Healthy Liver

Liver biopsy

•Percutaneous liver biopsy with or without ultrasonic guidance is a standard diagnostic approach for establishing the presence of chronic hepatitis. Laparoscopic liver biopsy, which is used in large referral centers, has the advantage of minimizing the sample error by facilitating gross inspection of the liver and thus ensuring an adequate biopsy sample size. This figure depicts a laparoscopic view of a patient with chronic active hepatitis and early cirrhosis

•Courtesy of David Bernstein and Eugene R. Schiff

Detection of serologic markers of hepatitis B virus (HBV) infection, as a function of time, in acute cases.

Lamivudine is a Potent Inhibitor of HBV Replication

•A nucleoside analogue: (-)-2’,3’-dideoxy-3’-thiacytidine

•Antiviral activity against HBV and HIV

•Inhibits viral RNA-dependent DNA polymerase

Lamivudine has an Excellent Pharmacokinetic Profile

•Optimal dose is 100 mg once daily

•Rapidly absorbed

•Minimal liver metabolism

•Excreted unchanged in the urine

•Moderate to severe renal impairment requires dose reduction

•No significant drug interactions

Patient Entry Criteria

Patients had to have evidence of:-

•CHB - HBsAg +ve for at least 6m

•HBV replication - HBeAg +ve and HBV DNA +ve at screen and for 1m prior to screen

•Liver disease - elevated ALT 1.3xULN but < 10xULN in western studies; normal or elevated ALT in the Asian study

One Year of Lamivudine - Conclusions

Virology

•Suppresses serum HBV DNA

•Leads to HBeAg seroconversion Liver disease

•Improves hepatic necro-inflammation

•Reduces progression of fibrosis

•Reduces progression to cirrhosis

•Normalises serum ALT

•Improves liver histology irrespective of baseline ALT

Resistance to Anti-Viral Drugs

Genotypic resistance – changes in the virus that disrupt interactions between the drug and its molecular target

Clinical resistance – loss of efficacy due to above changes