Practical approach to fever with altered liver functions

approach to fever with altered liver function tests

1. Practical approach to Fever with altered Liver function tests

2. Introduction A thorough history, physical examination, and standard laboratory testing remain the basis of the initial evaluation of the patient with Fever with altered liver parameters Newer diagnostic modalities, including updated serology, viral cultures, computed tomography, and magnetic resonance imaging, ERCP, have important roles in the assessment of these patients.

3. Differential Dignosis Malarial Hepatitis Typhoid hepatitis Leptospirosis Viral Hepatitis Infectious Mononucleosis Herpes simplex virus Tuberculosis Connective tissue disorders: ASOD Auto immune diseases Liver abscess Acute Cholecystitis Cholangitis Drug fever

4. Malarial Hepatitis Anand criteria: demonstration of P. falciparum infection. at least 3 fold >ALT, demonstrated on two consecutive blood samples taken over24 h apart with or without conjugated hyperbilirubinemia. absence of clinical and serological evidence to suggest drug or viral hepatitis. clinical response to antimalarial drugs or autopsy evidence of disseminated falciparum infection.

5. Malarial Hepatopathy: Heterogenous Syndrome Comparison of clinical features of two types of malarial hepatitis. Horizontal axis shows time in days, while vertical axis shows severity of clinical abnormality. Malarial hepatitis can be classified into two clinical types. Type B : relatively benign condition Type A : associated with multiorgan failure

6. Malaria vs Fulminant Hepatic failure Malaria History of fever, Headache, Altered sensorium, urinary output, vomiting, convulsions, coma Hepato-splenomegaly Anemia unconjugated hyperbilirubinemia Mild elevation of enzymes complications Renal failure/ARDS/ Septicemia Acute Viral Hepatitis (FHF) Fever in prodrome with anorexia,nausea , vomiting Jaundice Conjugated Hyperbilirubenemia Marked elevation of enzymes AST/ALT >1000 IU Viral markers Hepatitis A ,B,C,D,E

7. Typhoid hepatitis The criteria (clinical and laboratory tests) used for this study included Persistence of fever with jaundice Hepatomegaly abnormal liver biochemistry conjugated hyper bilirubinaemia moderately elevated serum transaminases a negative serology for viral hepatitis . AST:LDH < 4 A positive blood culture for Salmonella typhi to differentiate Salmonella Hepatitis from other causes of Acute Hepatitis

8. Leptospirosis Weils disease Viral Hepatitis onset sudden gradual headache constant occasional Muscle pain severe Mild Conjuctival injection Present Absent disorientation common Rare Haemorrhagic diathesis common Rare Nausea and vomiting present Present Abdominal discomfort common Common bronchitis present Absent albuminuria present Absent Leucocyte count Polymorphs leucocytosis Leucopenia lymphocytosis

9. Acute viral hepatitis Symptoms related to acute viral hepatitis are variable and nonspecific. It is impossible to distinguish one form of viral hepatitis from the other based solely on clinical features. The clinical course of hepatitis varies widely from an asymptomatic phase recognized only by elevation in aminotransferase levels to fulminant hepatitis with frank jaundice and hepatic coma

10. Clinical overview of five viral hepatitis VIRUS Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus Source stool blood blood blood stool Transmission enteric Percutaneous/per mucosal Percutaneous/per mucosal Percutaneous/per mucosal enteric Epidemic yes no no no yes Acute Hepatitis yes yes yes yes yes Fulminant Hepatitis yes yes yes yes yes Chronicity no yes yes yes no HCC no yes yes yes no

11. Hepatitis A virus IgM anti HAV Hepatitis B virus HBsAg / IgM anti HBc Hepatitis C virus HCV RNA Hepatitis D virus HBsAg / HDV RNA Hepatitis E virus IgM anti HEV / HEV RNA EBV virus Monospot test / IgM anti EBV CMV IgM anti CMV Herpes simplex virus 2 HSV 1 ,2

12. Infectious Mononucleosis Fever Sore throat Rash Lymphadenopathy Jaundice Tender splenomegaly Hepatomegaly Leucocytosis Monospot test :Positive IgM EBV : Present

13. Herpes Simplex Hepatitis uncommon Frequently Fulminant type Signs and symptoms are non-specific fever, anorexia, n/v, abdominal pain, leukopenia, and coagulopathy Skin, mouth, and/or genital lesions Typical LFT pattern is marked rise in transaminase levels without elevated bilirubin (most patients do not have jaundice)

14. Tuberculosis of the liver Pyrexia of unknown origin. Jaundice may appear in overwhelming miliary TB Serum globulin is increased so that the A/G ratio is reduced. ALP is disproportionately elevated Rarely, multiple caseating granulomas lead to massive hepatosplenomegaly and death in liver failure Hepato-splenic tuberculosis. CT scan showing scattered filling defects in the liver and spleen

15. Adult onset Still’s disease (AOSD) rare systemic inflammatory disorder of unknown etiology. Hepatic involvement is frequently observed in the course of AOSD with mildly elevated transaminases and/or hepatomegaly. Fulminant hepatic failure, occasionally requiring urgent liver transplantation, is a rare manifestation of AOSD. Yamamuchi criteria Major Arthralgia > 2 weeks Fever >39 ,intermittent 1 week Typical rash Leucocytosis Minor LFT abnormal Sore throat Lymphadenopathy Negative ANA / RF 5 criteria (3 major)

