Viral hepatitis Flashcards
Describe viral hepatitis
- Liver predominant site of replication (hepatotropism)
- Causes inflammation and hepatocyte injury (hepatitis – see [[Gastroenterology - Lecture 5]])
- HBV (and HDV) & HCV often evade immune clearance
- Chronic hepatitis means infection ≥ 6 mo - can lead to cirrhosis, HCC
- HCV interacts with alcohol, obesity (risk factors for fatty liver – S. Chitturi lecture)
- Increases incidence of type 2 diabetes
- Increases cirrhosis and HCC risk (synergistically) - see also [[Gastroenterology - Lecture 8#Interactive Liver Toxicity]]
List and briefly describe the hepatitis viruses
Enteral Viruses
- HAV
- RNA virus, non-enveloped
- HEV
- RNA, calicivirus
Blood-borne Viruses (blood/serum, body fluids)**
- HBV
- DNA, enveloped (hepadnavirus)
- HCV
- RNA, flavivirus (hepacivirus), enveloped
- HDV (delta)
- RNA, incomplete (viroid)
** * Sexual transmission common for HBV, rare for HCV
Describe acute hepatitis
Irrespective of etiology (viral, autoimmune, drug-induced), acute hepatitis causes:
- Anorexia (profound, distaste for smoking)
- Nausea
- Vomiting (if repeated, consider onset of liver failure. Shouldn’t be too frequent otherwise)
- Malaise and fatigue; low grade fever (HAV)/not rigors, sore throat/headache (suggests EBV- a common misidentified diagnosis)
- Dark urine (bilirubinuria - confirm by dipstick)
- Jaundice common (not always)
- Tender liver (RUQ pain rare)–> more likely to be biliary pathology eg stones, tract infections
Describe acute hepatitis findings
history, labs
- Contact history (enteral; blood contact/IDU; sexual)
- LFTs: ALT >500 IU/L (ie 5-10 X ULN) - recall that in alcohol hepatitis this can be normal; should be NO leukocytosis
- Hepatitis serology:
- **IgM-anti-HAV
- **HBsAg
- **Anti-HCV
- If travel to endemic region and A/B/C not detected: anti-HEV
- Hepatitis virology (HCV RNA by RT-PCR): if suspect HCV but anti-HCV not detected (see lecture on hepatitis C by S. Walker)
List some differentials for acute hepatitis
Other Viruses (rarely other organisms):
- EBV (mononucleosis), CMV
- H simplex
- HIV, parvovirus
- Q fever/bacterial (rare)
- Yet-to-be characterised (?adenovirus, ?post-SARS-CoV-2 cases of severe acute hepatitis in children {10% liver transplantation} recently observed, not yet fully reported)
Hepatotoxicity and Hepatic Drug Reactions (not rare!)
- (DILI = drug-induced liver injury]
- Paracetamol poisoning (ALT very high)
- Drug-induced “hepatitis” (>300 drugs), eg amoxicillin/clavulanic acid (Augmentin), isoniazid, body-building agents, herbal meds…
Liver Diseases That Are More Usually Chronic:
- Hepatitis B flare (potentially lethal!)
- Autoimmune hepatitis (25% cases)
- Wilson’s disease (children, young adults)
- Alcoholic hepatitis (history, features of chronic liver disease)
- Non-alcoholic steatohepatitis (NASH)
Acute Cholecystitis: Acute Biliary Obstruction/Cholangitis; Liver Abscess
- Pain, fever/rigor, leucocytosis, Murphy’s sign
- Ischemic “hepatitis”: heart failure; shock (ischemia-reperfusion injury)
- Common in hospitals/ICU, ALT/AST»_space;1000, transient (back to normal in 24-72h)
Describe HAV
- Simple enteric virus infection (fecal contamination)
- Often asymptomatic, especially in children
- Severity increases with age (true of many viral infections)
- Incubation 3-6 weeks
- 7-10 days after onset of jaundice, feces no longer infectious
DEscribe hepatitis A diagnosis and epi
Diagnostic Test:
- IgM anti-HAV
- IgG anti-HAV = past infection (NB, labs report “total” antibody and IgM)
Epidemiology:
- Depends on economic development (poor sanitation)
- Mini-epidemics (camps, Eastern suburbs Sydney- likely linked to sexual practices)
- Contaminated hands
- Food-borne (shell-fish; fecal contamination strawberries)
- Sexual spread confined to ano-oral behaviours
List outcomes of Hep A
- Complete recovery in >99%
- Acute (fulminant) hepatic failure, rare
- 0.2% young adults
- 2% elderly
- Relapse or prolonged cholestasis 5-10%
- Chronic infection (carrier state) does not exist
- Lasting immunity indicated by IgG anti-HAV
- Can have persistent pruritus or jaundice for 6-8 wks post infection
Describe HAV vaccination
- Heat-inactivated preparations live attenuated virus
- Two injections over 6 months
- Safe, relatively expensive
- Cost-effective only for community outbreaks
- Combined HAV and HBV vaccines (“Combivax”) useful for selected indications (cirrhosis, chronic HCV, occupation, lifestyle, travel?)
