Infectious intra-hepatic cholestasis Flashcards
In which patient group is jaundice secondary to bacterial infection more commonly seen?
neonates - can occur with sepsis
In adults what are the key types of infectious causes of intra-hepatic cholestasis, leading to jaundice? 6 main types
- Hepatitis A-E
- CMV
- EBV
- Adenovirus
- Leptospirosis
- Malaria
What are 8 general clinical features of infectious hepatitis?
- malaise and fatigue
- nausea and vomiting
- right upper quadrant pain
- diarrhoea (may have pale stools and dark urine)
- jaundice
- hepatomegaly
- splenomegaly and lymphadenopathy
- liver failure: characterised by hepatic encephalopathy, jaundice, ascites and abnormal clotting
Which infectious hepatitis causes are notifiable disease in the UK?
all infectious hepatitis cases
What are the 3 most common causes of viral hepatitis in the UK?
hepatitis A, B and C
Of the types of viral hepatitis A-E, which cause a viral/chronic picture?
- Hepatitis A: acute
- Hepatitis B: acute and/or chronic
- Hepatitis C: acute ultimately leading to chronic
- Hepatitis D: acute and/or chronic
- Hepatitis E: acute
What are the 2 types of hepatitis which are usually acute only?
A and E (for E: can be chronic in pregnancy or weak immune system)
What is the usual course of hepatitis A?
causes acute liver injury which is usually self-limiting
What type of virus is hepatitis A?
single-stranded RNA virus; enterovirus (picornavirus)
What is the incubation period of hepatitis A?
2-6 weeks
What is the route of transmission of hepatitis A?
faeco-oral
from contaminated water or shelffish
What are hepatitis A epidemics associated with?
overcrowding and poor sanitation; thrives in areas of poor hygiene
When are patients with hepatitis A most infectious?
before the onset of jaundice
What are 3 risk factors for hepatitis A virus?
- Young people most affected
- Travellers, especially to developing countries: South America, Africa, Russia, Asia
- Childcare workers
What are the clinical features of hepatitis A and how do they change with time?
- flu-like symptoms followed by jaundice, pale stools, dark urine, upper right quadrant abdominal pain
- nausea/vomiting, diarrhoea, malaise, fatigue, headache
- hepatomegaly/splenomegaly, lymphadenopathy
What is the only real determinant of hepatitis A disease severity?
increasing age: greatest morbidity and mortality in those over 50 years old
Is there increasd risk of hepatocellular cancer with hepatitis A?
no
What are 6 indications for hepatitis A vaccination?
- people travelling to or going to reside in areas of high or intermediate prevalence, if aged >1 year old
- people with chronic liver disease
- patients with haemophilia
- men who have sex with men
- injecting drug users
- individuals at occupational risk: lab worker, staff of large residential institutions, sewage workers, people who work with primates
How should the hep A vaccine be given?
after initial dose, booster should be given 6-12 months later
What are the diagnostic test for hepatitis A? 2 types
- anti-HAV specific IgM (means current infection), anti-HAV IgG suggests previous infection or vaccination
- Stool culture: virus in faeces for 2 weeks before onset of jaundice and a few days after
What will LFTs shown in hepatitis A?
↑ raised AST, ALT: usually > 1000, ↑ bilirubin
How long does immunity from the hepatitis A vaccine last?
lifelong
What is the management of hepatitis A?
conservative/supportive, usually self-limiting with complete resolution
What type of virus is hepatitis B?
double-stranded DNA hepadnavirus
has outer envelope and lipid core with associated antigens
What type of illness is caused by hepatitis B virus?
acute and/or chronic liver injury; infection is dynamic and changes over time, therefore needs lifelong monitoring. starts out as acute and can develop into chronic in a proportion of patients
In what proportion of patients does hepatitis B infection progress from acute to chronic?
progresses to chronic in 10% of aduls and 90% of infants
What is the most common cause of hepatitis globally?
hepatitis B
In what region of the world are there high prevalence rates of hepatitis B?
sub-Saharan Africa, Asia, Pacific Islands
What is the incubation period of hepatitis B?
60-90 days
What are 3 routes of transmission of hepatitis B virus?
- vaginal/anal intercourse
- transfusion/ infected blood, IVDU
- vertical transmission - in 90% of pregnancies where mother is HBeAg positive
What are the 3 types of antigens of hepatitis B virus?
- HBV surface antigen (HBsAg): outer lipoprotein envelope
- HBV core antigen (HBcAg): internal core which surrounds viral DNA genome
- HBV e antigen (HBeAg): previously used as marker of circulating virus and infectivity
How does acute hepatitis B virus lead to chronic hepatitis B virus?
if immune compettent, virus will be cleared, if not will lead to chronic HBV
What are 2 classes into which chronic hepatitis B virus patients are grouped into?
HBeAg +ve chronic HBV
HBeAg -ve chronic HBV
What are the 3 ways in which HBV and the body react together?
