Hepatitis B is endemic in Thailand, with a prevalence of 8%, and is typically transmitted vertically, sexually, or through blood exposure. The document outlines epidemiology, clinical manifestations including acute and chronic forms, viral markers and their interpretations, natural history including progression to cirrhosis or liver cancer, pathology, and treatment indications and options such as interferon or nucleoside analogues. Prognosis is related to factors like age, severity of liver damage, HBeAg status, and co-infections.

1. Epidemiology of hepatitis B Prevalence in Thailand 8% Has been classified to be an intermediate endemic country for HBV infection

2. Transmission of hepatitis B Vertical transmission Sexual transmission Blood: IDU, blood transfusion Household contact

3. Viral Hepatitis B DNA virus Hepatitis B antigens Hepatitis B DNA: indicate viral load HBV DNA polymerase (DNAp): indicate disease progression Hepatitis B core protein (HBcAg): can be detected from liver Bx Hepatitis B surface protein (HBsAg): appear1-6 wks before symptom HBe protein (HbeAg): indicate actively producing virus Hepatitis B antibodies Anti-HBC: first detected Ab, appear around 8 weeks after infection HBeAb: appear a few weeks after HBeAg no longer detectable HBsAb: the last antibodies to appear, Can neutralise the virus, so provide protection against HBV. HBV morphology

4. Clinical manifestation IP 50-150 days Acute hepatitis: 10% in children. 30-40% in adult : Flu-like symptom to fulminant hepatitis Chronic hepatitis: 70-90% of infants infected at age < 1 yr 10-40% of children infected at 4-6 yrs 6-10% of children infected after age 7 yrs

5. Serological marker of acute and resolved hepatitis B Serological marker of chronic hepatitis B

6. Interpretation of hepatitis B Serology Test Result Interpretation HBsAg Negative Anti-HBc Negative Susceptible Anti-HBs Negative HBsAg Negative Anti-HBc Negative Immune due to natural infection Anti-HBs Positive HBs-Ag Positive Anti-HBc Positive Acutely infected IgM anti-HBc Positive Anti-HBs Negative HBs-Ag Positive Anti-HBc Positive Chronically infected IgM anti-HBc Negative Anti-HBs Negative HBs-Ag Negative 1.Might be recovering from acute infection Anti-HBc Positive 2.Might be distantly immune Anti-HBs Negative 3.False positive anti-HBc 4.Chronically infected with undertectable level of HBsAg

7. Natural history of chronic hepatitis B The course is highly variable, can be described by 3 phases 1.Immune tolerance phase: high level of virus in serum (HBeAg positive), minimal hepatic inflammation 2.Active phase: intermittent or continuous hepatitis of varying severity, seroconversion, anti-HBe positive may occur 3.Residual or inactive phase: low viral concentration with minimal inflammatory activity

8. Liver Pathology There is a poor correlation between symptom or level of liver enzyme and histologic features of the liver Liver Bx: Method Percutanious liver Bx Transjugular liver Bx Laparoscopic liver Bx Fine-needle aspiration Bx: accuracy 80-90%

9. Normal liver histology AHB with marked periportal bridging necrosis CHB gradeIII necroinflammation and intralobular necrosis stage IV fibrosis

10. Damage Scores for Liver Biopsy Histology Activity Index (HAI-Knodell Score ) Periportal ± Intralobular Bridging Score Degeneration Score Portal Score Fibrosis Score Necrosis and focal Inflammation Necrosis None 0 None 0 No portal 0 No 0 inflammation Fibrosis Mild Mild degeneration Mild Fibrous Piecemeal 1 and/or 1 inflammatory 1 Portal 1 Necrosis cells in ≤ 1/3 expansion hepatocellular of portal tracts necrosis in 1/3 of lobules or nodules Moderate Necrosis Moderate Moderate Bridging (involves ≥ (involvement of (increased Fibrosis 50% of the 3 of 1/3-2/3 of inflammatory 3 (portal - 3 Circumference lobules or cells in 1/3 portal or of most portal nodules) 2/3 of portal portal Tracts) tracts) central linkage)

11. Periportal ± Intralobular Bridging Score Degeneration Score Portal Score Fibrosis Score Necrosis and focal Inflammation Necrosis Marked Marked Piecemeal Marked (dense Necrosis (involvement packing of (involves ≥ 4 of ≥ 2/3 of 4 inflammatory 4 Cirrhosis 4 50% of the lobules or cells in ≥ 2/3 circumference nodules) of portal of most portal tracts) tracts) Moderate piecemeal necrosis plus 5 bridging necrosis Marked piecemeal necrosis plus 6 bridging Necrosis Multilobular 10 necrosis

12. Prognosis of chronic hepatitis From a retrospective study in China in 183 chronic hepatitis B age 31.75 ± 8.03 yrs follow up 11.8 ± 4 yrs Result : 12% develop cirrhosis, 6.5% HCC, 11% dead ( compared with 2.43% in control ) : The 5,10,15 yrs survival rate were 97.2%, 91.6% and 84.4% respectively : The 5, 10, 15 yrs incidence rate of HCC were 0,3.1%, 11.6% respectively Conclusion : old age, severe histological injury, positive HBeAg, male, alcohol abuse, co-infection with HIV, HCV and family Hx. are factors related to cirrhosis, HCC and death.

13. Treatment Indication: 1. Persistence of serum HBsAg ≥ 6 month 2. Active viral replication: HBeAg positive and/or HBV DNA > 105 copies/ml 3. Elevation of serum aminotransferase (SGPT) ≥ 2 folds for 3 months or more 4. HAI score ≥ 5 from liver biopsy Medication: 1. Alpha-interferon (IFN): 24-48 weeks: HBe-seroconversion 40-60% 2. Nucleoside analogues: Lamivudine (Zeffix), adefovir, dipivoxil, entecavir 1-5 yrs: HBe-seroconversion 10-60%