of serum aminotransferases Up-to-date
Evaluation of abnormal Liver-enzymes in asymptomatic patients NEJM 2000

Elevated ALP: Interpreting an isolated raised serum ALP level in an asymptomatic pt   BMJ 2013 

  • 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 
a.     Hepatocellular Pattern:
b.     Cholestasis Pattern:
c.      Mixed Pattern:
d.     Elevated ALP: Repeat ALP à Persistent àLiver  (GGT, 5NT, Fractionation of ALP) vs Bone Marrow (Paget’s)

  • 70 % of Type 2 DM; 20% of General Population
  • Cytokines involved are: TNF, IL 6, MCP -1 
  • Insulin resistance
  • Dyslipidemia (increased VLDL, LDL as disease severity progresses)
  • ..
  • ..
  • 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 
  • 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
  • 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) 
  • No need for NAFLD (lack of definitive interventions)
  • Once NAFLD is suspected, screen for 
    • DM (A1C)
    • Dyslipidemia
  • 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
  • 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
  • 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 %

Liver Failure: Hyperacute / Acute / Subacute 2/2 - Assess for complication
Neurologic Complications (Intracranial Hypertension, NH3, Risk of Infection)
Cardiorespiratory Status (Risk of Infection, Relative adrenal Insufficiency, MI, ALI/ARDS, Hypoperfusion)
Renal Dysfunction
Metabolic changes and Nutritional Support
Prognostic Evaluations

Modified West Haven Criteria for grading of encephalopathy with comparable Glasgow Coma Scale (GCS) in Acute Liver Failure. NEJM 2013

Acute-on-chronic liver failure Lancet 2015

Hepatitis / Hepatic Failure:
Case 37-2013: A 41-Year-Old Woman with Malaise and Chest and Abdominal Pain (Acute Hepatitis / Acute Hepatitis C)
Case 10-2011 (Hemophagocytic Lymphocytosis)

Focal Liver Lesion
Case Based Learning 
48 yo M is seen in the clinic. Labs include the following. 

What are the non-hepatic causes of increase in ALP? 

But, our patient has increase in AST and ALT as well. It is likely liver in origin. GGT was done , and was increased. So, what is the pattern of hepatitis in our patient? 

There are 4 pattern of hepatitis. 
Approach To A Patient With Elevated Serum Alkaline Phosphatase Clin Liver Dis. 2012

So, based on this, our patient can have either of the following. 
  • Cholestatic Pattern 
  • Infiltrative Pattern
  • Mixed pattern is possible, but one can expect slightly increased AST/ALT 
What the causes of Cholestatic Pattern of Liver Injury? 2 Types: See the table here

How do you differentiate between the two?
USG abdomen or MRCP to look for CBD dilatation. Our patient does not have CBD dilatation. 

So, it has to be the intrahepatic cholestasis? What are the common causes. 
  • Alcohol
  • Hep B, Hep C
  • PBC, PSC
  • Sarcoidiosis
  • Infiltrative. Amylodiosis, Lymphoma
  • Malignancy - HCC, Metastatic
Our patient does not have hx of Alcohol, Hep B and Hep C test are normal. 

Liver biopsy is done to assess for the other cause.