Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the Grey Zone.

BACKGROUND: Grey Zone (GZ) is an ill-defined situation including patients falling between inactive carrier (IC) state and HBeAg-negative chronic hepatitis B (HBeAg-negative CHB). AIMS: To assess the long-term outcomes of GZ patients compared to IC in the absence of treatment. METHODS: Retrospective analysis of 287 IC and GZ HBeAg-negative patients. Patients were classified into 4 groups at baseline: HBV-DNA <2000 IU/mL and ALT <40 U/L (IC), HBV-DNA <2000 IU/mL and ALT 40-80 U/L (GZ-1), HBV-DNA 2000-20 000 IU/mL and ALT <40 U/L (GZ-2) or ALT 40-80 U/L (GZ-3). Data were also analysed using AASLD ALT criteria. RESULTS: After a median follow-up of 8.2 (5-19) years, HBsAg loss occurred in about 15% ICs or GZ patients. Transition into IC state occurred in 40% of GZ patients. DNA fluctuations >2000 IU/mL correlated inversely with transition into IC and HBsAg loss. HBsAg levels were significantly lower in ICs than in GZ patients (338 IU/mL [20-3269] vs 5763 IU/mL [2172-17 754]; P < 0.05). Among the latter group, there was an increasing gradient of HBsAg levels from GZ-1 to GZ-3 patients (P < 0.05). HBeAg-negative CHB occurred in only 18 (6.3%) GZ patients. No patient developed cirrhosis nor advanced fibrosis. ALT/HBV-DNA fluctuations and HBeAg-negative CHB development were more frequent in genotype B/C patients, whereas HBsAg loss occurred only in genotype A/D patients. CONCLUSIONS: Most Caucasian GZ patients present excellent long-term outcomes in the absence of treatment, with a high rate of HBsAg loss and low rate of progression to HBeAg-negative CHB. HBV-genotyping and HBsAg levels could help to predict outcomes and better classify GZ patients.

Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with an interferon-free regimen.

BACKGROUND: A few cases of hepatitis B virus (HBV) reactivation during anti-viral therapy against hepatitis C (HCV) have been reported. However, the information regarding the real impact of this phenomenon is scarce. AIM: To evaluate the risk of HBV reactivation during anti-viral therapy against HCV with an interferon-free regimen with direct-acting anti-virals (DAAs). METHODS: Observational and prospective study of 352 patients receiving DAAs therapy between September 2015 and May 2016. HBV-DNA and ALT levels were monitored at baseline, at week 4 of anti-viral therapy, at end of treatment and 12 weeks after treatment discontinuation in patients with HBV surface antigen (HBsAg) positive or HBV core antibody (anti-HBc) positive before starting anti-viral therapy. RESULTS: Ten (2.8%) and 64 (18%) patients were HBsAg and anti-HBc positive at baseline, respectively. Five (50%) of 10 HBsAg positive and one (1.6%) of 64 anti-HBc positive patients presented HBV virological reactivation (>1log increase in HBV-DNA levels). None of these patients presented clinical reactivation (increase in ALT levels). CONCLUSIONS: HBV virological reactivation is frequent in HBsAg+ patients receiving anti-viral therapy against HCV. However, HBV-DNA elevations were modest (<20 000 IU/mL) and without clinical impact (no ALT elevation).