Evaluation of liver enzyme elevation.pptx

Liver enzymes are SGPT, SGOT, ALP, GGT. These are increase with various disease condition. Enzymes increase also indicate abnormal liver function. Almost all disease affect liver increase liver enzymes. Enzymes may be symptomatic may be asymptomatic. There is different pattern. Hepatitic pattern which involve SGPT, SGOT predominantly. Obstructive pattern involve ALP and GGT predominantly. Mixed pattern also present where both enzyme elevate. Enzymes also increase with variable degree like mild, moderate and severe. Severe elevation occur various disease including acute viral hepatitis, drug induced hepatitis, Wilson's hepatitis, autoimmune hepatitis, alcoholic hepatitis, acute buddchiari syndrome etc. moderate elevation occur in chronic hepatitis B, chronic hepatitis C, Hemochromatosis, NASH, alcoholic hepatitis, alpha antitrypsin deficiency and other metabolic disease. Many viral infection like herpes, CMV also raise liver enzyme. Acute liver failure also associate with raise liver enzymes but not indicate liver disease severity. Approach to elevation of liver enzyme include history, clinical examination, drug history, disease history, pattern of elevation, degree of enzymes elevation, important investigation. Another condition named isolated bilirubin elevation. It includes Gilbert syndrome, crigler Nagar syndrome, Dublin Johnson, rotor syndrome and some drug related causes.

1. Welcome To Journal Presentation Dr. Md. Ashiqur Rahman Phase-B resident Dept. of Gastroenterology

2. Elevated Liver Enzymes in Asymptomatic Patients – What Should I Do? Author : Mazyar Malakouti , Archish Kataria , Sayed K. Ali and Steven Schenker Published : Journal of Clinical and Translational Hepatology Year : 2017 Type : Review Article

3. Introduction Evaluation of abnormal liver enzymes level in asymptomatic individuals is challenging. Serious investigations to find the causes may lead to high procedural risk and expenses. Failure to investigate early may result in life threatening diagnosis.

4. Approx. 1% to 9% asymptomatic patients have elevated liver enzymes when screened routinely. In a US from 1999 to 2002, 8 .9 % of the study population show elevated alanine aminotransferase level.

5. Elevated ALT or AST above ULN ( 30 IU/L for men and 20 IU/L for women ) without any identifiable risk factors should be evaluated. Physiological causes of raise Pregnency ( ALP) Vigorous Exercise ( ALT,AST)

6. Approach Detail History Clinical Examinations Relevants Investigations Blood tests Liver Imaging Liver Histology

7. I f Still Persist

8. Hepatocellular (Elevated aminotransferases )

9. History 1. Patient age and ethnicity; 2 . Presence of signs and symptoms of chronic liver disease 3 . Risk factors for viral hepatitis 4 . Presence of comorbid conditions like diabetes, obesity, hyperlipidemia , neurologic manifestations in Wilson’s disease, emphysema in alpha-1-antitrypsin deficiency;

10. 5. History of alcohol consumption, medication use, and toxin exposure 6. Family history of genetic conditions such as hemochromatosis and WD 7 . History of chronic diarrhea, indicating extrahepatic causes like celiac sprue , thyroid disorders, IBD etc . 8 . Presence of signs and symptoms of heart failure, 9 . History of other autoimmune disorders

11. Physical Examination Stigmata of acute and chronic liver disease Hemochomatosis and WD Arthritis Acne Skin color change K-F ring Clubbing CCF Raised JVP Hepatomegaly Lung basal cracles

12. Diagnostic Algorithm

13. Alcohol-related hepatic injury First indicator is AST:ALT >2:1 GGT is sensitive, but non-specific GGT >2x ULN with AST:ALT >2:1 strongly indicate ARHI ALT may be normal Raised bilirubin in severe acute alcoholic hepatitis Risk of raised transaminase more in overweight or obesity

14. Viral Hepatitis Early and empiric testing of HBV and HCV even in absence of risk factors for pts HEV considered in endemic area Most chronic patient ALT,AST <100 ALT:AST >1 AST:ALT >1 indicate progress to cirrhosis (79%)

15. NAFLD Simple steatosis to NASH to cirrhosis High risk group (T2DM, morbid obesity) ALT >AST making AST:ALT<1 Reversal of ratio that means AST:ALT>1 indicate advanced fibrosis GGT upto 3x ULN in 50% Bilirubin , Albumin preserved in early stage Leucopenia, thrombocytopenia – suspicion of cirrhosis or occult portal HTN Biopsy – Gold standard Histology- Fatty infiltration, periportal fibrosis, inflamation and hepatic necrosis

16. Hemochromatosis Considerderd in men in north European descent Screening Iron level TSAT + ve screening test – TSAT >45% Liver biopsy (Gold standard) – Hepatic iron >1.9 indicate HH Genetic test has lack of sensitivity Ferritin <1000µg/L, normal AST, No hepatomegaly – No cirrhosis

17. WD Raised liver enzymes without clinical symptoms Initial screening is s.ceruloplasmin (85%) Slit-lamp exam for K-F ring is clinical clue 24 urinary cu >100µg/day suggestive Cu conc. >250µg/g dry liver wt on biopsy Genetic test is not useful to make Dx

18. AIH Young to middle age women with concominent autoimmuno disease 80% pt have hyperGglobinemia IgG >2x suggestive <40 years, ANA/ASMA + ve – type1 2-14 years, Anti-LKM + ve – type2 SLA- type3 Intermittent flare mimicking acute hepatitis

19. Drug-related liver injury Query for common drugs Liver biopsy to determine severity

20. Moderate/severe hepatocellular pattern of liver enzyme elevation History & Examination Fatigue, arthalgia , low-grade fever, jaundice > V iral Hepatitis Abdominal pain, Fever, jaundice > Acute biliary obstruction Presence of shock > Ischemic Hepatitis

21. Others Differential diagnosis - minor hepatitis viruses (EBV, CMV etc.), WD, hemochromatosis , and autoimmune , extrahepatic and congenital causes Up to 49% of patients with AIH present with moderate increase in aminotransferase levels and bilirbin Acute extrahepatic biliary obstruction - high AST levels (up to 10x ULN, with peak > 50x ULN in 1–2% of patients) USG/MRCP usually provide definitive diagnosis If Dx evaluation is negative for moderate t o severe aminotransferase elevation, a liver biopsy can be considered

22. Cholestasis Elevated ALP Could be physiological Liver and bone diseases are pathological cause Elevated GGT with raised ALP points to hepatocellular injury Drug-induced injury shows cholestatic pattern with normal USG ALP repeat after discontinuation of drugs at 6-8wks Disease specific markers are – ve , but ALP raised, then MRCP, liver biopsy should perform

23. PBC - no extrahepatic biliary obstruction with at least 2 of the following criteria ALP of at least 1.5x ULN AMA at a titer of 1:40 or higher H istological evidence of disease PSC is a chronic progressive disease with radiographic findings of abnormal bile ducts with wall thickening, dilation and stricture

24. Isolated Hyperbilirubinemia Unconjgated Hemolysis – markers of hemolysis Gilbert’s syndrome Drugs – rifampicin Crigler-najjer syndrome Conjugated Dubin-johnson syndrome Rotor syndrome

25. Conclusions Elevation of liver enzymes is one of the most common problems in the primary care setting History-taking and physical examination is very important for diagnosis Laboratory testing can be based on the pattern and degree of the elevation A systematic approach is help the clinician to find the cause of elevation

26. Thank You