Describe HEV, hepE, and prevention
HEV
- Enteric spread; waterborne
- Sporadic cases and epidemics (historically have been huge)
- Western and southern China (Hong Kong), Indian subcontinent, SE Asia, middle-east, Mexico
- Travel-related acute hepatitis (Hong Kong, SE Asia, central and south America)
- North America, Japan, Australia; food-borne (wild pigs, deer liver) – different strain of HEV, may be less severe; chronic infections among immunosuppressed have been recognised
Hepatitis E
- Acute hepatitis, often severe - particularly in pregnancy (acute liver failure in India)
- Diagnosis: anti-HEV (reference laboratory – we don’t test for HEV unless clear risk factor and other viruses not detected)
- Not usually chronic, but infected persons may continue to shed/spread virus up to 10 weeks
Prevention
- Vaccine developed in China (2012), efficacy demonstrated recently
- Travel precautions:
- Never use local water!!
- Avoid uncooked vegetables
Describe HepB structure and nomenclature esp. of antibodies
Hepatitis B Virus Structure and Nomenclature
- HBsAg (surface antigen)
- HBe antigen (HBeAg – part of viral core) is derived from core- not really reliable indicator of past/active infection
- HBV DNA (Incomplete or covalently-closed circular [cccDNA])
HBV Lexicon
- *HBsAg- the antibody to which is anti-HBs, is most useful for assessing acute or chronic hepatitis
- [HBcAg], the antibody to which is anti-HBc, also useful for assessing acute or chronic hepatitis
- HBeAg, corresponsing antibody is anti-HBe, not really used in clinical practice
- **HBV DNA
- **Essential to assess chronic HBV infection
Describe HBV
- HepaDNAvirus (hosts - duck, woodchuck, primates)
- Replicates via RNA template (reverse transcriptase – like HIV)
- Causes acute or chronic hepatitis
- **Liver elaborates HBsAg far in excess of whole virions
- Common mutations can give rise to HBeAg negative serology (previously regarded as “non-infectious”, “healthy carrier”)
- Serum HBV DNA titre (viral load) is key marker of replication
Describe possible HBV serological manifestations
Inapparent Infection with Recovery
- HBsAg –
- Anti-HBc + - always present in someone who has been infected
- Anti-HBs + (after vaccination, only positive test; decline in titre over 3-7 years - often undetectable)
Acute Hepatitis B (acute liver failure ~1%)
- HBsAg + (Anti-HBc + as well)
- HBeAg +
- HBV DNA very high (not needed for diagnosis)
Chronic HBV Infection (>6 mo)
Chronic Hepatitis B
- May be HBeAg positive or negative (latter more common - *genotypes D, E, C)
- ALT often raised (not always) – may be intermittent increases, with “flares” of ALT>5x ULN spontaneous or iatrogenic immune modulation (may be fatal)
- HBV DNA > 10,000 IU/mL
- Cases may already have cirrhosis
- HCC: 80% cases have cirrhosis (HCC can occur in non-cirrhotic liver with chronic hepatitis B, especially in African, Melanesian, Asian men]
Note: The clinical course of chronic HBV infection is strongly determined by the host immune response, and several stages are often described (see additional slide, but note - not all are reliable or clinically useful; they do not guide my thinking so I generally avoid mention of them except for the phase of immune tolerance in childhood: high viral load and normal ALT)
*Ethnic distribution: Many genotypes (A, D in Europe; B, C Asia; G, H in Eskimos and South America - ancient migration?)
Describe global burden of HBV, and who is/has been at risk
- 350 million worldwide
- Ninth leading cause of death; HCC 2nd cause of cancer death – rapidly rising in Australia
- Nearly 75% Asian
- 90-150,000 in Australia (reflects birth of parents)
- Indigenous Australians born before ~1990
Who is/has been at risk of HBV infection?
- Babies and young children: > 90% chronic, very difficult to eradicate
- Vertical spread
- Newborn of HBsAg positive mothers
- at time of birth
- during last trimester
- Horizontal spread
- Children-children under age 3 years
- Adults: ~3% chronic
- Multiple sexual partners
- Healthcare workers
- Recipients of blood products/transplants (nosocomial spread)
- Injection drug users
- Prisoners, other institutionalised persons
Describe HBV vaccination
- Purified preparation of HBsAg (genetically engineered)
- Safe
- 96% humoral immunity [4% do not respond; remain at risk]
- > 90% reduction of acute hepatitis B
- Lowers rate of HBsAg + in endemic countries (Taiwan, Malaysia, China/Hong Kong, Korea etc) to <1%
- Reduces rate of HCC (Taiwan, Hong Kong for young adults)- ie long term sequelae also reduced
- Less efficacious in elderly, renal failure, obese (use deltoid)
