Viral hepatitides (I) Flashcards
What type of viruses cause hepatitis A&E?
RNA viruses that follow an acute course
What virus causes hepatitis A?
RNA picornavirus
What virus causes hepatitis E?
Calcivirus
What is the route of transmission and incubation period for hepatitis A&E?
Faecal oral route, 3-6 weeks incubation period
When is hepatitis A&E considered non-infectious?
Patients considered non-infectious 1 week after onset of jaundice
What is a common cause of hepatitis A?
Shellfish
What is hepatitis E most commonly spread by?
Undercooked pork
Where is hepatitis A endemic?
- developing world - infection often occurs sub-clinically
- better sanitisation in developed world = less common
Where is hepatitis E endemic?
Asia, Africa, Central America
Which group is hepatitis A associated with?
Travellers
Which type of hepatitis is more common in pregnant women?
Severe hepatitis in pregnant women - hepatitis E
What types of antibodies are involved in hepatitis A&E?
IgM produced, then IgG, then immunity
Who is chronic hepatitis E limited to?
Almost exclusively limited to immunosuppressed patients
(Chronic HEV = >3mth)
What kind of virus is hepatitis B?
Double-stranded DNA hepadnavirus
Enveloped, partially double-stranded DNA virus
What viral proteins does hepatitis B contain? (3)
- core antigen (HBcAg)
- surface antigen (HBsAg)
- e antigen (HBeAg) - marker of high infectivity
What kind of virus is hepatitis D?
- single-stranded RNA virus coated with HBsAg
- defective virus - requires hepatitis B surface antigen to complete its replication and transmission cycle
- only co-infects those with HBV or superinfects those who are already carriers of HBV
Who can hepatitis D affect? (2)
- co-infect with hepatitis B
- superinfect those who are already carriers of hepatitis B - we suspect hepatitis D superinfection in chronic Hep B patients who have flare-ups
How is hepatitis B&D transmitted? (3)
- sexual contact
- blood
- vertical transmission (mother to child)
What is the incubation period for hepatitis B&D?
3-6 months
What are there no antibodies to in hepatitis B&D vaccination?
HBcAg (core antigen)
What do carriers of hepatitis B/D never make antibodies to?
HBsAg (surface antigen)
Where is hepatitis B/D common?
Southeast Asia, Africa and Mediterranean countries
What kind of virus is hepatitis C?
Small, enveloped, single-stranded RNA virus
What is classed as acute vs chronic hepatitis C?
- acute <6 months
- chronic >6 months - most common type of hepatitis to become chronic
How is hepatitis C transmitted? (3)
- sexual contact
- blood
- vertical transmission (mother to child)
What is the incubation period for hepatitis C?
2 weeks to 6 months
Is there a vaccine for hepatitis C?
No
What is the most common liver infection globally?
Hepatitis B
Why do we generally get jaundice and pruritus in viral hepatitis?
Liver inflammation and hepatocyte necrosis caused by immune response = bilirubin with bile salts released into bloodstream –> jaundice + pruritus
Why do we generally get dark urine and pale stool in viral hepatitis?
Bilirubin from blood is filtered by kidneys and ends up in urine instead of stool
What does histology show in viral hepatitis?
- inflammatory cell infiltration of portal tracts (neutrophils, macrophages, eosinophils, lymphocytes)
- zone 3 necrosis
- bile duct proliferation
How often is hepatitis E asymptomatic?
Approximately 95% of patients with acute hepatitis E infection are asymptomatic
When is hepatitis A/E more likely to be asymptomatic?
Children
What are the clinical features of hepatitis A&E? (6 + 4)
- acute
- prodromal period - malaise, anorexia, fever, N&V, headache (before jaundice)
- hepatitis:
- dark urine
- pale stools
- jaundice
- pruritus/itching
- RUQ pain
- pyrexia
- hepatomegaly
How many recover from hepatitis A/E?
