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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