Plasma pituitary adenylate cyclase activating polypeptide (PACAP) levels in chronic hepatitis B patients under lamivudine treatment

OBJECTIVE: Lamivudine is a nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Plasma pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide that is produced within the lymphoid microenvironment and induces the production of Th2-type cytokines. The aim of our study was to investigate the possible alterations of plasma PACAP-38 levels in chronic hepatitis B (CHB) patients during lamivudine treatment and to compare them with biochemical, virological and histological data. METHODS: Plasma PACAP-38 levels were measured using competitive radio-immune analysis (RIA) in 25 CHB patients before and after completion of a 52-week lamivudine treatment period and in 22 healthy blood donors. Biochemical evaluation was done at baseline and every three months during treatment. Virological evaluation (HBV-DNA) was performed at baseline and at weeks 24 and 52 of treatment. Baseline liver histology was assessed for all patients at the beginning and at week 52 of the study for histological comparison with the pretreatment biopsy, according to the Ishak scoring system. Statistical evaluation of data was done using analysis of variance and Student's t-test. RESULTS: Virological breakthrough was observed in seven (28%) patients at week 52 of treatment. Histological improvement was observed in 21 (84%) CHB patients, despite the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutations. Plasma PACAP-38 levels were significantly lower in CHB patients at baseline than in healthy blood donors. Significant elevation of plasma peptide levels was observed in CHB patients after the completion of lamivudine treatment period, even in the subgroup of those who exhibited YMDD variants. CONCLUSION: The elevation of plasma PACAP-38 levels in treated CHB patients following lamivudine-induced elimination of viraemia suggests a possible alteration of T-cellular immune response, resulting in biochemical and histological remission of liver disease, even in patients who exhibited virological breakthrough.