Liver failure + Hepatitis

Question 1

What is liver failure?

Answer 1

Refers to the loss of liver function and the development of complications including coagulopathy, jaundice or encephalopathy.

Can occur:
acutely (onset of symptoms <26weeks with a previous healthy liver)
- can be divided into hyperacute (<7days), acute (8-21days), or subacute (4-26weeks).

chronically
- pt has a background of liver cirrhosis

Question 2

Causes of acute liver failure?

Answer 2

Viral hepatitis (Hep A, B and E infections)

Drug-induced liver injury (overdose or adverse reactions to meds like paracetamol, halothane, isoniazid, certain abx)

Toxic exposures (e.g. industrial chemicals, Amanita phalloides mushrooms)

Vascular disorders (e.g. Budd-Chiari syndrome)

Vascular disorders

Question 3

Causes of chronic liver failure?

Answer 3

Alcohol misuse (chronic alcohol consumption → cirrhosis and liver failure)

Chronic Viral Hepatitis (persistent Hep B or C virus)

NAFLD (Non-Alcoholic Fatty Liver Disease; accumulation of fat in the liver; associated with obesity and metabolic syndrome)

Autoimmune liver (e.g. autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis)

Hereditary Conditions (e.g. haemochromatosis, Wilson’s disease, and alpha-1 antitrypsin deficiency)

Question 4

Presentation of acute liver failure?

Answer 4

Right upper quadrant pain
N+V
Malaise
Sweet smelling/musty breath (fetor)
Disorientation, slurring of speech, confusion, agitation, sleepiness, flapping tremor, personality change, coma (features of encephalopathy)

Manifestations of failure of the liver to perform its functions:
* Abnormal blood clotting
* Jaundice - uncommon unless subacute liver failure
* Low glucose
* High blood lactate
* Impaired renal function
* Acidosis
* Hyperammonaemia
* Infection

Question 5

Risk factors of acute liver failure?

Answer 5

Hepatotoxic drugs
Contaminated food/water (Hep A and E)

Blood borne virus risks (Hep B)
- unprotected sex
- tattoos/piercings with unclean equipment
- recreational drug use -shared paraphernalia

Recreational drugs -mushrooms, ecstasy

Underlying liver disease

Question 6

Investigations for liver failure?

Answer 6

INR (coagulopathy and establish diagnosis of liver failure)

LFTs (including albumin, bilirubin)

FBC (leucocytosis -infection; thrombocytopaenia -chronic liver disease; anaemia)

U&Es (includes sodium, potassium, urea, creatinine, eGFR)

Tests to determine cause:
- Paracetamol level (paracetamol overdose)
- Hepatitis
- Epstein-Barr virus
- Cytomegalovirus serology (viral infection)
- Iron studies (haemochromatosis)
α-1 anti-trypsin (α-1 antitrypsin deficiency)
- Caeruloplasmin level (Wilson’s disease)
- Iron studies (hereditary haemochromatosis)
- Auto-antibodies (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis)

Imaging:
- ascites present →peritoneal tap for microscopy and culture for spontaneous bacterial peritonitis.
- abdominal US
- Doppler US →Budd-Chiari syndrome
- OGD →variceal bleeding

Question 7

Management of liver failure?

Answer 7

Resuscitate
- protect airway
- correct volume depletion, hypoglycaemia
- avoid hyponatraemia

For encephalopathy:
- grade stage of encephalopathy
- offer lactulose (help nitrogenous waste loss through the bowels; reduces encephalopathy)
- offer rifaximin (2nd line abx; reduces nitrogen forming microorganism in gut)
- offer IV mannitol (reduce cerebral oedema)

For paracetamol overdose:
- offer IV N-Acetyl Cysteine

For coagulopathy:
- IV vitamin K (helps produce coagulation factors)
- Fresh frozen plasma can be given if patient is bleeding

For spontaneous bacterial peritonitis:
- IV Piperacillin-Tazobactam (1st line broad spectrum abx)

Haemofiltration

Liver transplant if predicted poor outcome in acute liver failure.

Liver transplant (paracetamol induced):
Arterial pH <7.3 24h after ingestion OR
- Pro-thrombin time >100s
- AND creatinine >300µmol/L
- AND grade III or IV encephalopathy.

Liver transplant (non-paracetamol induced):
Prothrombin time >100s OR
Any three of:
- Drug-induced liver failure
- Age <10 or >40 years
- 1 week from 1st jaundice to encephalopathy
- Prothrombin time >50s
- Bilirubin ≥300µmol/L.

Question 8

How is encephalopathy graded?

Answer 8

Grade 1
Altered mood and behaviour, disturbance of sleep pattern, dyspraxia

Grade 2
Drowsiness, confusion, slurring of speech, personality change

Grade 3
Incoherency, restlessness, asterixis

Grade 4
Coma

Question 9

Complications of liver failure?

Answer 9

Bacterial infection
Fungal infection
Cerebral oedema +/-raised intracranial pressure
Bleeding
Hypoglycaemia
Multi-organ failure

Question 10

What is hepatitis?

Answer 10

Refers to inflammation of the liver caused by a variety of infectious and non-infectious factors.

Question 11

Causes of hepatitis?

Answer 11

Hepatitis A, B, C, D, E (5 types of viral hepatitis)
Drugs
Toxins
Alcohol
EBV
CMV
Malaria
Leptospirosis

Question 12

What are the most prevalent causes of viral hepatitis in the UK?

