Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease 35 g/L, international normalised ratio <1.50 and total bilirubin <34 μmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.
Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined. This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120. At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p = 0.002). A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation. Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase.
Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.
To investigate the clinical value of FibroScan transient elastography for assessing portal hypertension in liver cirrhosis patients by determining the relationship between the liver or spleen stiffness measurement with the imaging parameters of esophageal varices, portal vein width, spleen volume, and splenic vein width. A total of 259 patients with liver cirrhosis underwent FibroScan measurement, ultrasound, computed tomography and routine blood analyses. One-hundred-and-one of those patients also underwent endoscopy to diagnose esophageal varices. Receiver operating characteristic (ROC) curves were generated and the areas under the curves (AUCs) were calculated to assess the accuracy of the FibroScan liver and spleen stiffness measurements to predict esophageal varices. Pearson's correlation analysis was used to assess the relationship between clinical features. The median liver and spleen stiffness of the cirrhotic patients were 24.27 kPa and 44.64 kPa, respectively. Liver and spleen stiffness increased in conjunction with increases in Child-Pugh score. Liver stiffness was positively correlated with spleen stiffness (P less than 0.05). Liver and spleen stiffness were positively correlated with esophageal varices, portal vein width, spleen thickness, spleen volume, and splenic vein width. The correlation of spleen stiffness was higher than that of liver stiffness. Spleen stiffness was also negatively correlated with white blood cell count and platelet count. Liver and spleen stiffness also increased in conjunction with increased severity of esophageal varices. The AUC of spleen stiffness was higher than that of liver stiffness for predicting esophageal varices (0.804 vs. 0.737). The optimal cut-off level of spleen stiffness was 44.5 kPa (sensitivity: 88%; specificity: 68%). The estimated prevalence of esophageal varices was 97.87% and the optimized cut-off level of liver stiffness was 18.0 kPa. FibroScan appears to be a clinically valuable non-invasive method to assess portal hypertension in cirrhotic patients. Both liver and spleen stiffness measurements correlated with portal hypertension but the spleen stiffness measurement may be of higher clinical value.
Objective: Although pegylated interferon α-2b (PEG-IFN α-2b) therapy for chronic hepatitis B has received increasing attention, determining the optimal treatment course remains challenging. This research aimed to develop an efficient model for predicting interferon (IFN) treatment course.Methods: Patients with chronic hepatitis B, undergoing PEG-IFN α-2b monotherapy or combined with NAs (Nucleoside Analogs), were recruited from January 2018 to December 2023 at Tianjin Third Central Hospital. All patients achieved hepatitis B surface antigen (HBsAg) clearance post-treatment.Result: The study enrolled 176 patients with chronic hepatitis B, with the median IFN treatment course of 35.23 ± 25.22 weeks. They were randomly divided into two cohorts in a ratio of 7:3. And there were 123 patients in the training cohort and 53 patients in the validation cohort. Univariable and multivariable analyses demonstrated that baseline HBsAg, 12 weeks HBsAg and the presence of cirrhosis significantly influenced IFN treatment course, and both are risk factors (β=7.27,4.27,10.91; p<0.05). After adjusting for confounding factors, HBsAg remained a significant predictor (β=6.99, 95%CI: 3.59,10.40; p<0.05), which was finally included to establish the model. The actual and predicted values in the validation cohort were highly matched, meanwhile the mean absolute percentage error (MAPE), root mean square error (RMSE) and accuracy (ACC) of the validation cohort were calculated. External validation also suggests that the model can be used as a tool for initial assessment.Conclusion: Baseline HBsAg in chronic hepatitis B patients were a risk factor for prolonged IFN treatment course with a positive correlation. Ultimately, a personalized model based on baseline HBsAg levels can be established to roughly estimate the duration of interferon therapy prior to treatment initiation, thereby guiding clinical decision-making.
To investigate the diagnostic utility of a noninvasive method based on spleen volume for the accurate diagnosis of severe portal hypertension (PH). We enrolled 260 patients undergoing hepatic venous pressure gradient (HVPG) assessment and enhanced CT at Tianjin Third Central Hospital (December 2019-July 2023), with clinical data collected. Patients were stratified by HVPG levels: ≥16 mmHg (severe PH group) and < 16 mmHg (non-severe PH group). We included 120 cirrhotic patients who met the inclusion criteria. Splenic volume exhibited a linear correlation with HVPG (r = 0.364, p < 0.001). Univariate and multivariate logistic regression analyses identified spleen volume, age, and serum albumin as independent risk factors for severe PH (p < 0.05). Accordingly, a clinical diagnostic model was developed, named the "S-HVPG" score. The area under the curve (AUC) for the "S-HVPG" score was 0.803, with an optimal threshold of 0.694, achieving sensitivity, specificity, positive predictive value(PPV), and negative predictive value (NPV) of 78.8%, 74.3%, 88.2%, and 59.1%, respectively. The spleen volume-based "S-HVPG" scoring system introduces a novel, straightforward, noninvasive approach for diagnosing severe PH. A cutoff value of 0.694 for the S-HVPG score effectively distinguishes patients with severe PH from those with cirrhosis.