Viral Hepatitis Flashcards
1
Q
Hepatitis A
A
- Cause of:
- Infectious hepatitis
- Epidemic hepatitis
- Epidemic jaundice
- Type A hepatitis
- Transmission is faeco-oral
- Close personal contact
- Household, child day care, sexual
- Contaminated food and water
- Food handlers, raw shellfish
- Blood exposure - rare, IVDU or transfusion (now screened for)
- Close personal contact
- Virus present in stool for up to 3 weeks prior to onset of jaundice
2
Q
Hepatitis A - Virology
A
- Key virological features:
- First identified by electron microscopy 1973
- RNA Picornavirus; hepatovirus
- No envelope
- Resistant to degradation
- ‘Survives’ 70C for 10 mins and pH 1 room temp for 2 hrs
- Single serotype worldwide
3
Q
Hepatitis A - Clinical Features
A
- Spectrum of disease from aymptomatic infection to acute liver failure
- Many asymptomatic infections - age related (children more likely to be aymptomatic)
- Does not cause chronic infection
- Total anitbody to HAV develops in response to infection and confers lifelong immunity
- Four clinical phases:
- Incubation/ pre-clinical, 10-50 days (well, but infectious)
- Prodromal/ pre-icteric, few days to 10 days, flu like illness, loss appetite
- Icteric phase, fever, jaundice (pale stool & dark urine), liver enlargement and tenderness, anorexia, vomiting, fatigue, lasting 1-3 weeks
- Convalescence
4
Q
Hepatitis A - Rare Complications
A
- Fulminant hepatitis
- Cholestatis
- Relapsing hepatitis (3-20% cases, but not after 12 months)
5
Q
Hepatitis A - Pathogenesis
A
- Jaundice probably due to immune mediated T lymphocyte destruction of hepatocytes
- Not clear how this is linked to age specific rates jaundice (increases with age)
- Fulminant hepatitis is fatal in up to 60% cases
- Death inevitable when >80% hepatocytes killed
- Worse prognosis if underlying liver disease
- Chronic HBV, HCV
6
Q
Hepatitis A - Diagnosis
A
- Clinical
- Biochemical features
- Epidemiological clues (age, risk groups, travel, vaccine)
- Difficult
- Laboratory
- Serology
- Detection of IgM
7
Q
Acute Hepatitis A - Managment
A
- Supportive, self-limited infection
- No antivirals
- Check liver function, clotting, U&Es
- Vomiting, dehydration, altered consciousness bad signs-admit
- Transplant for acute liver failure
- Notifiable disease
8
Q
Hepatitis A - Prevention
A
- Avoid risk
- Hygiene (hand washing)
- Clean water sources
- Travel
- Immunisation
- Active: Hepatitis A vaccine (pre and post exposure)
- Cell culture adapted virus, formalin inactivated
- Safe, highly immunogenic, highly effective
- Passive: Human normal immunoglobulin (HNIG) - post exposure within 14 days
- Active: Hepatitis A vaccine (pre and post exposure)
9
Q
Hepatitis A - Groups Recommended for Hepatitis A Vaccine
A
- Injecting drug users
- International travelers to endemic areas
- Persons who have clotting factor disorders
- Persons with chronic liver disease
- Consider in men who have sex with men
10
Q
Hepatitis B
A
- Previously known as serum hepatitis
- Causes acute, resolved infection
- Can lead to chronic infection
- Huge global burden of infection and disease
- Transmission = typical blood borne virus
- Sexual
- Mother to child - signigicant in endemic regions
- Needle sharing
- Blood products
11
Q
Hepatitis B - Virology
A
- Hepadnavirus
- ds DNA, enveloped
- Relatively easily degraded
- Several genotypes
- Geographically restricted and can influence treatment outcome
12
Q
Hepatitis B - Clinical Features
A
- Acute and chronic infection
- Acute resolved:
- Asymptomatic
- Non-specific illness
- Hepatitis/ jaundice
- Due to immune response
- Chronic:
- Evidence of chronic liver disease
- ==> to cirrhosis and hepatocellular carcinoma (HCC)
- Evidence of chronic liver disease
- Incubation period average 60-90 days (45-180)
- Outcome of infection linked to age at infection/immune response
