Evaluation of Abnormal Liver Function Tests

Overview

• Background

• Elevated Transaminases

• Isolated Hyperbilirubinaemia

• Elevated Alkaline phosphatase

• Mixed Picture

• Case History

Background

• Liver function tests ordered routinely• 1-4% of asymptomatic patients have

abnormal values• Population based survey-8.9% raised ALT• OBESITY• Serious underlying disease uncommon• Diagnosis often reached non invasively• No consensus on cost effective approach

HISTORY

• Duration of abnormaL LFT• Symptoms- Jaundice, arthralgia, pain,

pruritus, weight loss• Medication (Herbal)• Travel History• Transfusion• IV drug abuse• ALCOHOL

EXAMINATION

• Stigmata of chronic liver disease

• Lympadenopathy

• Periumbilical nodule

• Palpable mass

Transaminases

• May not be elevated in chronic liver disease– HCV– Cirrhosis

• Minimal ALT elevations (<1.5 X normal)– Race/Gender– Obesity – Muscle injury

Elevation in Serum Transaminases

STEP 1

• Medications, herbal treatment, drugs

• Screen for alcohol abuse (AST/ALT>2:1)

• Obtain serology for Hepatitis B & C

• Screen for Haemochromatosis (TIBC>45%)

• USG (?Fatty Liver)

Elevation in Serum Transaminases

STEP 2

• Consider Autoimmune liver disease

• Wilson’s Disease (<40)

• Alpha 1 antitrypsin Deficiency (Emphysema)

Elevation in Serum Transaminases

STEP 3

• Exclude muscle disorder (CK)

• Check TFT

• ?Coeliac (Fe def)

• Adrenal insufficiency

STEP 4

• Liver Biopsy ? When

Elevated AST & ALT, <4X normal

Hx & physical; stop hepatotoxic meds

LFTs, PT, albumin, CBC, Hep A/B/C, Fe,

TIBC, Ferritin

Positive serologyNegative serologyNegative serology,

asymptomatic

Serologies:HAV IgMHBsAgHBcIgMHCV Ab or RNA

Stop EtOH & meds; wt loss; glucose control

Repeat LFTs

ObservationUltrasound, ANA, smooth muscle Ab, ceruloplasmin,

antitrypsin, gliadin & endomysial Ab

Negative Serology- Asymptomatic

Liver biopsy

Abnormal Normal

6 months

☺

Consider ultrasound, ANA, smooth muscle Ab, ceruloplasmin,

antitrypsin

Liver biopsy

Negative Serology- Clinical Signs/Symptoms of Liver Disease

Abnormal

☺

Isolated Hyperbilirubinemia

• Product of hemoglobin breakdown

Unconjugated (indirect)- insoluble• Haemolysis (Reticulocyte count)• Gilbert’s syndrome (3-7% population)

Alkaline Phosphatase

• Produced by biliary epithelial cells– Non-specific to liver: bone, intestine, placenta

• Elevations– Biliary duct obstruction– Primary biliary cirrhosis– Primary sclerosing cholangitis– Infiltrative liver disease- ie sarcoid, lymphoma– Hepatitis/cirrhosis– Medications

Elevated Serum alkaline phoaphatase

Rule out physiological causePregnancy, post pandrial

DETERMINE THE SOURCEGGT

Normal Increased

Bone origin Hepatobiliary origin

ALP Hepatobiliary origin

Check AMAUSG

AMA PositiveUSG abnormal parenchyma

Dilated bile ductsAMA negativeUSG -Normal

LIVER BIOPSYERCPMRCP

Assess degree of ALP elevation

LIVER BIOPSYMRCP

MIXED PICTURE

Hepatocellular pattern with Jaundice

• Alcoholic hepatitis

• Viral Hepatitis (A &E)

• Toxic hepatitis (Paracetamol, Wild mushroom)

• Autoimmune

• Wilson’s

MIXED PICTURE

CHOLESTATIC PICTURE• USGExtrahepatic• Choledocholithiasis• Pancreatic cancer• Cholangiocarcinoma• PSCIntrahepatic(Drug induced,PBC,PSC,Pregnancy)

Other Liver Labs

• Albumin– decreased by trauma, inflammatory

conditions, malnutrition• Prothrombin time (PT)

-no change until liver loses 80% capacity• Ammonia

– No correlation between brain & serum values– Related to encephalopathy

Summary

• Algorithms based on poor quality or absence of evidence

• Most asymptomatic patients can safely be followed for a period of time to see if abnormalities resolve

• If lab abnormalities persist be thoughtful with ordering

Nonalcoholic steatohepatitis

• No significant alcohol but liver biopsy similar to alcoholic steatohepatitis

• No hepatitis B or C

• Central obesity, type 2 DM, Dyslipidemia- Metabolic syndrome

• Men – 20-40% of population

• ?Insulin resistance /?oxidative injury

Nonalcoholic steatohepatitis

• Stable condition- compared to ALD

• Asymptomatic- ?fatigue

• Role of liver biopsy - prognosis

• 8-26% – histological progression- linked with obesity, liver biopsy –balloon degeneration, Mallory hyaline

• Cirrhosis – 3-15%( >45,0besity,DM)

Treatment

• Weight reduction- gradual

• Diabetic and Lipid control

• Vitamin E & Vitamin C

• Metformin

• Rosiglitazone

• Pentoxifylline

Mallory bodies

NASH