HEPATITIS-GI PATHOLOGY {S1}

1. HEPATITIS-GI PATHOLOGY {S1} BY RANJEET RAMAN

2. Overview of hepatitis • ​ Hepatitis defined: inflammation in the liver • ​ Note other causes of hepatitis • ​noninfectious, e.g. alcohol, acetaminophen, other meds, etc. • ​nonviral infectious (various) • ​other viral infectious, e.g. CMV, EBV, HIV, adenovirus

3. Hepatic fibrosis: overgrowth of connective tissue, impairs liver function • ​Cirrhosis: widespread fibrosis and nodule formation • ​Hepatocellular carcinoma: • ​Clinical course of acute hepatitis: exposure incubation prodrome icteric phase convalescence or recovery or persistence ​ - Symptoms and persistence are inversely related; as age increases persistence increases

4. Major differences between hepatitis viruses • HAV, HEV: fecal-oral transmission (due to bile stable Nonenveloped structure), acute, primary cause of jaundice • ​HBV, HCV, HDV: sexual/blood/perinatal transmission, chronic

5. Diagnosis of hepatitis • ​Transaminase levels (indicative of liver dysfunction) • ​IgM antibody (indicative of recent infection) • ​Neutralizing antibodies (indicative of recovery, unless viral particles present) • ​Viral particles, e.g. protein or nucleic acid (indicate of ongoing infection)

6. HAV • ​picornaviruses (+ strand RNA), Nonenveloped, elicits universal neutralizing Ab • ​vaccine protects • ​treatment: none (acute), prevent secondary cases • ​Dx: IgM anti-HAV marks acute infection for 6 months

7. HBV • ​DNA genome that replicates through RT of RNA intermediate (high mutation rate) • ​4 ORFs: S (surface Ag), C (core HBeAg), P (polymerase), X • ​vaccine based on surface Ag • ​treatment: interferon alpha or lamivudine • ​Diagnosis: positive HBsAg and anti-HBc (acute), positive HBsAg and HBeAg (chronic)

8. HDV • ​infectious only in combination with HBV (uses its outer coat) • HCV • ​ single RNA with IRES, high copy number • ​closely related to HIV • ​viral diversity due to rapid turnover and error prone replication • ​treatment: interferon alpha (regulated) and ribavirin

9. HEV • ​increased fatality in pregnant women • ​treatment: none (acute), prevent secondary cases • HFV: fake, based on falsified data • HGV: not causal for hepatitis

10. Viral Hepatitis • Hepatitis can be infectious or non-infectious. • Non-infectious causes include alcohol use and use of Tylenol or other medications. • Infectious causes can be nonviral or viral (CMV, EBV, HIV, Hepatitis viruses). • Hepatitis A is the most common cause of acute hepatitis, followed by HBV.

11. About a month after exposure, jaundice and other symptoms signal the end of incubation ​period and the beginning of active disease. After a period of disease, the virus ​may be eliminated or may persist. • Liver fibrosis is the overgrowth of connective tissue. Liver cirrhosis is widespread ​fibrosis with nodule formation. Cirrhosis suggests hepatic damage.

12. Only HAV and HEV are transmitted fecal-oral, because they are not destroyed by bile salts. • HCV is transmitted in blood, and HBV and HDV are transmitted by blood and sex. • Hepatitis A • Most common cause of acute hepatitis. It is a picornaviruses (plus-strand RNA virus). • Transmitted by the fecal-oral route (same for HEV) because it is stable in bile salts. • Never persists after acute phase (same for HEV).

13. If anti-HAV IgM is high, there was recent acute HAV. IgM is a maker for acute infection. • Hepatitis E is just like Hepatitis A but HEV especially kills pregnant women.

14. Hepatitis B • As with HAV, acute infections of Hepatitis B are marked by a transient rise in IgM. In ​addition, the HBV antigen decreases. In chronic infections, the antigen remains high. • ​Thus, when infectious agents or their nucleic acids are detected, it implies an ​ongoing infection.

15. HBV has an envelope that is digested by bile salts. Very stable in the environment though. • It is a DNA virus but has an RNA intermediate so requires reverse transcriptase. Acts ​like an RNA virus. • S gene is a surface protein antigen. It is what is cloned to make HBV vaccine.

16. Hepatitis D • Totally ineffective and non-infectious without the HBV S-antigen available. So you ​absolutely can’t get Hepatitis D without Hepatitis B. • Hepatitis C • Transmitted almost exclusively by blood. • Does not cause acute infections but usually persists. Highly infectious. • Its genome is extraordinarily tolerant of errors. Rapid turnover, and error-prone replication.

17. HCV has huge genomic instability and diversity, which overcomes vaccines, drugs, and ​immune reactions. • HCV is the most diverse human virus.