- Immune-tolerant: HBV replicates unchecked and the body acts as if it is unaware of the virus with no immune response, so no liver damage occurs. HBeAg + ve with very high viral load (> 10 8 ). Previously called ‘high infectivity’
- Immune-active: body recognises the virus but mounts an inappropriate immune response so there are fluctuating levels of virus, infectivity and liver inflammation. Can lead to fibrosis, cirrhosis and HCC. HBeAg + ve or − ve. Viral load usually high
- Immune-control: body recognises the virus and controls it, so there are low levels of virus (< 1000), low infectivity and little liver damage. HBeAg –ve. Used to be called ‘low risk carrier’ or ‘inactive’. Low risk for complications
What are 9 groups of patients who should receive immunisation against hepatitis B in the UK?
- all children born: 2, 3 and 4 months of age
- healthcare workers
- IVDUs
- Sex workers
- Close family contacts of individual with hepB
- individuals receiving regular blood transfusions
- CKD patients who may soon require renal replacement therapy
- prisoners
- chronic liver disease patients
What are the antibodies/antigens that indicate acute hepatitis B, chronic hepatitis B and vaccinated against hepatitis B?
- acute hepatitis B: raised IgM to HBcAg, HBsAg detected 3-5 weeks after infection
- previous acute hepatitis B, not a carrier: anti-HBc positive, HBsAg negative
- chronic hepatitis B: anti-HBc positive, HBsAg positive
- vaccinated: anti-HBs positive only
HBsAg = ongoing infection, either acute or chronic if present >6 months
anti-HBc= indicates current or previous hep B infection (acute or chronic), not present if immunised (c=caught)
What is the physioloy of the antibody response to the hepatitis B immunisation?
the vaccine contains HBsAg adsobed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology
adequate response = develop anti-HBs, level rises to >100
What proportion of adults fail to respond or respond poorly to 3 doses of the hepatitis B vaccine?
10-15%
What are 5 risk factors for poor response to the hepatitis B vaccine?
- age over 40 years
- obesity
- smoking
- alcohol excess
- immunosuppression
In which patients is testing for anti-HBs folowign immunisation indicated, and when?
at risk of occupational exposure (healthcare workers), CKD
check 1-4 months after primary immunisation
What are 3 classes of response to the hepatitis B immunisation? What should be done for each result?
- >100: adequate response
- no further testing required, should still receive booster at 5 years
- 10-100: suboptimal response
- one additional vaccine dose should be given
- if immunocompetent no further testing required
- <10: non-responder
- test for current or past infection
- give further vaccine course (i.e. 3 doses again) with testing following
- if still fails to response then HBIG would be required for protection if exposed to the virus
What does the hepatitis B vaccination involve?
3 doses of virus
What does the presence of HBsAg usually imply?
first marker to appear and causes the production of anti-HBs (not immediately present)
normally implies acute disease (present for 1-6 months)
What does anti-HBs imply?
immunity, either through exposure or immunisation
negative in chronic disease
Waht does anti-HBc imply?
previous or current infection, negative in immunisation
IgM anti-HBc appears during acute or recent hep B and present for 6 months. IgG anti-HBc persists
What is HbeAg a marker of?
results from breakdown of core antigen from infected liver cells - marker of infectivity
What are 3 aspects of treatment of hepatitis B virus?
- pegylated interferon-alpha - precipitates seroconversion
- tenofovir, entecavir, telbivudine - inhibit HBV replication
- second line alternatives
- transplantation - end-stage cirrhosis or HCC
What is the mechanism of action of pegylated interferon-alpha for treating hepatitis B?
reduces viral replication, precipitates serovoncersion.
What must be given with transplantation for hepatitis B with end-stage cirrhosis or HCC?
HBV Immunoglobulin (HBiG) to prevent recurrence in graft
What are 4 investigations to consider in hepatitis B?
- LFTs: AST, ALT high in acute infection (may be normal/slightly raised in chronic infection)
- Viral load (HBV DNA)
- Serology: antigens/antibodies
- Liver biopsy: assess degree of inflammation and fibrosis to decide on phase of disease and guide treatment
What will LFTs show in hepatitis B infection?
high in acute infection, may be normal/slightly raised in chronic infection
What are the clinical features of hepatitis B infection?
- jaundice, fever, malaise, dark urine, pale stool
- fulminant liver failure with decompensation: ascites, encephalopathy
- arthritis/arthralgia, rash
- chronic: asymptomatic, or symptomatic and complicatoins of cirrhosis and portal hypertension, can present with HCC
- often subclinical in children
What should be done to babies born to mothers who are chronically infected with hepatitis B/ have acute hep B in pregnancy?
complete course of vaccination + hepatitis B immunoglobulin
Can hepatitis B be transmitted via breastfeeding?
no (but HIV can)
What type of virus is hepatitis C?
