Lamivudine for patients with chronic hepatitis B and advanced liver disease
N = 651
- Population
- Patients with chronic hepatitis B and histologically confirmed cirrhosis or advanced fibrosis; 98% Asian and 85% male.
- Design
- Randomised, placebo-controlled trial. Patients with chronic hepatitis B and histologically confirmed cirrhosis or advanced fibrosis were randomly assigned 2:1 to lamivudine 100 mg per day or placebo for a maximum of five years. An independent data and safety monitoring board performed interim analyses; the study was terminated after a median duration of treatment of 32.4 months (range 0 to 42) because of a significant difference in the number of end points reached.
- Primary endpoint
- Disease progression in chronic hepatitis B
- Arms
- Lamivudine (experimental, n = 436): Lamivudine 100 mg per day for up to five years
- Placebo (control, n = 215): Placebo for up to five years
- People
- Liaw YF
Disease progression in chronic hepatitis BHR 0.45Δ Disease progression in chronic hepatitis B−9.9 pointsIncidence of hepatocellular carcinomaHR 0.49Δ Incidence of hepatocellular carcinoma−3.5 points
Show the numbers
| Endpoint | Analysis | Lamivudine | Placebo | Effect |
|---|---|---|---|---|
| Disease progression in chronic hepatitis BRandomised patients as described in the abstract (analysis population not stated)Primary end point as defined in the trial: time to disease progression, a composite of hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices or death related to liver disease. The arm percentages are the shares of patients who reached an end point. | primaryLiaw 2004 | 7.8% | 17.7% | HR 0.45P=0.001Child-Pugh score increased in 3.4% on lamivudine and 8.8% on placebo (hazard ratio 0.45, P=0.02). Genotypic resistance (YMDD) mutations developed in 49% of lamivudine-treated patients. Serious adverse events: 12% on lamivudine, 18% on placebo. |
| Incidence of hepatocellular carcinomaRandomised patients as described in the abstract (analysis population not stated)Hepatocellular carcinoma as one component of the composite primary end point, reported separately in the abstract. | exploratoryLiaw 2004 | 3.9% | 7.4% | HR 0.49P=0.047Not a separate primary end point (HCC is one component of the composite primary end point, so the analysis is labelled exploratory); the abstract gives no confidence interval. |
| Endpoint | Analysis | Lamivudine | Placebo | Effect |
|---|---|---|---|---|
| Disease progression in chronic hepatitis BRandomised patients as described in the abstract (analysis population not stated)Primary end point as defined in the trial: time to disease progression, a composite of hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices or death related to liver disease. The arm percentages are the shares of patients who reached an end point. | primaryLiaw 2004 | 7.8% | 17.7% | HR 0.45P=0.001Child-Pugh score increased in 3.4% on lamivudine and 8.8% on placebo (hazard ratio 0.45, P=0.02). Genotypic resistance (YMDD) mutations developed in 49% of lamivudine-treated patients. Serious adverse events: 12% on lamivudine, 18% on placebo. |
| Incidence of hepatocellular carcinomaRandomised patients as described in the abstract (analysis population not stated)Hepatocellular carcinoma as one component of the composite primary end point, reported separately in the abstract. | exploratoryLiaw 2004 | 3.9% | 7.4% | HR 0.49P=0.047Not a separate primary end point (HCC is one component of the composite primary end point, so the analysis is labelled exploratory); the abstract gives no confidence interval. |