- Virtually all infants and children asymptomatic
- But much more likely to become chronic carriers
- Up to 50% adults asymptomatic, especially likely if HIV infected
- Acute case-fatality rate (overall) 0.5%-1%
- Virtually all infants and children asymptomatic
- If symptomatic, prodrome, icteric phase like HAV
- May see signs of chronic liver disease
13
Q
Hepatitis B - Complications
A
- Premature mortality fro Cirrhosis and HCC 15-25%
- Worldwide HBV infection accounts for:
- 30% of all cases of cirrhosis
- 53% of al hepatocellular carcinoma cases
14
Q
Hepatitis B - Pathogenesis
A
- Chronic vs. acute resolved
- Feature of the immune response
- Affected by:
- Maturity
- Immunosuppression
- HLA type
- HBV DNA persists in the host cell nucleus as cccDNA
- Can also integrate into host chromosome
- Mechanism of hepatocellular carcinoma unclear
15
Q
Hepatitis B - Diagnosis
A
- Clinical and epidemiological clues
- Serology:
- Hepatitis B surface antigen (HBsAg) ==> Infected, acute or chronic
- Hepatitis B core IgM antibody (Anti-HBc IgM) ==> Recent infection (usually)
- Hepatitis B core total antibody (Anti-HBc) ==> Infected at some time, may have resolved or be chronic
- Hepatitis B e antigen (HBeAg) ==> Infected, acute or chronic with high levels of virus
- Hepatitis B e antibody (Anti-HBe) ==> Infected at some time. If chronic, usually low levels of virus
- Hepatitis B surface antibody (Anti-HBs) ==> Recovery from natural infection or vaccine response
- Hepatitis B DNA (HBV DNA) ==> Partly defines need for therapy and infectivity
16
Q
Acute Hepatitis B - Management
A
- Supportive, antivirals not usually given
- Check clotting, electrolytes
- Transplant for acute liver failure
- Counsel regarding transmission
- Screen for other bloodborne viruses, STDs
- Notifiable disease
- Trace, test, and immunise relevant contacts
17
Q
Chronic Hepatitis B
A
- Defined as on-going infection for >6 months
- Who to treat?
- Guidelines evolving
- Basically patients with viral replication causing active hepatitis:
- e antigen positive + abnormal ALT
- e antigen negative + abnormal LFT + HBV DNA >2,000 IU/mL
- Other factors: coinfection HCV, HIV, cirrhosis, pregnant, starting immunosuppressive drugs
- Basically patients with viral replication causing active hepatitis:
- Guidelines evolving
18
Q
Chronic Hepatitis B - Therapy Goals
A
- HBV infection cannot currently be completely eliminated or “cured”
- The clinical goal of HBV treatment:
- Prevention or reversal of complications and death resulting from advancing severity of liver disease
- Achieved by reducing HBV DNA levels
- Prevention or reversal of complications and death resulting from advancing severity of liver disease
- Therapies designed to suppress HBV replication are associated with biochemical remission and prevention further liver injury
- Ideally clear HBsAg, or at least seroconvert from e Ag to e Ab
19
Q
Hepatitis B Antiviral Therapy
A
- Immunomodulators:
- Interferon alpha (alpha 2b, pegylated 2a)
- Response rate 60% at best
- Side effects
- Nucleoside analogues
- Lamivudine, adefovir, entecavir, tenofovir
- Effective rapid reduction in HBV DNA
- Antiviral resistance may develop
- Especially to lamivudine
- 20% at one yr, 60% at 5 yrs
- Consider combination therapy/sequential therapy
- Prolonged or life long therapy
- Current first line treatments = entecavir, tenofovir, or pegylated IFN - based on disease features and patient choice
20
Q
Hepatitis B - Prevention
A
- Avoid/ reduce risk
- Safe sex, needle exchange, infection control
- Screening:
- Blood products, high risk groups, pregnancy
- Vaccine
- Primary prevention, post exposure
- Universal or targeted
- Active
- Currently recombinant HBsAg made in yeast/bacteria
- Not live and very safe
- Highly immunogenic and protective
- Protection continues even after antibody levels decline
