Subject(s)
Epilepsy , Nodding Syndrome , Onchocerciasis , Epilepsy/complications , Epilepsy/epidemiology , Humans , Nodding Syndrome/complications , Nodding Syndrome/diagnosis , Nodding Syndrome/epidemiology , Onchocerciasis/complications , Onchocerciasis/diagnosis , Onchocerciasis/epidemiology , PhenotypeABSTRACT
BACKGROUND: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. AIM: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. METHODS: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. RESULTS: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. CONCLUSION: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B e Antigens/immunology , Hepatitis B, Chronic/drug therapy , Nucleosides/therapeutic use , Adult , Antibodies, Viral/blood , Cohort Studies , Female , Hepatitis B virus/immunology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/immunology , Humans , Male , Middle Aged , Recurrence , Seroconversion , Treatment Outcome , Withholding TreatmentABSTRACT
The relevance of the use of DNA adduct frequencies as a parameter for the extent of mutation induction by monofunctional alkylating agents was investigated in cultured Chinese hamster cells and in rat skin fibroblasts treated in vivo with the test chemicals. The nature of the biologically significant DNA adducts was investigated by DNA sequence analysis of mutations induced at the hypoxanthine-guanine phophoribosyltransferase (hprt) gene. The results show that under conditions where O6-alkylguanine is a persistent DNA lesion more than 50% of the mutations are GC to AT transitions indicating that the frequency of O6-alkylguanine is a good parameter for mutation induction. However, in target cells which are able to remove alkyl groups from the O6 position of guanine, alkylating agents with a low nucleophilic selectivity (e.g. N-ethyl-N-nitrosourea (ENU) and N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)) exert most of their mutagenic activity most likely via the induction of O2-ethylthymine.