16. Autoimmune hepatitis Autoimmune hepatitis may present as an acute hepatitis in up to 30% of cases The typical presentation is that of a young woman with a high titer of antinuclear antibody and smooth muscle antibody or anti-LKM (liver/kidney/ microsome antibody) and other clinical evidence of autoimmune disorders such as arthralgias and autoimmune hemolytic anemia. The globulin level may not be elevated during an acute presentation. Testing for the HLA markers A1, B8,and DR3 may provide substantiating evidence for confirming the diagnosis of autoimmune hepatitis.

17. Wilsons disease Wilson disease is “the great imitator” and has diverse presentations, including that of acute hepatitis The diagnosis is difficult to confirm during an acute presentation and requires a high index of suspicion. It is important to establish the diagnosis early because of an extremely high mortality rate. In a recent series of fulminant hepatitis, no patients with Wilson disease referred to a transplantation center survived despite undergoing OLT The usual diagnostic criteria may be normal during an acute presentation. Ceruloplasmin level may be normal because of widespread release from necrosed hepatocytes, and urinary copper excretion may be low owing to altered renal clearance. Diagnostic clues may be the young age of the patient, a low alkaline phosphatase level, and the presence of a hemolytic anemia.

18. Evaluation of the patient with elevated serum aminotransferase levels Hepatitis B virus serology Chronic hepatitis B infection HCV antibodies and HCV RNA Chronic hepatitis C infection ANA and SMA Autoimmune hepatitis Ferritin Hemochromatosis ceruloplasmin Wilsons disease AST/ALT >2 and alcohol history Alcoholic hepatitis SPEP Alpha 1 anti trypsin deficiency Hepatic ultrasonography Macrovesicular steatosis on liver Biopsy NASH Antiendomysial and tissue transglutaminase antibodies Small bowel biopsy Celiac disease

19. DD & Management of chronic hepatitis

20. Acute cholecystitis Clinical Presentation RUQ Pain (Radiating to shoulder (R) , N/V , Fever P/A Examination RUQ tenderness / Guarding / Rigidity + CHG:Hb gms %, Hct , WBC 13.2, 39%, 13000 Electrolytes Normal LFTs Bil : 1.8, AST :110, ALT :140 , ALP: 170 Amylase / lipase Normal Prothrombin Time /INR Normal ECG Normal USG Abdomen Gallstone, GB wall thickening ,Pericholecystic fluid collection, Murphy’s Sign Thickened gallbladder wall (> 4mm) Pericholecystic fluid or Subserosal oedema without ascites, intramural gas HIDA Scan Non filling of the gall bladder after 1 hour

21. USG ABDOMEN Calculous cholecystitis Acalculous cholecystitis

22. HIDA SCAN ACUTE CHOLECYSTITIS RIM SIGN Further delayed images were obtained at 3 h severe inflammation & increased likelihood of complications such as gangrene and perforation. The technetium 99m-labeled hepatic iminodiacetic acid ([99mTc]HIDA) study showed nonfilling of the gallbladder at 1 h

23. Liver abscess AMOBEIC LIVER ABSCESS PYOGENIC LIVER ABSCESS age Usually <50 years Usually >50 years Gender M> F M= F Diarrhoea More often than bacterial liver abscess but not obligatory Rare Concomitant disease Rare Frequent (bile duct diseases, diverticulitis, tumors ) Number Usually solitary Often multiple Serological test Positive in 95% of cases Negative Blood culture Negative Often Positive Contents Yellowish-brown to anchovy colored,odorless Yellowish, malodorous

24. Ultrasound Abdomen Ameobic liver abscess cystic hypoechoic appearance on ultrasound. ultrasound images showing multiple, hypoechoic , loculated fluid collections within the parenchyma of the liver, consistent with hepatic abscesses

25. Diagnostic workup of patients with suspected Bacterial cholangitis Signs and symptoms Fever, jaundice, RUQ pain, confusion, hypotension Biochemical test Leukocytes, CRP, bilirubin, alkaline phosphatase, lipase Microbiological tests Bood culture Imaging Abdominal USG , EUS, MRC Imaging and treatment ERCP

26. CHOLEDOCHOLITHIASIS USG ABDOMEN ERCP

27. DILI

28. Lab parameters in different DILI PARAMETERS HEPATOCELLULAR INJURY CHOLESTATIC INJURY MIXED LIVER INJURY ALT >2 ULN - >2 ULN ALP - >2 ULN >2 ULN ALT/ALP >5 <2 2-5

29. Investigating drug induced liver disease Suspect any drug Contact manufacturer and Safety of Medicines Organization Drug history All medicines, dose, duration, previous administration De-challenge Rapid fall in transaminases Re-challenge Inadvertent Deliberate usually impossible Exclude other liver Hepatitis A, B and C; autoimmune; biliary diseases obstruction Liver biopsy If necessary fat, granulomas, zonal hepatitis, bile duct lesions

30. Thank you