- Passive (HBIG)
- Treatment of infected
21
Q
Hepatitis C - Epidemiology
A
- Major public health problem
- Estimates of around 200,000 people aged 15-59 years with chronic infection in England (0.3% or population)
- Majority undiagnosed
- Injecting drug users are the key risk group - 90% of newly acquired infections
- Worldwide accounts for:
- 27% of cases of liver cirrhosis
- 25% of hepatocellular carcinoma
- Rarely ==> death from acute liver failure
- Major indication for liver transplant
22
Q
Hepatitis C - Transmission
A
- Blood-borne virus
- Percutaneous:
- Injecting drug use
- Clotting factors before viral inactivation/recombinant products
- Transfusion/transplantation
- Contaminated hospital equipment
- Occupational needlestick (risk 1.8% from positive source)
- Permucosal
- Perinatal (up to 5%, no association with breastfeeding)
- Sexual (<1% risk discordant long term couples, higher MSM)
- 10% have no clear risk factor, temporal link lost as often present late in illness
23
Q
Hepatitis C - Virology
A
- Flavivirus, Hepacivirus
- Positive single stranded RNA
- Enveloped
- Many different genotypes
- Distributed geographically
- Influence treatment response
24
Q
Hepatitis C - Clinical Features
A
- Acute resolved infection occurs, but uncommon
- If acute icteric hepatitis occurs it is similar to that seen in HAV
- Majority (>80%) have asymptomatic acute infection
- Chronic infection common
- Natural history:
- Incubation 6-7 weeks ==>
- Acute HCV (jaundice rare) ==>
- Resolve 15%
- Chronic HCV 85% ==>
- Stable 80%
- Cirrhosis 20% ==>
- Slowly progressive 75%
- HCC/liver failure 25%:
- Ascites
- Variceal haemmorhage
- Jaundice
- Encephalopathy
- Acute HCV (jaundice rare) ==>
- Incubation 6-7 weeks ==>
25
Hepatitis C - Pathogenesis
* Chronic or acute resolved
* Poorly understood
* Affected by:
* Immunosuppression
* HLA type
* Viral genotype
* Mechanism of cirrhosis and HCC:
* Chronic inflammation
* Immune mediated cytotoxicity
* High cell replacement rate
* Higher risk of severe fibrosis:
* Increased alcohol intake
* Age \> 40 years at time of infection
* HIV co-infection
* Male gender
* Chronic HBV co-infection
26
Hepatitis C - Diagnosis
* Usually picked up by screening risk groups or contacts or as part of liver disease work up
* Serology - antibody or nucleic acid (RNA)
* Seroconversion window period up to 3 months
* Some patients never make detectable antibody - especially if immunosuppressed
27
Management of Hepatitis C - General
* Counsel on routes of transmission
* Explain long-term prognosis
* Avoid alcohol
28
Management of Hepatitis C - Acute
* Difficult to spot - usually asymptomatic
* High dose IFN-alpha may reduce rate of chronicity
* Otherwise supportive - as for HAV
* Notifiable
29
Management of Hepatitis C - Chronic
* Assessment to include LFT, symptoms, liver biopsy, counsel about alcohol
* Treat all those with moderate or worse disease - assessed by:
* Biopsy
* Non-invasive tests (fibroscan, biochemical marker patterns)
* Immunise against HAV, HBV
* Antiviral therapy
* Goal is to clear HCV RNA
* A sustained virological response (SVR) is associated with greatly reduced progression to cirrhosis
* SVR is HCV RNA negative 6 months after stopping antivirals
* 5 yr rate cirrhosis with SVR 0% vs 13% without
* Combination antiviral therapy
* *Interferon alpha* and *ribavirin* achieve greater response than single agents
* *Pegylated interferon* and *ribavirin* can clear virus in up to 80% non-genotype 1 and 50% genotype 1
* Less effective in IL28 polymorphism
* Side effects and adherence issues - reduce efficacy
* New Drugs:
* Protease inhibitors - *Telaprevir, Boceprevir - *effective against genotype 1
* Polymerase inhibitors - not genotype specific
30
Hepatitis C - Virology Response
* Important to monitor response to therapy and adjust treatment course accordingly
