Abstract:
TITLE: Changes of serum HBsAg levels in HBeAg-negative chronic hepatitis B patients treated with tenofovir
AUTHORS (FIRST NAME, LAST NAME): George V. Papatheodoridis1, Christos K. Triantos2, Emilia Hadziyannis1, Konstantinos Zisimopoulos2, Anastasia Georgiou1, Katerina Margariti1, Melanie Deutsch1, Vasiliki Nikolopoulou1, Spilios Manolakopoulos1
INSTITUTIONS (ALL): 1. 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece.
2. Department of Gastroenterology, University Hospital of Patras, Patras, Greece.
ABSTRACT BODY: Background/Aim: Serum HBsAg represents the only serological marker of chronic HBV infection in HBeAg-negative chronic hepatitis B (CHB) patients effectively treated with nucleos(t)ide analogue(s) [NA(s)] and therefore HBsAg decline may be an important predictor of on-therapy and most importantly off-treatment remission. We studied the changes of serum HBsAg levels in a cohort of patients with HBeAg-negative compensated CHB who had been treated with tenofovir disoproxil fumarate (TDF) for at least 12 months.
Methods: Until April 2013, 137 patients (M/F: 102/35, mean age: 58±16 years) who started therapy with TDF 300mg daily between 2008 and 2011 have been included. TDF has been given for a mean of 32±15 months. Of the 137 patients, 69 were naive to NAs (Group A), while 68 had been exposed to other NAs (lamivudine resistance: 59, telbivudine resistance: 6, other: 3) (Group B). TDF was given as monotherapy in group A and in combination with lamivudine, at least during the initial period, in group B patients. Stored serum samples taken before and at 6, 12, 24 and 36 months after TDF initiation were tested for serum HBsAg levels on the Architect analyzer (Abbott Labs).
Results: Before TDF, Group A and B patients had median serum levels of ALT 78 and 49 IU/L (P<0.001), HBV DNA 5.8 and 3.3 log10 IU/mL (p<0.001) and HBsAg 3.5 and 3.2 log10 IU/mL (p=0.177), respectively. Virological remission rates (HBV DNA undetectable by PCR) were 93% at 12 months and 98% beyond 12 months, without any difference between Groups A and B. Compared to before TDF, levels of HBsAg decreased by a median of 0.06, 0.12, 030 and 0.37 log10 IU/mL at 6, 12, 24 and 36 months, respectively (p0.350 for all comparisons). No decline of HBsAg levels was observed in 24%, 18% and 16% of patients at 12, 24 and 36 months of TDF therapy. Three patients cleared HBsAg, while the cumulative rates of HBsAg levels <500 IU/mL were 17%, 27% and 43% and of HBsAg levels <100 IU/mL 11%, 17% and 17% at 12, 24 and 36 months of TDF therapy.
Conclusions: In both NA(s) naive and experienced patients with HBeAg-negative CHB, TDF therapy decreases significantly serum HBsAg levels, but the rate of HBsAg decline is slow with a median of <0.5 log10 IU/mL at 36 months. However, a proportion of such patients could achieve relatively low HBsAg levels with approximately 4/10 and 1/6 of them reaching levels <500 and <100 IU/mL, respectively.