TITLE: Viral response in long-term therapy with nucleos(t)ide analogues in chronic hepatitis B cirrhosis prevents decompensation
AUTHORS (FIRST NAME, LAST NAME): Ivana Carey1, Sarah Knighton1, Deepak Joshi1, Ashley Barnabas1, Suman Verma1, Phillip M. Harrison1, Abid Suddle1, Kosh Agarwal1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Institute of Liver Studies, Kings College School of Medicine at King's College Hospital, London, United Kingdom.
ABSTRACT BODY: Long-term therapy with nucleos(t)ide analogues (NA) in chronic hepatitis B (CHB) reduces risk of liver disease progression, improves fibrosis and prevent liver disease related complications. Viral response (VR=HBV DNA<20IU/ml) in patients with liver cirrhosis prevents complication events. Only few studies have evaluated variable aspects of long-term NA therapy in CHB cirrhosis.
Aims: To investigate the role of viral response on the improvement of synthetic function tested by MELD and UKELD scores, parameters of portal hypertension [platelets (PLT) counts, size of spleen] and preventing cirrhosis complications in patients with CHB cirrhosis during long-term NA therapy
Patients: 190 monoinfected CHB cirrhotic patients (85%histological confirmation) (median age 45y, 78%males, 43%HBeAg+) were treated in single centre with entecavir 0.5mg/day (n=78) or tenofovir 245 mg/d (n=62) or lamivudine 100mg/d +adefovir 10mg/d (n=50) for at least 2 years (median duration 5 years) and based on VR response after 1 year on therapy were divided into 2 groups: complete responders (CR) (n=130) and partial responders (PR) (n=40). Patients achieving initial CR with viral breakthrough up to levels<100IU/ml (blips) were investigated separately (n=30).
Methods: HBV DNA [log10IU/ml], haematological and biochemical markers of liver synthetic function and HCC surveillance abdominal ultrasound including size of spleen [cm] were analysed at baseline and every 6 months during therapy and MELD & UKELD scores were calculated. 32 patients had varices present at baseline.
Results: Baseline median MELD & UKELD scores were 14 and 45 and were higher in PR than CR (14 vs 12,p=0.04; 45 vs 43,p=0.04). PLT counts and size of spleen were similar between PR and CR (145 vs 159,p=0.3 & 11.7 vs 10.9,p=0.2). Baseline HBV DNA was higher in PR than CR (7.33 vs 5.27,p<0.01). Yearly virological response had 77%, 84% 90%, 96% and 98% patients; 35% patients achieved HBeAg seroconversion and 5% had HBsAg loss after 5 years NA therapy. MELD & UKELD scores improved during therapy in all patients, year 5 median MELD and UKELD scores were 12 (12 vs. 13) and 42 (42 vs 43), but PLT counts improved only in CR (year 5: 194 vs. 154,p=0.03). 18 (9%) patients developed HCC and 14 (7%) had decompensation while on therapy. HCC occurred equally in CR and PR or blips patients, but decompensation was present only in patients with PR or blips.
Conclusions: Long-term antiviral therapy with NA in CHB patients with cirrhosis improved liver synthetic function in all patients. Viral response prevented decompensation and disease progression. HCC prevalence (2%patients/year) was similar viral responders and partial responders.