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MYSTERIOUS CASE OF JAUNDICEGuide – Prof Ravi K, Dr Kiran S
Dr Narayanaswamy, Dr Sudeep.
Presenter – Dr Devamsh G N.
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August 2016 November 2018 February 2019
A 58 YEAR OLD LADY, BANK MANAGER BY OCCUPATION...
FIRST VISIT REVISIT REVISITS AGAIN
WHY DID THE PATIENT VISIT US THRICE OVER THREE YEARS?
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FIRST VISIT AUGUST 2016
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A 58 YEAR OLD LADY…
Fever
Fever
• Lasted 5 days
• Low grade
• Intermittent
• No diurnal variations
History of• Generalized body ache
• Tiredness
No history of
• Cold, cough, pleuritic chest pain
• Nausea, vomiting
• Pain abdomen, abdominal distension
Yellowish discoloration
of eyes
• After fever subsided
• Progressive
No history of
• Herbal medication abuse
• Outstation travel
• Alcohol consumption
• Tattooing
• Weight loss, loss of appetite
• Bleeding manifestation
• Intravenous treatment/transfusion of blood products
Yellowish discoloration of the eyes
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HISTORY AND EXAMINATION
PAST HISTORY
• Hypothyroidism since 1 year on thyroxine suppliments
• No history of yellowish discoloration of eyes in the past
• No history of blood transfusions
• No history of hospitalizations / surgeries
PERSONAL HISTORY
• No history of alcohol consumption, drug abuse. Menarche attained. No peripartum complications.
FAMILY HISTORY
• No history of jaundice, liver disease in family members.
Hemodynamicallystable
BMI – 22.3 kg/m2
Icterus present
No other positive general physical
examination findings
Systemic examination was clinically within normal limits
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DIFFERENTIAL DIAGNOSIS
Acute viral hepatitis
Other infectious causes of hepatitis
Acute cholecystitis
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INVESTIGATIONS DONE IN FIRST VISIT
CBC
• Hb 14.2
• TC 5700
• Platelet count 1.6L
• MCV 92
LFT
• Total bilirubin 5.10 / Indirect bilirubin 1.2• Total protein 7.1/ Albumin 3.4/ Globulin 3.7
• AST 709
• ALT 1286• ALP 187
• GGT 178
RBS - 120mg/dL
Fasting lipid profile – Within normal limits
RFT – Within normal limits
TSH – 0.11
Acute viral hepatitis
• Viral markers
• HbsAg and IgM HbcAg – Non reactive
• Anti HCV antibodies– Negative
• IgM HAV and HEV – Negative
Other infectious hepatitis causes
• Peripheral smear for hemoparasites – Negative
• QBC - negative
• Leptospira IgM - Negative
Acute cholecystitis
• Ultrasound whole abdomen
• Liver normal size and echotexture. No EHBO.
• Gall bladder and CBD normal.
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TREATMENT
26/8/16 10/9/16 3/10/16 28/1/17
TOTAL BILIRUBIN 5.1 3.9 1.3 0.8
INDIRECT BILIRUBIN 1.2 0.7 0.5 0.7
TOTAL PROTEIN 7.1 7.4 8 6.9
ALBUMIN 3.4 3.4 3.5 3.7
GLOBULIN 3.7 4 4.5 3.2
AST 709 795 116 19
ALT 1286 1047 287 30
ALP 187 145 116 109
GGT 178 166 134 30
Supportive care given
Serial LFTs monitored
Patient improved and
was asymptomatic for 2 years.
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SECOND VISIT NOVEMBER 2018
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SECOND VISIT – NOVEMBER 2018
Patient presented with complaints of jaundice and tiredness since 5-6 days. No other complaints.
On examination, icterus present. No KF ring. Systemic examination clinically within normal limits.
