Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections.This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay.Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy.Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.

This study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study’s cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% vs . 48.1%, P = 0.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.

The present study was designed to assess the correlation between serum Golgi protein 73 (GP73) and liver pathological grading and staging in patients with chronic hepatitis B (CHB). Two hundred and fifty-three patients with chronic hepatitis B virus (HBV) infections were enrolled in the present study. All patients received a serum GP73 test, and 91 CHB patients underwent liver biopsy. GP73 expression in liver tissue was assessed by immunohistochemical analysis. The results indicated that serum GP73 levels were positively correlated with disease progression in patients with chronic HBV infection (r=0.677). There was no significant difference in serum GP73 levels between hepatitis B e antigen-positive and −negative patients (P>0.05). There were also no significant differences in serum GP73 levels among specimens with varying HBV DNA contents (P>0.05). Serum GP73 levels were positively correlated with increased liver pathological grading (r=0.737) and staging (r=0.692), and immunohistochemical analysis indicated that GP73 protein expression increased concurrently with liver pathological grading and staging. In conclusion, serum GP73 was found to be correlated with liver pathological grading and staging in patients with CHB, and may be an effective indicator for the evaluation of disease progression. However, serum GP73 levels were not associated with HBV replication.

As a noninvasive marker, serum alanine aminotransferase (ALT) has limitations, because a large proportion of patients chronically infected with hepatitis B virus (HBV) suffer from severe hepatic necroinflammation, but have normal or mildly elevated ALT. In the present study, we aimed to investigate the potential value of serum Golgi protein 73 (GP73) in predicting significant hepatic necroinflamation among chronic HBV infected patients. A cohort of 497 chronic HBV infected patients was retrospectively recruited. Liver biopsy was performed in all patients and serum GP73 levels were measured by enzyme-linked immunosorbent assay. Serum GP73 increased in parallel with the increase in hepatic necroinflammatory activity grade (r = 0.682) and the stage of liver fibrosis (r = 0.539). The positive correlation of serum GP73 with the degree of hepatic necroinflammatory activity was statistically significant, while serum GP73 with the stage of liver fibrosis was weaker than that with hepatic necroinflammation. Furthermore, serum GP73 levels were significantly greater in patients with normal or mildly elevated ALT and significant hepatic necroinflammation (≥G2) than in patients with minimal to mild hepatic necroinflammation. The sensitivity and specificity of GP73 for the diagnosis of G2 hepatic necroinflammation was 42.35% and 95.0%, respectively, at a cut-off value of 88.38 ng/mL. When the cut-off value was set at 124.76 ng/mL, the sensitivity and specificity of GP73 for the diagnosis of G3 hepatic necroinflammation was 55.56% and 97.29%, respectively. These findings indicate that GP73 holds promise as an important candidate for diagnosing significant hepatic necroinflammation.

This study aimed to assess the feasibility of GP73 as a diagnostic marker for liver inflammation and fibrosis in chronic HBV patients with normal or slightly raised ALT (<2 ULN) and to develop models based on GP73 and other biochemical parameters to improve diagnostic accuracy. Serum GP73 levels were analyzed in 220 chronic HBV patients with normal or slightly raised ALT who underwent liver biopsy. The results showed that the area under the receiver operating characteristic (ROC) curve (AUC) was 0.806 for predicting significant liver inflammation (≥G2), while it was 0.742 for predicting significant fibrosis (≥S2). These results suggest that GP73 has higher diagnostic value for liver inflammation than liver fibrosis. Combining GP73, AST and ALB, as a diagnostic model for predicting significant liver inflammation, resulted in superior diagnostic performance over GP73 alone (AUC value increased from 0.806 to 0.854, z = 2.299, P = 0.021). By applying this diagnostic model, over 80% of chronic HBV patients with normal or slightly raised ALT will be correctly identified and hence avoid delay in diagnosis and treatment. In conclusion, GP73 would be an additional serum marker for predicting liver inflammation and fibrosis in chronic HBV patients with normal or slightly raised ALT.

Ligation of splenic artery (LSA) is used for the treatment of liver cirrhosis with hypersplenism. However, hypersplenism is not significantly improved following LSA treatment in some cases, and there are few reports of retreatment of hypersplenism after LSA. We report the case of a 47-year-old man with liver cirrhosis and hypersplenism who underwent LSA treatment, but did not significantly improve. Laboratory tests revealed severe leukocytopenia and thrombocytopenia. Celiac computed tomography arteriogram and digital subtraction angiography revealed two compensatory arteries connected to the hilar splenic artery from the left gastro-epiploic artery and from the dorsal pancreatic artery. Partial splenic embolization (PSE) was performed through the compensatory arteries. As a result, the patient achieved partial splenic ischemic infarction, and white blood cell and platelet counts rose and remained in the normal range. PSE is an effective therapeutic modality for the retreatment of hypersplenism when other modalities have failed.