Answer 12

Hepatitis A, B, and C viruses.

Question 13

Which hepatitis viruses can lead to acute liver failure?

Answer 13

Hepatitis A and Hepatitis E

Question 14

Which hepatitis viruses can lead to chronic liver failure?

Answer 14

Hepatitis B and Hepatitis C

Question 15

Which patients experience hepatitis D?

Answer 15

Hepatitis D only occurs in pts infected with hepatitis B.

Question 16

Presentation of acute liver failure?

Answer 16

Predominantly caused by Hepatitis A and E

Prodromal viral illness:
- Fever
- Malaise
- Anorexia
- Nausea and vomiting

Question 17

Presentation of acute hepatitis?

Answer 17

Right upper quadrant pain
Jaundice
Tender hepatosplenomegaly (due to swelling of the liver capsule)

Question 18

Presentation of chronic liver failure?

Answer 18

Hepatic encephalopathy
Jaundice
Ascites
Coagulopathy due to abnormal clotting

Question 19

How is Hepatitis A transmitted? Is there a vaccine to prevent Hep A?

Answer 19

RNA virus transmitted via the faecal-oral route (occasionally through food sources or through anal sex).

Vaccine available.

Question 20

Presentation of Hep A?

Answer 20

Flu-like symptoms followed by:
- jaundice
- pale stools (in some)
- dark urine
- abdominal pain

Incubation period of 2-6 weeks

Presents ONLY as an acute hepatitis with no chronic phase

Complete recovery can take up to 6 months.

Question 21

Investigations of Hep A?

Answer 21

LFTs with ALT/AST as high as in the 1000s.
Ig M and IgG antibodies.

Question 22

Management of Hep A?

Answer 22

Supportive management

Question 23

How is Hepatitis E transmitted? Is there a vaccine to prevent Hep E? Is it dangerous in pregnancy?

Answer 23

RNA virus transmitted via the faecal-oral route, commonly undercooked pork.

Extremely dangerous in pregnancy, with mortality rate up to 20%.

Vaccine NOT available.

Question 24

What is hepatitis B?

Answer 24

dsDNA virus of Hepadnaviridae family.

Causes acute hepatitis and can progress to chronic hepatitis infection.

Globally common

Incubation period usually 60-90 days.

Question 25

How is Hepatitis B transmitted? Is there a vaccine to prevent Hep B?

Answer 25

dsDNA virus of Hepadnaviridae family transmitted via infected blood or body fluids.

E.g. vaginal/anal intercourse, transfusion, vertical transmission -pregnancy.

Vaccine available.

Question 26

Presentation of Hep B?

Answer 26

Children:
- mostly asymptomatic
- jaundice

Adults:
- jaundice
- fever
- malaise
- viral prodrome
- darkening of urine
- lightening of stool
- ascites
- encephalopathy

Rare features:
- glomerulonephritis
- cryoglobulinaemia
- polyarteritis nodosa

If pt is worsening, consider co-infection with Hep D.

Question 27

Investigations for Hep B?

Answer 27

HBsAg (surface antigen) –active infection; persists >6months

HBeAg (E antigen) –active viral replication; implies high infectivity

HBcAb (core antibodies) –IgM = acute infection; IgG = implies past infection or vaccination

HBV DNA (Hepatitis B virus DNA) –quantifies viral overload; monitor response to tx

Anti-HBs (Hepatitis B Surface Antibody) -indicates immunity from past infection or vaccination.

Anti-HBe (Hepatitis B e Antibody) -indicates lower infectivity; seroconversion is associated with reduced viral infection.

Biopsy
- for chronic Hep B infection
- ‘ground glass’ hepatocytes on light microscopy

Question 28

Management of Hep B?

Answer 28

Antiviral tx:
- 1st line: pegylated interferon
- 2nd line: pegylated interferon alfa-2a

Offering symptomatic supportive treatment (rest, pain relief, and treatment of nausea and itch

Avoid alcohol

Question 29

What is Hep C infection? How is it transmitted? Is there a vaccine for prevention?

Answer 29

RNA virus of the Flaviviridae family.

Transmitted via exchange of blood and bodily fluids.
E.g. IV drug use, blood transfusion, haemodialysis, sexual transmission, needlestick injuries, perinatal infection from infected mother.

Incubation period of 6-9 weeks.

Vaccine NOT available.

Question 30

Presentation of Hep C?

Answer 30

Mostly asymptomatic
Can develop into chronic infection

Fever
Fatigue
Abdominal pain
N+V
Jaundice

Arthralgia (pain in the joints)
Sjogren’s syndrome
Cryoglobulinaemia
Porphyria cutanea tarda
Membranoproliferative glomerulonephritis

Question 31

Investigations for Hep C?

Answer 31

Anti-HCV serology (may take months to become +ve; can remain positive even if the virus has been cleared)

HCV RNA (if +ve for more than two months, treat it)

FBC (check for anaemia, neutropenia, and thrombocytopenia)
U&Es (CKD can lead to extrahepatic manifestation)
LFTS (ALT, GGT)
HbA1c
TFTs (antiviral therapy can lead to thyroid dysfunction)
Ferritin (raised in Hep C)
HBsAg
HAV-IgM
HIV
STI screening

Question 32

Management of Hep C?

Answer 32

Direct-acting antiviral (e.g. Sofosbuvir)

Sofosbuvir and daclatsavir may be used as combination therapy

Manage underlying cirrhosis.