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 Percutaneo
us/per
mucosal
Percutaneo
us/per
mucosal
Percutane
ous/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