Purpose The immunoinhibitory receptor, programmed death 1 (PD-1), plays a critical role in immune suppression during chronic viral infection. The significance of circulating soluble PD-1 (sPD-1) in patients with chronic hepatitis B who have discontinued long-term nucleos(t)ide analog (NA) treatment remains unknown. Patients and Methods A prospective cohort study was conducted using serial blood samples from chronic hepatitis B patients who discontinued long-term NA treatment. The current analysis included 115 non-cirrhotic patients with HBV DNA negative and HBsAg positive at the moment of NA discontinuation. Levels of sPD-1 were measured in all available samples using sandwich enzyme-linked immunoassay. Results Sixty-two patients experienced a clinical relapse and 14 occurred HBsAg loss, with 8-year cumulative rates of 56.6% and 23.4%, respectively. Time-dependent receiver operating characteristic curve analysis for sPD-1 derived 156 pg/mL, which is equivalent to the detectable threshold, as an optimal cut-off value for predicting 8-year clinical relapse. Patients with detectable sPD-1 at end of treatment (EOT) had a significant lower incidence of clinical relapse (48% vs 67%, hazard ratio [HR] 0.454, p = 0.006), but a remarkable higher probability of HBsAg loss (33.7% vs 2.4%, HR 9.17, p = 0.038), compared to those who with undetectable sPD-1, respectively. Conclusion EOT sPD-1 levels predicted clinical relapse and HBsAg loss after treatment discontinuation and may help to guide a finite NA treatment plan for patients with chronic hepatitis B virus infection.
Objective: The objective of this study was to evaluate the characteristics of high body mass index (BMI) and normal weight people living with HIV after antiretroviral therapy (ART) and establish a model. Methods: A total of 290 people living with HIV after 1 year of ART treatment were enrolled and divided into two groups based on whether their BMI index was <24 or ⩾24 at week 48. The demographic, clinical data were collected and analyzed. Multivariable logistic regression analysis was performed. A model was established and use to predict the occurrence of certain diseases. Results: A total of 290 people living with HIV were included in this study; 200 had a normal BMI (BMI < 24) and 90 were high BMI (BMI ⩾ 24) after 1-year ART. Their baseline characteristics were significantly different in relation to age ( p = 0.007), sex distribution ( p = 0.040), ART regimen ( p = 0.040), alanine aminotransferase levels ( p < 0.001), and three major serum lipid levels: triglycerides ( p < 0.001), cholesterol ( p = 0.011), and low-density lipoprotein ( p = 0.005). A multivariate logistic regression analysis resulted in the development of a model for the diagnosis of high BMI and hyperlipidemia. The model score is an independent risk factor for hyperlipidemia (odds ratio = 2.674, p = 0.001) and high BMI ( p < 0.001). The model score is significantly correlated with the controlled attenuation parameter (CAP) value ( r = 0.230, p < 0.001) and can be used to divide the severity of liver steatosis based on CAP value. Conclusions: This study demonstrated a easy-to-use model to detect high BMI, hyperlipidemia, and liver steatosis in people living with HIV without risk factors for BMI changing at baseline after 1 year of ART treatment.
Context: When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment. Objectives: This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels. Methods: A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models. Results: In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels > 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively. Conclusions: The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.
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