BACKGROUND Acute-on-chronic liver failure (ACLF) is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease. AIM To explore the independent predictors of short-term prognosis in patients with hepatitis B virus (HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF. METHODS From January 2016 to December 2019, 207 patients with HBV-related ACLF attending the 910th Hospital of Chinese People's Liberation Army were continuously included in this retrospective study. Patients were stratified based on their survival status 3 mo after diagnosis. Information was collected regarding gender and age; coagulation function in terms of prothrombin time and international normalized ratio (INR); hematological profile in terms of neutrophil-to-lymphocyte ratio (NLR) and platelet count (PLT); blood biochemistry in terms of alanine aminotransferase, aspartate aminotransferase, total bilirubin (Tbil), albumin, cholinesterase, blood urea nitrogen (BUN), creatinine, blood glucose, and sodium (Na); tumor markers including alpha-fetoprotein (AFP) and Golgi protein 73 (GP73); virological indicators including HBV-DNA, HBsAg, HBeAg, Anti-HBe, and Anti-HBc; and complications including hepatic encephalopathy, hepatorenal syndrome, spontaneous peritonitis, gastrointestinal bleeding, and pulmonary infection. RESULTS There were 157 and 50 patients in the survival and death categories, respectively. Univariate analysis revealed significant differences in age, PLT, Tbil, BUN, NLR, HBsAg, AFP, GP73, INR, stage of liver failure, classification of liver failure, and incidence of complications (pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis, and upper gastrointestinal bleeding) between the two groups ( P < 0.05). GP73 [hazard ratio (HR): 1.009, 95% confidence interval (CI): 1.005-1.013, P = 0.000], middle stage of liver failure (HR: 5.056, 95%CI: 1.792-14.269, P = 0.002), late stage of liver failure (HR: 22.335, 95%CI: 8.544-58.388, P = 0.000), pulmonary infection (HR: 2.056, 95%CI: 1.145-3.690, P = 0.016), hepatorenal syndrome (HR: 6.847, 95%CI: 1.930-24.291, P = 0.003), and HBsAg (HR: 0.690, 95%CI: 0.524-0.908, P = 0.008) were independent risk factors for short-term prognosis in patients with HBV-related ACLF. Following binary logistics regression analysis, we arrived at the following formula for predicting short-term prognosis: Logit(P) = Ln(P/1-P) = 0.013 × (GP73 ng/mL) + 1.907 × (middle stage of liver failure) + 4.146 × (late stage of liver failure) + 0.734 × (pulmonary infection) + 22.320 × (hepatorenal syndrome) - 0.529 × (HBsAg) - 5.224. The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Li...

Background and aim Patients with cirrhosis have a high prevalence of spontaneous portosystemic shunt (SPSS), but it remains controversial whether the presence of SPSS is associated with liver function and portal hypertension (PHT)-related complications. In this study, we aimed to investigate the prevalence, clinical characteristics and related factors of SPSS in cirrhotic patients. Methods Patients who were diagnosed with hepatitis B-related cirrhosis between Jan 2020 and Oct 2021 were retrospectively recruited from five centers in China. All eligible patients were classified into SPSS and non-SPSS groups and their clinical characteristics were compared. Logistic regression analyses were performed to identify clinical characteristics associated with SPSS, and then to assess the independent impact of SPSS on the risk of PHT-related complications. Results Of the 1282 patients included in this study, SPSS was identified in 488 patients (38.1%). SPSS group had a higher proportion of patients with hepatofugal flow in portal vein, thinner diameter of right branch of portal vein (RPV), thicker diameter of left branch of portal vein (LPV), splenic vein (SV) and superior mesenteric vein (SMV), more severe liver function impairment, higher incidence and severity of esophageal and gastric varices (EGV), and a higher prevalence of PHT-related complications [EGV bleeding (EGVB), portal vein thrombosis (PVT), hepatic encephalopathy (HE), ascites, and hepatocellular carcinoma (HCC)] (all P < 0.05). On multivariable logistic regression analyses, MELD score, diameter of RPV and SV, hepatofugal flow in portal vein, EV or GV or EGV on radiological evaluation, presence of EGVB, PVT, HE, and moderate–severe ascites were independently associated with SPSS (all P < 0.05). In addition, presence of SPSS was identified as an independent risk factor for EGVB, PVT and HE (all P < 0.05). Conclusion SPSS may indicate severe liver damage and a high risk of PHT-related complications.