Bulevirtide monotherapy prevents liver decompensation and reduces mortality in patients with HDV-related cirrhosis: a case control study with propensity score weighted analysis

Background and aim Bulevirtide (BLV) monotherapy yields high rates of virological and biochemical response in hepatitis Delta (HDV) cirrhotic patients, however clinical benefits on hard outcomes remain unknown. Methods Patients with HDV-related cirrhosis treated with BLV monotherapy in a retrospective multicenter European study (SAVE-D) were compared with untreated HDV cirrhotic patients enrolled in a previous cohort study (Romeo, Gastroenterology 2009). Liver-related events (LRE: HCC, decompensation) and overall mortality were compared by inverse probability treatment weighting (IPTW) analysis. Results The BLV-treated cohort included 176 patients (median follow-up: 15 [2-46] months): at BLV start, median age was 50 (19-82) years, 59% men, ALT 77 (23-1,074) U/L, albumin 3.9 (2.8-4.9) g/dL, 100% CPT score A, 55% with varices. The untreated cohort included 140 patients (median follow-up: 91 [3-359] months): at study entry, median age was 40 (18-66) years, 78% men, ALT 102 (11-3,054) U/L, albumin 4.0 (2.0-5.2) g/dL, 94% CPT score A, 46% with varices. Overall, the 2-year cumulative probabilities of LRE were 6.9% (95% CI 3-11%) in the BLV-treated cohort vs. 15.7% (95% CI 9-22%) in untreated patients (p=0.02): 4.9% vs. 6.7% for de-novo HCC (p=0.45) and 2.0% vs. 9.1% for decompensation (p=0.01), respectively. The 2-year probability of overall mortality was 1.2% (95% CI 0.3-3%) vs. 3% (95% CI 0.5-6%) in BLV-treated vs. untreated patients (p=0.13). By IPTW analysis adjusted for confounding baseline factors and competing mortality risks, the BLV-treated cohort had a significantly decreased risk of all-type liver-related events (HR 0.38; 95% CI 0.24-0.60, p<0.0001), decompensation (HR 0.15; 95% CI 0.06-0.36, p<0.0001) and mortality (HR 0.27; 95% CI 0.08-0.93, p=0.04) compared to untreated patients. Conversely, the HCC risk was similar (HR 0.76; 95% CI 0.42-1.40, p=0.38). Conclusions In HDV cirrhotic patients, a 2-year course of BLV monotherapy resulted in lower risks of decompensation and mortality, but did not impact HCC risk.