PPAR agonists are often used in HBV infected patients with metabolic disorders. However, as liver-enriched transcriptional factors, PPARs would activate HBV replication. Risks exsit in such patients. This study aimed to assess the influence of commonly used synthetic PPAR agonists on hepatitis B virus (HBV) transcription, replication and expression through HBV replicative mouse models, providing information for physicians to make necessary monitoring and therapeutic adjustment when HBV infected patients receive PPAR agonists treatment. The HBV replicative mouse model was established by hydrodynamic injection of HBV replicative plasmid and the mice were divided into four groups and treated daily for 3 days with saline, PPAR pan-agonist (bezafibrate), PPARα agonist (fenofibrate) and PPARγ agonist (rosiglitazone) respectively. Their serum samples were collected for ECLIA analysis of HBsAg and HBeAg and real-time PCR analysis of Serum HBV DNA. The liver samples were collected for DNA (Southern) filter hybridization of HBV replication intermediates, real-time PCR analysis of HBV mRNA and immunohistochemistry (IHC) analysis of hepatic HBcAg. The alternation of viral transcription, replication and expression were compared in these groups. Serum HBsAg, HBeAg and HBV DNA were significantly elevated after PPAR agonist treatment. So did the viral replication intermediates in mouse livers. HBV mRNA was also significantly increased by these PPAR agonists, implying that PPAR agonists activate HBV replication at transcription level. Moreover, hepatic HBcAg expression in mouse livers with PPAR agonist treatment was elevated as well. Our in vivo study proved that synthetic PPAR agonists bezafibrate, fenofibrate and rosiglitazone would increase HBV replication. It suggested that when HBV infected patients were treated with PPARs agonists because of metabolic diseases, HBV viral load should be monitored and regimens may need to be adjusted, an antiviral therapy may be added.

An insight into the molecular characteristics of hepatitis C virus for clinicians

The suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy.

The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3–804.4). Adjusted RCS models showed linear exposure–response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40–3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42–3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF.

The impact of lactate-to-albumin ratio (LAR) on mortality of critically ill cirrhotic patients with sepsis is scant. Critically ill cirrhotic patients with sepsis were obtained from the MIMIC-IV database (v3.0). Cox regression models alone and in combination with restricted cubic splines, generalized additive models and smoothed curve fitting were used to investigate the relationship between LAR and all-cause mortality. A total of 1864 patients were included. The 30-day, 90-day, and 180-day all-cause mortality rates were 38.0%, 46.3%, and 49.5%, respectively. Higher LAR were significantly and nonlinearly associated with higher risks of 30-day, 90-day, and 180-day all-cause mortality (all adjusted HR = 1.17, P < 0.001). L-shaped associations between LAR and 30-day, 90-day, and 180-day all-cause mortality were observed, with an inflection point of 1.05 (P for log-likelihood ratio < 0.01). Compared with patients with LAR < 1.05, patients with LAR ≥ 1.05 had higher risks of 30-day, 90-day, and 180-day all-cause mortality (adjusted HR (95% CI): 1.48 (1.27–1.72), 1.44 (1.25–1.66), and 1.38 (1.21–1.57), respectively). No potential modifiers were found in the relationship between LAR and mortality. LAR was positively and nonlinearly associated with all-cause mortality in critically ill cirrhotic patients with sepsis. Thus, it could be used as a prognostic biomarker.

Background: Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail.Methods: A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality.Results: A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15–8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34–10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52–35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69–1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73–0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3–5 sessions of ALSS treatment was lower than that of patients received 1–2 sessions (aHR (95% CI), 0.34 (0.20–0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3–5 sessions (0.69 (0.43–1.11), p = 0.128).Conclusion: ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3–5 sessions of ALSS treatment might be reasonable.