Approach to Abnormal LFTs
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Approach to Abnormal Liver Function TestsSobha Koduru Sameer Gunukula Castro Bali Dr Ellen P Rich
Relevance of the topic
Abnormal LFTs are frequently detected as many routine screening test panels include LFTs. According to the American Gastroenterological Association (AGA), 1- 4 % of the asymptomatic 1population may have elevated serum liver chemistries. The clinical profile may range from asymptomatic to florid manifestations of liver disease. A diagnosis can be established noninvasively in a vast majority of patients. Source: AGA
Familiarize with common liver function test abnormalities Identify the common patterns of liver function test abnormalities Discuss differential diagnoses and develop diagnostic approach based on the pretest probabilities.
TEST AST(10 to 35 IU/L[ ) IU/L[ ALT(9 to 40 IU/L )
ALP(30 to 120 IU/L) GGT(0 to 42 IU/L ) 5 NT( 2-16 IU/L) 2BILIRUBIN (0.21.2 mg/dL ) (0.2 ALBUMIN (3.5 to 5.3 g/dL ) PROTHROMBIN(INR)
SYNTHESIS AND METABOLISM
Approach History:- The most important part in
evaluation of a patient with abnormal LFTs Exposure to any chemicals Use of any medications The duration of abnormal LFTs The presence of accompanying symptoms e.g jaundice, arthralgia, Wt loss, fever, pruritus
Physical examination: - ?finding suggestive CLD
Patterns of abnormal LFTs
Chronic mild elevation of transaminases Isolated Hyperbilirubinemia Elevated alkaline phosphatase Simultaneous elevation of several LFTs
Case 1A 65-year-old Caucasian woman is seen for a first visit. 65-yearIn her record, it is noted that she has had a history of hypertension and a 15-year history of diabetes mellitus 15without end-organ damage. This was initially controlled endwith oral agents; she is now on insulin. She also received a single unit of blood in Puerto Rico 25 years ago during an abdominal hysterectomy for a bleeding fibroid uterus. Her review of systems is unremarkable, and her examination is normal. She has a BMI of 32. Laboratory examination shows normal electrolytes, BUN, and creatinine. Glucose is 123 mg/dl (65-110). ALT (SGPT) (65is 109 IU/L (9-40) and AST (SGOT) is 83 (10-35). Alkaline (9(10phosphatase is 129 IU/L (43-122). Bilirubins are normal. (43-
Does it merit further testing ?
Patterns of abnormal LFTs Chronic
mild elevation of transaminasesIsolated Hyperbilirubinemia Elevated alkaline phosphatase Simultaneous elevation of several LFTs
Chronic mild elevation of transaminases
Defined as less than four times the upper limit of normal of one or both the aminotransferases for six months or greater duration.
Differential diagnoses to consider
Medications (Common causes include NSAIDS, antibiotics, statins, antiepileptic drugs, and antituberculous drugs) Alcohol abuse Hepatitis B, C Hereditary hemochromatosis Hepatic steatosis Muscle disorders Thyroid disease Celiac disease Autoimmune hepatitis Wilson disease Alpha 1 antitrypsin deficiency
Step 1 Review possible link to medications, herbal therapies or recreational drugs. An asymptomatic elevation of liver function tests does not necessitate the discontinuation of the medication; a risk-benefit assessment must first take place. riskScreen for alcohol abuse (AST/ALT ratio >2:1) Obtain serology for hepatitis B and C (HBsAg, HBsAb, HBcAb, HCV Ab) Evaluate for fatty liver (AST/ALT usually < 1, obtain a RUQ ultrasound) Hemochromatosis screening test being transferrin saturation (fasting serum iron/iron binding capacity over 45%). The frequency of heterozygotes is about 10% in Caucasian populations in the U.S and western Europe.
Step 2: Exclude muscle disorders (obtain creatinine kinase or aldolase) Obtain thyroid function tests Consider celiac disease (especially in patients with a h/o diarrhea or unexplained iron deficiency - serum antiendomysial IgA or anti tissue transglutaminase IgA antibodies are reasonable screening tests) Non hepatic causes of AST elevation Myocardial Infarction, severe arrythmias, severe angina, skeletal muscle necrosis and renal necrosis.
Step 3:- Consider less common causes of liver disease 3:Autoimmune hepatitis particularly in women and those with a history of other autoimmune disorders (check serum proteinelectrophoresis, obtain ANA and ASMA) Consider Wilson's disease in those 6 months Liver enzymes >2x ULN Liver biopsy confirms active disease. HBSAg + ve, HBV DNA and HBeAg -ve suggests carrier state of hepatitis B which is a non-replicative state. nonThe presence of a carrier state does not explain elevated aminotransferases, and another cause needs to be sought.
Chronic Hepatitis C
HCV antibody +, With detectable HCV RNA Liver enzymes often normal to < 2X ULN 30% have persistently normal ALT and rarely progress. Genotype important in treatment and prognosis About 16% of patients with hepatitis C may have normal liver tests despite having histological damage. So a liver biopsy would be accurate to demonstrate underlying histological abnormalities than liver tests.
Laboratory Clues to Alcoholic Liver Disease (ALD)
AST more than twice ALT >90% predictive when AST 2X >ALT
The AST rarely exceeds 300 U/LGGT disease >2X highly predictive of alcoholic liver
Poor prognosis factors for ALD
Total and direct Bilirubin Albumin PT Childs Pugh grade C, MELD score >10
NonNon-alcoholic Fatty Liver Disease (NAFLD) & NonNon-alcoholic Steatohepatitis (NASH)
Incidence with several known risk factors NASH more common in women Obesity Hyperlipidemia Type 2 diabetes Most common cause of AST & ALT