85% make full recovery within 3 months
What are the clinical features of hepatitis B/D? (8)
- asymptomatic
- incubation period 3-6 months
- prodromal features - malaise, headache, anorexia, N&V, diarrhoea, RUQ pain
- jaundice
- dark urine - increased conjugated BR in urine
- hepatomegaly
- ascites
- maculopapular or urticarial rash (part of serum sickness-like syndrome)
What might you see on examination of hepatitis B/D? (2)
- cervical lymphadenopathy
- chronic liver disease/cirrhosis symptoms
How does hepatitis C usually present?
90% of acute infections are asymptomatic
What are the clinical features of hepatitis C? (6)
- asymptomatic
- constitutional Sx - fatigue, myalgia, arthralgia
- jaundice
- ascites
- signs of hepatic encephalopathy (confusion, altered consciousness, coma)
- extrahepatic manifestations
What other diseases can hepatitis C lead to? (7)
- arthritis
- arthralgia
- eye problems (Sjogren’s syndrome)
- cirrhosis
- hepatocellular cancer
- cryoglobulinaemia
- membranoproliferative glomerulonephritis (–> renal dysfunction)
What might you see on examination in hepatitis C? (2)
- skin rash caused by mixed cryoglobulinaemia –> small vessel vasculitis
- renal dysfunction (due to glomerulonephritis)
What are the risk factors for hepatitis A&E? (8)
- living in/travel to endemic region
- close personal contact with infected person
- MSM
- known foodborne outbreak
- illegal drug use
- homelessness
- immunosuppression
- infected mother (for foetus)
What are some risk factors for hepatitis B&D? (6)
- IV drug use
- unscreened blood/products (including haemodialysis)
- infants of HBeAg/HBsAg-positive mothers
- sexual contact with Hep B carriers
- born in endemic region
- Fx of HBV, hepatocellular carcinoma and/or chronic liver disease
What are some risk factors for hepatitis C? (6)
- IV drug users
- needlestick injury - healthcare workers
- blood transfusions (especially before 1992)
- non-sterile acupuncture
- tattooing
- haemodialysis
What are the general first-line investigations for viral hepatitis? (4)
- LFTs + bilirubin
- urinalysis
- viral serology (diagnostic)
- U&Es
In general, what do LFTs show in viral hepatitis? (5)
Raised:
- AST
- ALT
- ALP (generally not as elevated as AST&ALT)
- bilirubin
- GGT
What would we see in bloods in viral hepatitis? (4)
- high ESR
- low albumin
- high platelets
- high PT in severe liver disease
What might uranalysis show in viral hepatitis? (2)
- positive for bilirubin
- raised urobilinogen
What is the test of choice for diagnosis of hepatitis A?
IgM anti-hepatitis A virus serology
What serology does hepatitis A have? (2)
- anti-hepatitis A IgM present during acute illness, disappears after 3-5 months
- anti-hepatitis A IgG persists indefinitely after infection/vaccination
What serology does hepatitis E have? (2)
- anti-hepatitis E IgM for active infection
- anti-hepatitis E IgG for past infection
What test is generally positive in hepatitis B?
HBsAg positive (surface antigen)
What would you find in acute hepatitis B?
HBsAg positive & IgM anti-HBcAg positive
What would you find in chronic hepatitis B?
HBsAg positive & IgG anti-HBcAg positive
May be HBeAg positive or negative (correlates with severity)
What would you find in hepatitis B cleared?
Anti-HB antibody positive & IgG anti-HBcAg positive
What would you find in hepatitis B vaccinated?
Anti-HB antibody positive and everything else negative (no IgG anti-HBcAg like in hep B cleared)
What is HBeAg in hepatitis B?
Marker of infectivity - higher means more infectious and so more likely to transmit
How do we detect hepatitis D?
IgM or IgG against hepatitis D virus with PCR
What is high in severe cases of hepatitis B/D?
PT = sensitive marker for significant liver damage
How do we detect hepatitis C?
Anti-hepatitis C antibodies + RT-PCR
- IgM = acute
- IgG = past exposure or chronic
What more invasive investigation can be done for viral hepatitis?
- liver biopsy - assess degree of inflammation and liver damage
- percutaneous/transjugular if clotting deranged or ascites present (hepatitis B/D)
- useful for diagnosing cirrhosis (hepatitis C)
What marker can we test for in viral hepatitis?
