Tenofovir versus lamivudine followed by tenofovir in severe exacerbation of hepatitis B: a randomized controlled study

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) had the advantages of low price, quick onset, good efficacy and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM/TDF groups died or received liver transplantation (P=0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24 and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE.

Development and Validation of a Novel Risk Prediction Model Using Recursive Feature Elimination Algorithm for Acute-on-Chronic Liver Failure in Chronic Hepatitis B Patients With Severe Acute Exacerbation

Background: Patients with chronic hepatitis B (CHB) with severe acute exacerbation (SAE) are at a progression stage of acute-on-chronic liver failure (ACLF) but uniform models for predicting ACLF occurrence are lacking. We aimed to present a risk prediction model to early identify the patients at a high risk of ACLF and predict the survival of the patient.Methods: We selected the best variable combination using a novel recursive feature elimination algorithm to develop and validate a classification regression model and also an online application on a cloud server from the training cohort with a total of 342 patients with CHB with SAE and two external cohorts with a sample size of 96 and 65 patients, respectively.Findings: An excellent prediction model called the PATA model including four predictors, prothrombin time (PT), age, total bilirubin (Tbil), and alanine aminotransferase (ALT) could achieve an area under the receiver operating characteristic curve (AUC) of 0.959 (95% CI 0.941–0.977) in the development set, and AUC of 0.932 (95% CI 0.876–0.987) and 0.905 (95% CI 0.826–0.984) in the two external validation cohorts, respectively. The calibration curve for risk prediction probability of ACLF showed optimal agreement between prediction by PATA model and actual observation. After predictive stratification into different risk groups, the C-index of predictive 90-days mortality was 0.720 (0.675–0.765) for the PATA model, 0.549 (0.506–0.592) for the end-stage liver disease score model, and 0.648 (0.581–0.715) for Child–Turcotte–Pugh scoring system.Interpretation: The highlypredictive risk model and easy-to-use online application can accurately predict the risk of ACLF with a poor prognosis. They may facilitate risk communication and guidetherapeutic options.

Cessation of Nucleos(t)ide Analogue Therapy in Non-Cirrhotic Hepatitis B Patients with Prior Severe Acute Exacerbation

Chronic hepatitis B (CHB) with severe acute exacerbation (SAE) is an urgent problem requiring nucleos(t)ide analogue (NA) therapy. We aim to evaluate the clinical relapse (CR) risk after discontinuing NA in patients with prior SAE. Methods: In this retrospective cohort study, CHB patients who discontinued NA therapy were screened between October, 2003 and January, 2019. A total of 78 non-cirrhotic patients who had received NA therapy for CHB with SAE, i.e., bilirubin ≥ 2 mg/dL and/or prothrombin time prolongation ≥3 s, (SAE group) were matched 1:2 with 156 controls without SAE (non-SAE group) by means of propensity scores (age, gender, NA categories, NA therapy duration, and HBeAg status). Results: The 5-year cumulative incidences of severe CR, i.e., ALT > 10X ULN, (42.78%, 95%CI: 27.84–57.73% vs. 25.42%, 95%CI: 16.26–34.58%; p = 0.045) and SAE recurrence (25.91%, 95%CI: 10.91–40.91% vs. 1.04%, 95%CI: 0–3.07%; p < 0.001) were significantly higher in the SAE group. Prior SAE history (HR 1.79, 95%CI: 1.04–3.06) was an independent factor for severe CR. The 5-year cumulative incidence of HBsAg seroclearance was significantly higher in the SAE group than that in the non-SAE group (16.82%, 95%CI: 2.34–31.30% vs. 6.02%, 95%CI: 0–13.23%; p = 0.049). Conclusions: Even though it creates a greater chance of HBsAg seroclearance, NA therapy cessation may result in a high risk of severe CR in non-cirrhotic CHB patients with prior SAE.

Peak-Inspiratory-Flow-Rate Guided Inhalation Therapy Reduce Severe Exacerbation of COPD

Optimal peak inspiratory flow rate (PIFR) is crucial for inhalation therapy in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the impact of PIFR-guided inhalation therapy on the clinical outcomes among patients with varying severities of COPD. A PIFR-guided inhalation therapy, including PIFR assessment and PIFR-guided inhaler education, was introduced in a pay-for-performance COPD management program in National Taiwan University Hospital. Among 383 COPD patients, there was significant reduction in incidence of severe acute exacerbation in the PIFR-guided inhalation therapy (PIFR group) than conventional inhaler education (control group) (11.9 vs. 21.1%, p = 0.019) during one-year follow-up. A multivariable Cox’s proportional-hazards analysis revealed that the PIFR-guided inhalation therapy was a significant, independent factor associated with the reduced risk of severe exacerbation (adjusted hazard ratio = 0.49, 95% confidence interval, 0.28–0.84, p = 0.011). Subgroup analysis found PIFR-guided inhalation therapy was more beneficial to patients with older age, short body stature, COPD stage 1&amp;2, group C&amp;D (frequent exacerbation phenotype), and using multiple inhalers. This study showed the PIFR-guided inhalation therapy significantly reduced the incidence of severe acute exacerbation than conventional inhaler education in patients with COPD. Careful PIFR-assessment and education would be crucial in the management of COPD.

Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU

Background To assess the ability of procalcitonin (PCT) to distinguish between bacterial and nonbacterial causes of patients with severe acute exacerbation of COPD (AECOPD) admitted to the ICU, we conducted a retrospective analysis of two prospective studies including 375 patients with severe AECOPD with suspected lower respiratory tract infections. PCT levels were sequentially assessed at the time of inclusion, 6 h after and at day 1, using a sensitive immunoassay. The patients were classified according to the presence of a documented bacterial infection (including bacterial and viral coinfection) (BAC + group), or the absence of a documented bacterial infection (i.e., a documented viral infection alone or absence of a documented pathogen) (BAC- group). The accuracy of PCT levels in predicting bacterial infection (BAC + group) vs no bacterial infection (BAC- group) at different time points was evaluated by receiver operating characteristic (ROC) analysis. Results Regarding the entire cohort (n = 375), at any time, the PCT levels significantly differed between groups (Kruskal–Wallis test, p < 0.001). A pairwise comparison showed that PCT levels were significantly higher in patients with bacterial infection (n = 94) than in patients without documented pathogens (n = 218) (p < 0.001). No significant difference was observed between patients with bacterial and viral infection (n = 63). For example, the median PCT-H0 levels were 0.64 ng/ml [0.22–0.87] in the bacterial group vs 0.24 ng/ml [0.15–0.37] in the viral group and 0.16 ng/mL [0.11–0.22] in the group without documented pathogens. With a c-index of 0.64 (95% CI; 0.58–0.71) at H0, 0.64 [95% CI 0.57–0.70] at H6 and 0.63 (95% CI; 0.56–0.69) at H24, PCT had a low accuracy for predicting bacterial infection (BAC + group). Conclusion Despite higher PCT levels in severe AECOPD caused by bacterial infection, PCT had a poor accuracy to distinguish between bacterial and nonbacterial infection. Procalcitonin might not be sufficient as a standalone marker for initiating antibiotic treatment in this setting.