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HEPATIC CAUSES FOR RECURRENT JAUNDICE
Alcoholic hepatitisExacerbations of
hepatitis BExacerbations of
hepatitis CCCF with
decompensation
Drug induced liver injury
Malaria
Preeclampsia/eclampsia/hyperemesis gravidarum/intrahepatic cholestasis
of pregnancy
Primary sclerosingcholangitis
Autoimmune hepatitis
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INVESTIGATIONS AT SECOND VISIT
CBC
• Hb 14.2
• Total count 5300
• Platelet count 1.6 lakhs
• PERIPHERAL SMEAR
• NORMAL STUDY
VIRAL MARKERS
• HbsAg and IgM HbcAg – Non reactive
• Anti HCV antibodies– Negative
• IgM HAV and HEV – Negative
ANA PROFILE
• NEGATIVE
PANEL FOR AUTOIMMUNE HEPATITIS
• ANTI SMOOTHMUSCLE ANTIBODY – NEGATIVE
• ANTI MITOCHONDRIAL ANTIBODY - NEGATIVE
• ANTI LKM AUTO ANTIBODY –NEGATIVE
PT/INR was within normal limits and UGIscopy showed normal
mucosal study
USG ABDOMEN
• Liver appears normal in size, coarse and lobulated. No focal parenchymal lesions, No biliary tree dilatation. Portal vein patent,13mm with periportaledema
• IMPRESSION- Diffuse liver disease
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SERIAL LFT REPORTS3/12/18 23/12/18 19/1/19
TOTAL
BILIRUBIN
6.3 5.8 3.4
INDIRECT
BILIRUBIN
1.8 1.9 1.3
TOTAL
PROTEIN
7.4 7.6 7.4
ALBUMIN 3.5 3.3 3.3
GLOBULIN 3.9 4.3 4.1
AST 1137 988 938
ALT 723 564 556
ALP 259 207 209
GGT 145 100 131
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Supportive care given
Serial LFTs monitored
THIRD VISIT - FEBRUARY 2019
20/2/19
TOTAL BILIRUBIN 6.6
INDIRECT BILIRUBIN 1.6
TOTAL PROTEIN 7.4
ALBUMIN 2.0
GLOBULIN 5.4
AST 665
ALT 292
ALP 250
GGT 120
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Patient presented with persistent jaundice. No other complaints.
On examination, icterus present. Systemic examination clinically within normal limits.
MRCP DONE IN MARCH 2019
No evidence of primary biliary cirrhosis/primary sclerosing cholangitis.
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OTHER INVESTIGATIONSEXTENDED AUTOANTIBODY PANEL FOR HEPATITIS
• ANTI MITOCHONDIRIAL ANTIBODY –NEGATIVE
• ANTI LKM-1/3 – NEGATIVE
• ANTI SLA/LP – NEGATIVE
• ANTI LC-1 - NEGATIVE
SERUM PROTEIN ELECTROPHORESIS
• TOTAL PROTEIN – 6.57
• ALBUMIN – 3.41
• GLOBULIN – 3.16
• GAMMA GLOBULIN – 1.73
• IMPRESSION – CHRONIC INFLAMMATORY PROCESS
Wilsons and hemochromatosis workup-Negative
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HEPATIC CAUSES FOR RECURRENT JAUNDICE
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Alcoholic
hepatitis
Exacerbations
of hepatitis B
and hepatitis C
CCF with
decompensation
Drug induced
liver injuryMalaria
Recurrent
jaundice in
pregnancy
Primary sclerosing
cholangitis
Autoimmune
hepatitis
TIMELINE - A 58 YEAR OLD LADY, BANK MANAGER BY OCCUPATION...
FIRST VISIT REVISIT REVISITS AGAIN
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AUGUST 2016
• Fever
• Yellowish discoloration of eyes and urine
• Acute viral hepatitis -Supportive care give.