* Various types of supoptimal response:
* Null response = minimal changes in HCV RNA compared with baseline during the first few months of treatment
* Partial response = HCV RNA decreases by ≥ 2 log10 copies/mL from baseline but never declines below the limit of detection
* Breakthrough = patients initially achieve HCV RNA levels below the limit of detection but eventually experience an increase in HCV RNA on treatment to levels comparable to those observed at baseline
* Relapse = undetectable HCV RNA for many months, including through the end of treatment, but detectable HCV RNA in the blood soon after treatment is discontinued
31
Hepatitis C - Prevention
* Risk reduction and counselling
* e.g. Needle exchanges
* Screen and test donors
* Virus inactivation of plasma-derived products
* Safe injection and infection control practices
* No vaccine
32
Hepatitis D - Transmission/Clinical Features
* Blood borne virus:
* Percutaneous exposure
* IVDU
* Permucosal exposure
* Sexual contact
* Satellite virus as can only propagate in the presecence of Hepatitis B virus
* Distinguished by production of delta antigen
* Coinfection = simultaneous transmission with HBB ==\>
* Severe acute disease
* Lower risk of chronic infection
* Superinfection = infection on top of chronic HBV infection or HBV carrier state ==\>
* Usually develop chronic HDV infection
* High risk of severe chronic liver disease
33
Hepatitis D - Prevention
* HBV-HDV Coinfection:
* Pre or postexposure prophylaxis to prevent HBV infection
* HBV-HDV Superinfection:
* Education to reduce risk behaviour among persons with chronic HBV infection
34
Hepatis E - Transmission
* Outbreaks typically associated with contaminated water supply/rainy season
* Refugee camps
* Virus in stool during incubation period and acute phase illness
* Association with eating undercooked pork products, shellfish
* Person to person rates low
* Viraemic phase indicates potential for blood-borne route (rare)
* Transplacental (*in-utero*) described
35
Hepatitis E - Epidemiology
* HEV causes large outbreaks of hepatitis in many parts of the world and sporadic cases probably worldwide
* \>50% acute viral hepatitis in epidemic regions
* Clinico-epidemiological features:
* UK cases imported and endemic
* UK typical patient profile is male, over age 50yrs
* UK indigenous HEV probably more common than HAV
* Zoonosis? - endemic in pigs
* High mortality in late pregnancy (up to 20%)
36
Hepatitis E - Clinical Features
* No chronic infection in immunocompetent (rare even in immunocompromised)
* Incubation:
* Mean 40 days (15-60)
* Spectrum:
* Asymptomatic ==\> acute liver failure
* In epidemic regions:
* Symptomatic cases typically occur in 15-40 year age group
* Infection of children occurs but more often asymptomatic
* Typical natural history similar to hepatitis A, but HEV more severe:
* Prodrome 1-7 days ==\>
* Icteric phase
* Resolution 2-6 weeks
* Mortality 0.5-4% (15-25% late pregnancy)
37
Hepatitis E - Virology
* Genome first characterised in 1990
* Family Hepeviridae, genus Hepevirus, single serotype
* Single stranded positive sense RNA, no envelope
* Moderately stable
* Four major genetic groups (genotypes) - geographically restricted:
* 1- India, Pakistan, China, N Africa
* 2- Mexico
* 3- US, Europe, pigs
* 4- China, Taiwan
38
Hepatitis E - Diagnosis
* (UK) Suspect on basis of exposure and exclusion of other causes
* Serology:
* HEV IgG/IgM
39
Hepatitis E - Management
* Supportive only
* Check LFT, clotting, UE
* Assess for signs of encephalopathy, dehydration
* No antivirals available
* Liver transplant for fulminant hepatitis
* Notifiable
40
Hepatitis E - Prevention
* Avoid:
* Drinking water (and ice) of unknown purity
* Uncooked shellfish/meats
* Uncooked fruit/vegetables not peeled or prepared by traveller
* Vaccine
* New vaccine produced in China