Alpha-fetoprotein (AFP) for those with hepatitis B/C as high risk of cancer
What are some differential diagnoses for viral hepatitis? (11)
- EBV infection - lymphadenopathy and splenomegaly
- Coxsackie virus - buccal/pharyngeal lesions, hand-foot-and-mouth disease
- CMV infection
- HSV infection - cutaneous ulceration
- biliary atresia - jaundice 0-8wk of age
- autoimmune hepatitis
- alcoholic hepatitis
- ischaemic hepatitis
- drug-induced hepatitis
- A1AT disease
- Wilson’s disease
How do we manage acute viral hepatitis?
Bed rest and supportive, symptomatic treatment (e.g. antipyretics, antiemetics or cholestyramine for severe pruritus)
What can we give for chronic hepatitis B/C? (3)
- interferon alpha (antiviral) - standard or pegylated (increased half-life) - cytokine which augments natural antiviral responses
- hepatitis C: ribavirin (guanosine nucleotide analogue)
- nucleoside/nucleotide analogues (entecavir, adefovir, telbivudine, tenofovir)
What should we screen for in viral hepatitis patients?
HIV
How can we prevent hepatitis A? (4)
- hepatitis A vaccine (no vaccine for hepatitis E)
- safe water
- sanitation
- food hygiene
What are the main principles for treatment of hepatitis A? (2)
- symptomatic management
- avoid alcohol and excess paracetamol
What are indications for antiviral treatment in hepatitis B (low yield)?
- chronic hepatitis (ALT and hepatitis B DNA levels)
- compensated cirrhosis and HBV DNA>2000iu/ml
- decompensated cirrhosis and detectable HBV DNA by PCR
What do we give for chronic hepatitis B?
Interferon alpha (antiviral - cytokine that increases natural antiviral responses)
How do we prevent hepatitis B/D? (4)
- hepatitis B vaccine
- blood screening
- safe sex
- instrument sterilisation
What antivirals can we give for hepatitis C? (2)
- interferon alpha
- ribavirin
How can we prevent hepatitis C? (2 + 1)
- blood screening
- instrument sterilisation
- no vaccine available for hepatitis C
What type of disease is viral hepatitis (A-E)?
Notifiable disease
What types of viral hepatitis is there a vaccine for?
Only hepatitis A&B
- active immunisation with attenuated hepatitis A vaccine offers safe and effective immunity for those travelling to endemic areas and high-risk individuals
- passive immunisation with IM human immunoglobulin effective for short time
What are some complications of viral hepatitis? (7)
- fulminant hepatic failure (especially in pregnant women) - mortality 80%
- cholestatic hepatitis
- post-hepatic syndrome (malaise for months)
- cirrhosis
- hepatocellular carcinoma (NOT hepatitis A/E)
- chronic hepatitis
- extra-hepatic manifestations (rare, hepatitis C): cryoglobulinaemia, AIHA, glomerulonephritis (also in Hep B), leukocytoclastic vasculitis, diabetes, hypothyroidism, skin conditions
What is an extra-hepatic manifestation ONLY seen in hepatitis B?
Polyarteritis nodosa - systemic upset, nodular and ulcerating skin lesions and mononeuritis complex, skin biopsy –> non-granulomatous necrotising vasculitis
What are the most common causes of hepatocellular carcinoma (complication of hepatitis B&C)?
- most common cause worldwide = chronic Hep B
- most common cause in Europe = chronic Hep C
What are some risk factors for hepatocellular carcinoma (complication of hepatitis B&C)? (5)
- liver cirrhosis secondary to Hep B&C
- alcohol
- NAFLD
- A1AT deficiency
- haemochromatosis
How do we investigate hepatocellular carcinoma (complication of hepatitis B&C)? (2)
- raised alpha-fetoprotein (AFP) - useful diagnostic marker
- screening with US and AFP - for people with cirrhosis secondary to Hep B/C, haemochromatosis or alcohol
Describe the prognoses of viral hepatitis. (3)
- hepatitis A&E: usually recover within 3-6 weeks
- hepatitis B&D: 10% become chronic, of these 20-30% develop cirrhosis
- hepatitis C: 80% become chronic, of these 20-30% develop cirrhosis
