Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis

Abstract

Summary Background Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well studied. Aim To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis. Methods We studied TDF‐treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti‐viral therapy. The primary outcome was 5‐year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT). Results A total of 1088 (291 untreated and 797 TDF‐treated) patients were included in the study. Five‐year cumulative probabilities in untreated vs TDF‐treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio [aHR] 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti‐viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death. Conclusions Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.

Construction of a 13‐microRNA‐based signature and prognostic nomogram for predicting overall survival in patients with hepatocellular carcinoma

“…Many reports have shown that treatments based on etiology are beneficial to improve HCC patients' prognosis. [30][31][32][33][34] In order to identify the prognostic value of the constructed model, we tested an internal cohort, and the results were consistent with those of the primary cohort. Furthermore, even when we divided the whole cohort into a 2:1 ratio, as for training and validation, the results were indistinguishable (data not shown).…”

Hepatocellular carcinoma and death and transplantation in chronic hepatitis B treated with entecavir or tenofovir disoproxil fumarate

“…www.nature.com/scientificreports/ Since Choi et al reported that TDF, in comparison with ETV, reduced HCC by analysing large insurance claim data and hospital cohorts 1 , subsequent studies have analysed the association between NAs and the incidence of HCC. However, they have failed to show consistent results [15][16][17][18][19][20][21][22] . Of note, a recent meta-analysis including more than 60,000 patients from 15 studies demonstrated that TDF significantly reduced the risk of HCC by 20% 23 .…”

Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

“…This is reflected by the good performance of treated derived HCC risk scores in the absence of HBV DNA including the PAGE-B-related scores [24][25][26] and CAMD score [27,28]. The current first-line NA treatment has modified the natural history of CHB by a potent effect on HBV DNA suppression and a reduced risk of disease progression in both non-cirrhotic and cirrhotic patients [11,12,29]. The majority of treated patients can achieve complete viral suppression, i.e., undetectable serum HBV DNA, on treatment [30,31].…”

“…They have high antiviral effects and a high genetic barrier to drug resistance [8,10]. Long-term entecavir and TDF treatment results in reduced incidence rate of HCC [11,12]. Yet HCC risk is significantly reduced but not eliminated even in patients who have achieved prolonged complete viral suppression, as genetic and/or epigenetic aberrations with malignant potentials may have already accumulated in the background liver along with long-standing HBV infection [13].…”