Elevated Liver Enzymes Hepatitis NAFLD 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,
Hepatitis: - 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)
NAFLDEpidemiology:
- 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)
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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
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
Focal Liver LesionCase Based Learning 48 yo M is seen in the clinic. Labs include the following.
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.
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