NOVEMBER 2018
• Tiredness
• Yellowish discoloration of eyes
• Recurrent hepatitis –Investigated and treated symptomatically
FEBRUARY 2019
• Yellowish discoloration of eyes
• Further evaluation and liver biopsy
LIVER BIOPSY – MARCH 2019
MICROSCOPIC EXAMINATION The liver shows micro and macro nodules surrounded by
fibrous stroma. The hepatocytes show ballooning degeneration with groups and individual cell hepatocytolysis with neutrophilic infiltration. Majority of lobules show bridging necrosis with interface hepatitis. Few hepatocytes show reparative atypia. No fatty degeneration seen. The portal tracts are markedly widened and show bile duct proliferation. Dense portal fibrosis seen and the portal tracts are infiltrated with lymphocytes, occasional eosinophils and lymphoid follicle formation. Portal to portal and portal to central fibrosis seen. There is total distortion of hepatic vascular network. Mild cholestasis seen. No evidence of malignancy.
Chronic active hepatitis with cirrhosis.
HAI grading 12/18
HAI staging 6/6
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DIAGNOSTIC ALGORITHM
WHAT CAME TO OUR RESCUE?!
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OUR PATIENT’S SCORE - 17
FINAL DIAGNOSIS
AUTOANTIBODY NEGATIVE AUTOIMMUNE HEPATITIS.
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OUR PATIENT
Started on steroids.
Started on Azathioprine
• Tremors
• Dose adjusted
Currently on low dose steroids and
azathioprine
Serial LFTs monitored
3/12/18 15/5/19
TOTAL
BILIRUBIN
6.3 1.2
INDIRECT
BILIRUBIN
1.8 0.6
TOTAL
PROTEIN
7.4 6.6
ALBUMIN 3.5 2.9
GLOBULIN 3.9 3.7
AST 1137 56
ALT 723 53
ALP 259 107
GGT 145 117
BEFORE AFTER
STEROIDS AND AZATHIOPRINE
PATIENT IS CURRENTLY
ASYMPTOMATIC
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AUTOANTIBODY NEGATIVE AUTOIMMUNE HEPATITIS
1. Worldwide prevalence of autoimmune hepatitis is around 1-12 cases per 1 million. Approximately 10-20% are sero-negative.
2. 13 percent of all adults with chronic hepatitis of undetermined cause satisfy international criteria for diagnosis of autoimmune hepatitis but lack auto antibodies.
3. Autoantibody negative autoimmune hepatitis patients are labelled as having CRYPTOGENIC chronic hepatitis.
4. They are denied therapies of potential benefit and end up developing cirrhosis and its complications. Median survival is 12.2 years in patients treated as compared to 3.3 years in untreated patients.
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TREATMENT – WHEN TO TREAT?
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HOW TO TREAT?
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TAKE HOME MESSAGE
Auto antibody negative autoimmune hepatitis must be considered before labelling a patient as having cryptogenic hepatitis/cirrhosis.
Clinicians should be aware of the scoring systems for autoimmune hepatitis. Do not rely solely on auto antibodies to diagnose autoimmune hepatitis.
Autoimmune hepatitis patients treated with azathioprine can develop tremors as a dose dependent side effect.
Identifying and treating autoimmune hepatitis significantly reduces morbidity and mortality.
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THANK YOU
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REFERENCES
1. Kasper, D. and Harrison, T. (2005). Harrison's principles of internal medicine. New York: McGraw-Hill, Medical Pub. Division.
2. Sherlock S, Dooley J. Diseases of the liver and biliary system. 11th ed. Oxford: Blackwell Science; 2002.
3. LEISENGER, M. H., FELDMAN, M., FRIEDMAN, L. S., & BRANDT, L. J. (2010). Sleisenger and Fordtran's gastrointestinal and liver disease: pathophysiology, diagnosis, management. Philadelphia, Saunders/Elsevier.
4. Fatih Karaahmet, Hakan Akinci, Rasit Ayte, Mevlut Hamamci, Yusuf Coskun, IlhamiYuksel, Tremor as dose dependent side-effect of azathioprine in remission patient with ileal Crohn's disease, Journal of Crohn's and Colitis, Volume 7, Issue 9, October 2013, Page e404.
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