RNA flavivirus. 6 major genotypes, 1 and 3 most common in UK
What is the incubation period of hepatitis C?
6-9 weeks
What type of course of illness can hepatitis C cause?
Which hepatitis C genotype is associated with longer treatment and worse prognosis?
genotype 1
How is hepatitis C transmitted?
exchange of blood and bodily fluids
- IVDU
- blood transfusion
- haemodialysis
- sexual transmission
- needlestick injuries
- perinatal infection from infected mother
Is there a vaccination available for hepatitis C?
no
What are the clinical features of hepatitis C?
most infections asymptomatic; patients with chronic infection have persistently high LFTs and cirrhosis develops in 20-30%
What proportion of patients with hepatitis C clear the virus?
15-25% clear the virus
What are 6 complications of hepatitis B infection?
- chronic hepatitis - ground glass hepatocytes on light microscopy
- fulminant liver failure
- hepatocellular carcinoma
- glomerulonephritis
- polyarteritis nodosa
- cryoglobulinaemia
In what regions in hepatitis C more common?
Egypt, S Europe, Africa
What are 8 investigations which can be performed in hepatitis C?
- LFTs: raised ALT and AST
- INR
- Alpha-fetoprotein: often mildly raised
- HCV antibody, HCV RNA
- HCV genotype
- US/CT liver
- Transient elastography: non-invasive testing liver stiffness
- Liver biopsy: shows extent of fibrosis/cirrhosis
What are 5 aspects of the management of hepatitis C virus?
- Initially symptomatic treatment in early stages
- Interferon-alpha (usually pegylated)
- Protease inhibitors combination (daclatasvir + sofosbuvir or sofosbuvir + simprevir) with or without ribavirin
- Manage underlying cirrhosis
- Liver transplant
What proportion of patients will develop clinical features of hepatitis C after exposure to the virus?
30% e.g. transient rise in aminotrasferases/ jaundice, fatigue, arthralgia
What is the investigation of choice to diagnose hepatitis C infection?
HCV RNA
What is the definition of chronic hepatitis C virus?
HCV RNA in blood for 6 months
What are 7 potential complications of chronic hepatitis C?
- Rheumatological problems: arthralgia, arthritis
- Eye problems: Sjogren’s syndrome
- Cirrhosis
- Hepatocellular cancer
- Cryoglobinaemia: type II (mixed monoclonal and polyclonal)
- Porphyria cutanea tarda (PCT)
- Membranoproliferative glomerulonephritis
What is the aim of treatment of hepatitis C virus?
sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy
What are 3 side effects of ribavirin (treatment of hep C)?
- Haemolytic anaemia
- Cough
- Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
What are 5 side effects of interferon alpha?
- Flu-like symptosm
- Depression
- Fatigue
- Leukopenia
- Thrombocytopenia
What type of virus is hepatitis D?
RNA (delta) virus; a virus cannot replicate alone, being dependent on HBV
What is the likelihood of chronic infection with hepatitis D virus?
high risk of chronic infection
How is hepatitis D transmitted?
parenterally, in similar fashion to hepatitis B (exchange of bodily fluids) and patients may be infected with hepatitis B and D at the same time
- parenteral
- sexual less efficient than HBV
- vertical transmission rare
What are 2 ways that a patient may be infected with both hepatitis B and D?
- co-infection: hepatitis B and D infection at same time
- superinfection: hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection
In which regions is hepatitis D common?
S Italy, N Africa, Middle East
How is a diagnosis of hepatitis D made?
anti-D IgM in acute infection, anti-D IgG in chronic infection
HDV RNA to demonstrate active infection
What are 3 high risks associated with hepatitis D+B superinfection?
- Fulminant hepatitis
- Chronic hepatitis status
- Cirrhosis
What are 3 aspects of the treatment of hepatitis D?
- Pegylated interferon alpha
- Supportive
- Treat underlying hepatitis B
How does infection with hepatitis D rather than hepatitis B alone affect prognosis?
faster progression to fibrosis and cirrhosis than with hepatitis B alone
What type of virus is hepatitis E?
single stranded RNA hepevirus, resembles hepatitis A virus
How is hepatitis E spread?
faecal-oral route
What is the incubation period of hepatitis E?
3-8 weeks
In which areas in hepatitis E common?
Central and South-East Asia, Norh and West Africa, Mexico
What is a difference in the clinical effects of hepatitis A vs hepatitis E?
hepatitis E carries significant mortality during pregnancy
Does hepatitis E cause chronic disease?
no (rarely)
Does hepatitis E cause increased risk of hepatocellular cancer?
no
Is there a vaccine for hepatitis E?
currently in development but not yet in widespread use
How is a diagnosis of hepatitis E made?
anti-HEV IgM in acute, anti-HEV IgG if previous exposure
What is the treatment of hepatitis A?
same for A - supportive, usually self-limiting
