Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term ...HBsAg seroclearance after entecavir cessation.
This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance.
A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p <0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p <0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed.
The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption.
Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy.
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•Predictors of HBsAg seroclearance following finite nucleos(t)ide analogue (NA) therapy have important clinical implications.•The ALT/qHBsAg ratio may reflect the balance between host control and virological activity after NA withdrawal.•The ALT/qHBsAg ratio from end-of-treatment up to week 48 predicted HBsAg seroclearance after stopping entecavir.•The ALT/qHBsAg ratio had excellent diagnostic performance for predicting HBsAg seroclearance.•The predictive performance of the ALT/qHBsAg ratio remained consistent, regardless of whether entecavir was resumed.
Sources of heterogeneity in risk of stroke and mortality risk following acute-stroke in schizophrenia are understudied. We systematically searched four electronic-databases until 1-November-2022, and ...conducted meta-analysis to synthesize estimates of stroke-risk and post-stroke mortality for schizophrenia patients relative to non-schizophrenia counterparts. Subgroup-analyses and meta-regression models stratified by sex, nature of sample (incident/prevalent), geographical region, study-period and time-frame following stroke were conducted when applicable. Fifteen and 5 studies were included for meta-analysis of stroke-risk (n=18,368,253; 129,095 schizophrenia patients) and all-cause post-stroke mortality (n=289,231; 4,477 schizophrenia patients), respectively. Schizophrenia patients exhibited elevated stroke-risk (relative-risk =1.5595% CI:1.31-1.84) relative to non-schizophrenia controls. Schizophrenia was associated with increased stroke-risk in both sexes, study-periods of 1990s and 2000s, and irrespective of nature of sample and geographical regions. Meta-regression revealed regional differences in relative-risk for stroke, but limited by small number of studies. After removal of an outlier study, meta-analysis demonstrated that schizophrenia was associated with increased overall (hazard-ratio=1.371.30-1.44), short-term (≤90 days; 1.291.14-1.46) and longer-term (≥1 year; 1.451.32-1.60) post-stroke mortality rates. Raised post-stroke mortality rate for schizophrenia was observed irrespective of nature of sample, geographical regions and study-periods. Taken together, schizophrenia is associated with increased stroke-risk and post-stroke mortality. Multilevel-interventions are required to reduce these physical-health disparities.
