Hepatitis, acute liver failure

Krisztina Hagymási

2016

25-y female patient

Past history (anamnesis)

- Kawasaki disease (1 y old)

- 2012 : M. Crohn: azathioprine, mesalasine, methylprednisolone

-since 2014: biological treatment

-Last colonoscopy: 2014.10.: ulcers in the coecum, fl. hepatica, fl.

lienalis, sigma

- (family history: mother: psoriasis, grandfather: ulcerative colitis,

brother: asthma bronchiale)

2016.01.15 admission at 2nd Dept Int Med

- 5-day fever, weakness, knee pain, methimazole administration (daily

1000-1500 mg)

- Before the day of admission: 500 mg ciprofloxacin, 500 mg

acetaminophen

- Symptoms: epigastric pain, no diarrhea

- Medications: Humira, Salofalk, Medrol, Imuran, Aktiferrin, Kaldyum

Examinations:

- Labs:

- - INR: 1,35; - Alb.: 36,9; - GOT: 8212; - GPT: 3642; - GGT: 164; T. bil.: 13,5; -

We: 6; - CRP: 220; - Pct: 0,8; - WBC: 0,85, - Htk: 0,36; - Tc.: 65; ANC: 460/ul -

Na: 129; - K: 4,1; - Urine: protein:++ , bact.: +++

- Imagings: - Chest X ray: negative

- Abdominal US: negative

- For infectious etiology:

- Ear-nose-throat examination: mild tonsillopharyngitis (no explanation fever)

- Hemoculture was taken

- Hepatitis erology were not available (Friday nightshift)

- Infectological consultation: Tienam

- For hematological etiology:

- Sternal puncture: good granulopoesis, normoblastic erythropoesis, no abnormal blast count, many megakaryocytes, dg.: septicaemia + hepato- and bone marrow toxic drug effects

Isolation, suspected druges were stopped, antibiotics with broad spectra

- Labs:

- 15.01.2016. (21:00):

- - INR: 1,81; - Alb.: 24,4; - GOT: 9456; - GPT: 4637; - GGT: 179; T. bil.: 17,2;

LDH: 6248; - CRP: 155,8; - WBC: 0,96, - Htk: 0,30; - Tc.: 51; - Na: 129; - K: 4,1;

- 16.01.2016.:

- : - INR: 2,37; - Alb.: 23; - GOT: 13709; - GPT: 6010; - GGT: 215; -

ALP: 110; - LDH: 8251; - T. bil.: 21,5; - Ammonia: 65; ChE: 4707; -

CRP: 156,6; - Pct: 2,19; - WBC: 1,62; - Htk: 0,27; - Tc.: 44; - Na:

127; - K: 4,0

• Progressive hepatic failure - Transmission to the Transplantation Clinic

- Tx list

- Brain, chest, abdominal CT: no edema cerebri, bilateral pulmonary infilttratum, hepatomegaly, diffuse liver lesion, portal hypertension

- Respiratoty failure, ARDS, hemodyalisis, GIV

- Serology:

CMV IgG: poz.; CMV IgM: kétes; CMV Ag.: neg.; EBV IgM: neg.; HBsAg: neg., anti-HCV: neg., anti-HAV IgM: neg., Clostridium Ag and toxin neg.

- Oral mucosa: HSV-1 PCR pozitív!

Lab controls every 6 hours

Lab results

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GOT GPT LDH Kolinészteráz

INR

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• 2016.01.19.: liver transplantation

• Histology: fulminant necrosis with severe steatosis, etiology is

not clear, a1at-deficiency, hemochromatosis, Wilson’s disease

can be excluded, toxic etiology is suspected

28-y female patient

• No past significant history

• 27-w pregnancy

• Itching

• Labs:

• Tbi: normal, dibi: 6, GOT: 96 GPT: 116 ALP: GGT

• Ultrasound: negative

• Anti-HBS >20

• HBsAG: negative

• Anti-HCV: positive

Etiological factors • Nonalcoholic fatty liver disease (NAFLD/NASH) (diagnosis of

exclusion)

• Alcohol consumption, drug induced liver disease (DILI) (Anamnesis, diagnosis of exclusion)

• Viral infections-not just primary hepatotropic viruses (HBsAG, a-HCV…)

• Autoimmune Diseases:

– Autoimmune Hepatitis: (ANA, SMA, LKM1, SLA)

– PBC (AMA)

– PSC (ANCA)

• Storage Diseases:

– Iron-hemochromatosis (Fe, TVK, Ferritin)

– Copper-Wilson disease (Cu, Ceruloplasmin)

- a1-Antitripsin deficiency (A1T)

Acute Damage to the Liver

. Hepatocellular

ALT↑↑

Combined: ALT↑ ALP↑

Cholestatic

ALP ↑↑

GGT ↑↑

ALT ↑

Pathognomonics: 1. anti-HAV IgM

2. HBsAg

3. anti-HBc IgM

4. anti-HCV

5. ANA, SMA

6. EBV, CMV

7. Ceruloplasmin

8. Alcohol?

9. Drugs?

Pathognomonics: 1. AMA

2. Drugs?

3. US/MR

4. ERCP/MRCP

Liver Biopsy: Only in those patients in whom diagnosis

can NOT be done by any other means.

Chronic Liver Damage:

. Hepatocellular:

ALT↑↑

Combined: ALT↑ ALP↑

Cholestatic:

ALP ↑↑

GGT ↑↑

ALT ↑

Pathognomonics: 1. HBsAg

2. anti-HCV

3. Fe,Ferritin

4. Ceruloplasmin

5. a1-antitripsin

6. ANA, SMA

7. US

8. Alcohol?

Pathognomonics: 1. Drugs?

2. AMA

3. p-ANCA

4. US

5. ERCP/MRCP

Liver biopsy: sometimes it has a pathognomonic value

Prognostic: necroinflammation (grading), fibrosis (staging)

Primary hepatotrop viruses

Secondary hepatotrop viruses

• Herpesviruses

– EBV, CMV, Herpes simplex, Varicella zooster

• Togaviruses

– Rubeola

• Picornaviruses

– Coxsackie, ECHO

• Paramyxoviruses

– Mumps, morbilli

• Adenoviruses

• HIV

• Exotic viruses

– Marburg, Ebola, Arena, Lassa, Hanta, dengue-fever

Clinical syndromes

• Acute hepatitis

– nausea, appetite loss, right subcostal pain, subfebrility,

fatigue, weakness

– acute fulminant hepatitis (rare, encephalopathy, icterus,

ascites, PI prolongation)

• Chronic hepatitis

– asymptomatic, fatigue, weakness

• Cirrhosis

• Liver failure

• Hepatocellular carcinoma

HCV treatment

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1991 1998 2003 2011 2020

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2-7%

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PEG-

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59-75%

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100% ?

HCV cell cycle- future drugs