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Toronto Notes 2019 Liver
Complications
• cholestasis(mostcommonlyassociatedwithHAVinfection)
• hepatocellularnecrosis:AST,ALT>10-20xnormal,ALPandbilirubinminimallyincreased,increased
Gastroenterology G29
cholestasis
Hepatitis A Virus
• RNAvirus
• fecal-oraltransmission;incubationperiod4-6wk
• diagnosedbyelevatedtransaminases,positiveanti-HAVIgM
• inchildren:characteristicallyasymptomatic
• inadults:fatigue,nausea,arthralgia,fever,jaundice
• can cause acute liver failure and subsequent death (<1-5%)
• canrelapse(rarely),butneverbecomeschronic
DDx for Hepatitis
• Viral infection
• Alcohol
• Drugs
• Immune-mediated • Toxins
Causes of Elevated Serum Transaminases in Chronic Hepatitis B
• Ongoing immune-mediated liver injury
without immune control of HBV (HBeAg
positive)
• Immune escape (anti-HBe positive)
• Reactivation, seroconversion (conversion
from anti-HBe to HBeAg)
• Hepatitis D
• Heptocellular carcinoma
• Other liver insult (fatty liver, alcohol, drugs,
hepatitis A)
Risk Factors for Progression
• EtOH
• HIV coinfection
• Old age at diagnosis
In acute hepatitis B, HDV coinfection increases severity of hepatitis but does
not increase risk of progression to chronic hepatitis. However in the context of chronic hepatitis B, superinfection with HDV increases progression to cirrhosis
Without treatment, 8-20% of those with ongoing immunoactive chronic hepatitis can develop cirrhosis within 5 yr. In contrast, those in the immune tolerant phase (with extremely high HBV-DNA levels) are at minimal risk for liver fibrosis as they do not have immune-mediated liver injury
Risk of hepatocellular carcinoma in HBV increases with increasing age, which is likely a surrogate for increasing liver fibrosis/ cirrhosis, and serum HBV-DNA
Risk of hepatocellular carcinoma in HCV increases only after cirrhosis develops
HCV (and HBV) treatment lowers the risk of hepatocellular carcinoma
Hepatitis B Virus
Table 15. Hepatitis B Serology
HBsAg Anti-HBs
HBeAg Anti-HBe Anti-HBc
Liver Enzymes
ALT, AST may or may not be elevated
ALT, AST may or may not be normal
Acute HBV Chronic (e-Ag
positive) HBV (generally high HBV DNA)
Chronic (e-Ag negative) HBV (generally low HBV DNA)
Resolved Infection
Immunization
+ –
+ –
+ –
– ±
– +
+ – + –
– +
– ± – –
IgM IgG
IgG
IgG –
Symptoms
ALT
Anti-HBs
Anti-HBc IgG
Anti-HBc IgM
HBeAg
Anti-HBe
HBsAg
1 2 3 4 5 6 12 24 Months after inoculation
Figure 11. Time course of acute hepatitis B infection
Epidemiology
• 4phasesofchronichepatitisB:notallcarrierswillgothroughall4phases,butallcarrierswillhave positive HBsAg
1. immune tolerance: extremely high HBV-DNA (>20,000 IU/mL), HBeAg positive, but normal ALT/ AST; due to little immune control and minimal immune-mediated liver damage; characteristic of perinatal infection (or ‘incubation period’ in adult with newly-acquired HBV)
2. immune clearance (or immunoactive): HBV-DNA levels (>20,000 IU/mL), HBeAg positive; due to immune attack on the virus and immune-mediated liver damage; characterized by progressive disease without treatment and increasing liver fibrosis (sometimes progressing to cirrhosis and/or hepatocellular carcinoma); likely to benefit from treatment
3. inactive carrier (immune control): lower HBV-DNA (<2,000 IU/mL), HBeAg negative, anti-HBe positive, ALT/AST normal; due to immune control without immune-mediated liver damage; risk of reactivation to phase 2 (clinically resembles acute hepatitis B), especially with immunosuppression e.g. corticosteroids or chemotherapy
4. HBeAg-negative chronic hepatitis (immune escape) (“core or precore mutant”): elevated HBV- DNA (>2,000 IU/mL), HBeAg negative because of pre-core or core promoter gene mutation, anti- HBe positive, ALT/AST high; characterized by progressive disease without treatment and increasing liver fibrosis (sometimes progressing to cirrhosis and/or hepatocellular carcinoma); likely to benefit from treatment