Patients treated with long-term combined entecavir and tenofovir for chronic hepatitis B had overall and liver-related 8-year survival rates similar to the general population, except for those with hepatocellular carcinoma, according to recently published data.
“The use of current first-line nucleos(t)ide analogues (NAs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF), has offered prolonged inhibition of HBV replication in almost all compliant [chronic HBV (CHB)] patients, improvement of liver necroinflammation and fibrosis, sometimes reversion of histological cirrhosis and prevention or even reversal of early liver decompensation,” George V. Papatheodoridis, MD, PhD, from the Laiko General Hospital, Greece, and colleagues wrote.
To evaluate the survival outcomes and effects of long-term treatment with ETV and TDF, Papatheodoridis and colleagues enrolled 1,951 adult, Caucasian patients with CHB, 526 of whom had compensated cirrhosis.
During a median follow-up of 6 years (range, 1-14 years), 84 patients died of any cause. The 8-year overall cumulative probabilities were 99.7% at 1 year, 97.8% at 3 years, 95.9% at 5 years and 94.1% at 8 years.
Multivariate analysis showed that older age per year (HR = 1.04; 95% CI, 1.02-1.06), HCC development (HR = 35.95; 95% CI, 21.14-61.11) and lower platelet levels per 104/mm3 (HR = 0.96; 95% CI, 0.91-1) correlated independently with higher risk for mortality.
Thirty-four patients died of liver disease. The overall cumulative probabilities were 99.9% at 1 year, 99.4% at 3 years, 98.3% at 5 years and 97.4% at 8 years. Multivariate analysis showed that development of HCC correlated independently with a higher risk for liver-related mortality (HR = 139.2; 95% CI, 48.59-398.79).
One hundred-eighteen patients developed HCC. After a median of 19.2 months of follow-up, three patients with HCC died due to causes unrelated to liver disease, 29 died due to HCC and 15 underwent liver transplantation. The overall mortality rate was 5.88 (95% CI, 3.85-7.7) deaths per 100 patients with HCC per year.
The researchers matched the study cohort by age, sex, country and calendar year with the general population to compare mortality rates. The overall standardized mortality ratio (SMR) was 0.82 (95% CI, 0.66-1.03), 0.78 for men (95% CI, 0.63-1.59) and 1 for women (95% CI, 0.41-0.82).
Compared with the general population, the SMR was lower in patients without cirrhosis (0.58; 95% CI, 0.41-0.82), similar in patients with cirrhosis (1.22; 95% CI, 0.9-1.66), lower in patients who did not develop HCC regardless of baseline cirrhosis (0.58; 95% CI, 0.44-0.77), and higher in patients who developed HCC (3.09; 95% CI, 2.13-4.48).
“Given that the existing CHB patients, particularly those who remain undiagnosed are becoming older and perhaps are progressing to more advanced stages of liver disease, the incidence and mortality of HBV related HCC are expected to increase in the near future,” the researchers wrote. “Thus, effective screening programs should be implemented in order to diagnose and treat the existing CHB patients at younger ages and earlier stages. Since HCC may also develop in effectively treated patients, careful evaluation of the patients’ HCC risk and HCC surveillance are mandatory.” – by Talitha Bennett
Disclosure: The authors report no relevant financial disclosures.