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Background: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases., Aim: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC., Methods: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index., Results: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging., Conclusion: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC., Competing Interests: Conflict-of-interest statement: The authors declare no potential financial interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To investigate and compare the analytical and clinical performance of TianLong automatic hypersensitive hepatitis B virus (HBV) DNA quantification system and Roche CAP/CTM system., Methods: Two hundred blood samples for HBV DNA testing, HBV-DNA negative samples and high-titer HBV-DNA mixture samples were collected and prepared. National standard materials for serum HBV and a worldwide HBV DNA panel were employed for performance verification. The analytical performance, such as limit of detection, limit of quantification, accuracy, precision, reproducibility, linearity, genotype coverage and cross-contamination, was determined using the TianLong automatic hypersensitive HBV DNA quantification system (TL system). Correlation and Bland-Altman plot analyses were carried out to compare the clinical performance of the TL system assay and the CAP/CTM system., Results: The detection limit of the TL system was 10 IU/mL, and its limit of quantification was 30 IU/mL. The differences between the expected and tested concentrations of the national standards were less than ± 0.4 Log 10 IU/mL, which showed high accuracy of the system. Results of the precision, reproducibility and linearity tests showed that the multiple test coefficient of variation (CV) of the same sample was less than 5% for 10 2 -10 6 IU/mL; and for 30-10 8 IU/mL, the linear correlation coefficient r 2 = 0.99. The TL system detected HBV DNA (A-H) genotypes and there was no cross-contamination during the "checkerboard" test. When compared with the CAP/CTM assay, the two assays showed 100% consistency in both negative and positive sample results (15 negative samples and 185 positive samples). No statistical differences between the two assays in the HBV DNA quantification values were observed ( P > 0.05). Correlation analysis indicated a significant correlation between the two assays, r 2 = 0.9774. The Bland-Altman plot analysis showed that 98.9% of the positive data were within the 95% acceptable range, and the maximum difference was -0.49., Conclusion: The TL system has good analytical performance, and exhibits good agreement with the CAP/CTM system in clinical performance., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

Aim: To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology., Methods: Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl 4 ) at 0.4 mL every 48 h for 42 d. 18 F-labeled NGA ([ 18 F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [ 18 F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed., Results: The liver function of the fibrosis model mice was significantly impaired by the use of CCl 4 . In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [ 18 F]FNGA was found to predominantly accumulate in liver and kidneys in both control group ( n = 21) and fibrosis group ( n = 23). The liver uptake ability (LUA), peak time (T p ), and uptake rate (LUR) of [ 18 F]FNGA between healthy liver ( n = 8) and fibrosis liver ( n = 10) were significantly different ( P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) ( P < 0.05). T p was significantly correlated with both TP and glucose (Glu) concentration ( P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration ( P < 0.01 and < 0.05, respectively)., Conclusion: [ 18 F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [ 18 F]FNGA compared to the controls., Competing Interests: Conflict-of-interest statement: All authors state that no conflicts of interest exist.

Aim: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism., Methods: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively., Results: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery., Conclusion: High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.

Aim: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB)., Methods: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested., Results: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity., Conclusion: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.

Aim: To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF)., Methods: Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 μg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34(+) cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate., Results: The peripheral neutrophil and CD34(+) cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P < 0.001) compared to that in controls. After 3 mo of follow-up observation, the survival rate in the treatment group (48.1%) was significantly higher than that in the control group (21.4%) (P = 0.0181)., Conclusion: G-CSF therapy promoted CD34(+) cell mobilization in patients with HBV-associated ACLF, and improved the liver function and the survival rate of these patients.

Aim: To analyze the correlation of treatment method with the outcome of all the hepatic metastatic melanoma (HMM) patients from our hospital., Methods: There were altogether nine cases of HMM that had been treated in the PUMCH hospital during the past 25 years, from December 1984 to February 2010. All of the cases developed hepatic metastasis from primary cutaneous melanoma. A retrospective review was performed on all the cases in order to draw informative conclusion on diagnosis and treatment in correlation with the prognosis. Clinical features including symptoms, signs, blood test results, B-ultrasound and computed tomography (CT) imaging characteristics, and pathological data were analyzed in each case individually. A simple comparison was made on case by case basis instead of performing statistical analysis since the case numbers are low and patients were much diversified in each item that has been analyzed. Literatures on this subject were reviewed in order to draw a safe conclusion and found to be supportive to our finding in a much broad scope., Results: There are six males and three females whose ages ranged 39-74 years old with an average of 58.8. Patients were either with or without symptoms at the time of diagnosis. The liver function and tumor marker exam were normal in all but one patient. The incidence of HMM does not affect liver function and was not related to virus infection status in the liver. Most of these HMM patients were also accompanied by the metastases of other locations, including lung, abdominal cavity, and cervical lymph nodes. Ultrasound examinations showed lesions ranging 2-12 cm in diameter, with no- or low-echo peripheral areola. Doppler showed blood flow appeared inside some tumors as well as in the surrounding area. CT image demonstrated low density without uniformed lesions, characterized with calcification in periphery, and enhanced in the arterial phase. Contrast phase showed heterogeneous enhancement, with a density higher than normal liver tissue, which was especially apparent at the edge. Patients were treated differently with following procedures: patients #1, #6 and #8 were operated with hepatectomy with or without removal of primary lesion, and followed by comprehensive biotherapy/chemotherapy; patient #9 received hepatectomy only; patient #2 received bacille calmette-guerin treatment only; patient #7 had Mile's surgery but no hepatectomy; and patients #3, #4 and #5 had supportive treatment without specific measurement. The patients who had resections of metastatic lesions followed by post-operative comprehensive therapy have an average survival time of 30.7 mo, which is much longer than those did not receive surgery treatment (4.6 mo). Even for the patient receiving a resection of HMM only, the post-operative survival time was 18 mo at the time we reviewed the data. This patient and the patient #6 are still alive currently and subjected to continue following up., Conclusion: Surgical operation should be first choice for HMM treatment, and together with biotherapy/chemotherapy, hepatectomy is likely to bring better prognosis.

Aim: To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection-related primary hepatocellular carcinoma (HCC) after curative therapy., Methods: We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search. The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies, respectively. Seven HCV-related studies, three HBV-related studies and three studies on HBV or HCV-related HCC were identified., Results: A total of 1224 patients were included in this analysis. The estimated odds ratios (OR) for the 1-, 2-, 3- and 5-year recurrence were 0.54 [15.4% vs 24.1%, 95% confidence interval (CI): 0.32-0.89, P = 0.02], 0.42 (36.9% vs 58.0%, 95% CI: 0.19-0.90, P = 0.03), 0.37 (47.9% vs 63.8%, 95% CI: 0.19-0.71, P = 0.003), and 0.32 (66.7% vs 74.3%, 95% CI: 0.15-0.66, P = 0.002), respectively; and the OR for the 1-, 2-, 3-, 5- and 7-year mortality were 0.23 (1.2% vs 9.1%, 95% CI: 0.07-0.71, P = 0.01), 0.31 (6.4% vs 22.1%, 95% CI: 0.12-0.79, P = 0.01), 0.43 (12.7% vs 20.8%, 95% CI: 0.21-0.89, P = 0.02), 0.42 (25.1% vs 42.0%, 95% CI: 0.27-0.66, P = 0.0002) and 0.28 (31.9% vs 52.2%, 95% CI: 0.13-0.59, P = 0.0008)., Conclusion: This meta-analysis indicates the postoperative antiviral therapy, interferon in particular, may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.