• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/pathology
• Hepatitis B, Chronic/complications
• Elasticity Imaging Techniques/methods
• Platelet Count
• Practice Guidelines as Topic
• World Health Organization
• Aspartate Aminotransferases/blood
• Severity of Illness Index
• Biopsy

• 001 World Health Organization

• Humans
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Hepatitis B virus/genetics
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Antigens, Surface
• DNA, Viral
• Inflammation

• Liver cirrhosis
• cancer
• hepatitis B virus
• hepatocellular carcinoma
• non-invasive fibrosis marker
• prognosis

• hepatic tumor
• model
• platelet
• prognosis
• recurrence

Hepatic alveolar echinococcosis (HAE) and liver cancer had similarities in imaging results, clinical characteristics, and so on. And it is difficult for clinicians to distinguish them before operation. The aim of our study was to build a differential diagnosis nomogram based on platelet (PLT) score model and use internal validation to check the model. The predicting model was constructed by the retrospective database that included in 153 patients with HAE (66 cases) or liver cancer (87 cases), and all cases was confirmed by clinicopathology and collected from November 2011 to December 2018. Lasso regression analysis model was used to construct data dimensionality reduction, elements selection, and building prediction model based on the 9 PLT-based scores. A multi-factor regression analysis was performed to construct a simplified prediction model, and we added the selected PLT-based scores and relevant clinicopathologic features into the nomogram. Identification capability, calibration, and clinical serviceability of the simplified model were evaluated by the Harrell’s concordance index (C-index), calibration plot, receiver operating characteristic curve (ROC), and decision curve. An internal validation was also evaluated by the bootstrap resampling. The simplified model, including in 4 selected factors, was significantly associated with differential diagnosis of HAE and liver cancer. Predictors of the simplified diagnosis nomogram consisted of the API index, the FIB-4 index, fibro-quotent (FibroQ), and fibrosis index constructed by King’s College Hospital (King’s score). The model presented a perfect identification capability, with a high C-index of 0.929 (0.919 through internal validation), and good calibration. The area under the curve (AUC) values of this simplified prediction nomogram was 0.929, and the result of ROC indicated that this nomogram had a good predictive value. Decision curve analysis showed that our differential diagnosis nomogram had clinically identification capability. In conclusion, the differential diagnosis nomogram could be feasibly performed to verify the preoperative individualized diagnosis of HAE and liver cancer.

• ALBI grade
• hepatocellular carcinoma
• transarterial chemoembolization (TACE)

The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok’s index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok’s index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.

Several noninvasive models based on routine laboratory index have been developed to predict liver fibrosis. Our aim is to discuss whether these indexes could predict prognosis in patients with hepatocellular carcinoma undergoing hepatectomy.

This study retrospectively enrolled 788 consecutive hepatocellular carcinoma patients undergoing liver resection in the cohort. Univariate and multivariate analysis were used to identify the risk factors of complications, survival, and disease-free survival.

Fibrosis-4 index had the best prediction ability for cirrhosis among other noninvasive models. Both the univariate and multivariate analyses showed that fibrosis-4 was independent risk factor for survival and disease-free survival. With the optimal cutoff value of 3.15, patients with fibrosis-4 ⩾3.15 had higher postoperative hepatic insufficiency (P=0.006) and worse survival than the fibrosis-4<3.15 group. The corresponding 1-year, 3-year, and 5-year overall survival were 80.9%, 56.3%, and 44.6% in the High fibrosis-4 group and were 86.5%, 69.9%, and 63.2% in the Low fibrosis-4 group, respectively (P<0.001). Worse disease-free survival was also observed in the fibrosis-4 ⩾3.15 group; the corresponding 1-year, 3-year, and 5-year disease-free survival were 74.9%, 45.3%, and 24.6% for the fibrosis-4 ⩾3.15 group and were 81.8%, 54.9%, and 34.4% for the fibrosis-4<3.15 group (P=0.009).

Fibrosis-4 is useful for assessing the short-term and long-term results for hepatocellular carcinoma patients with liver resection.

Nucleos(t)ide analogues (NUCs) treatment can reduce the risk of hepatocellular carcinoma (HCC) development and recurrence in chronic hepatitis B (CHB) patients. However, the risk of recurrence in CHB patients who develop HCC despite NUC treatment remains unclear.

167 consecutive CHB patients receiving curative resection for HCC with NUC therapy after surgery were retrospectively enrolled. Thirty-eight patients who developed HCC despite NUC therapy for more than 1 year were defined as secondary prevention failure. The other 129 patients started NUC therapy after surgery. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated.

The 5-year RFS and OS rates were 44.7% and 77.3%, respectively. Sex, BMI, BCLC stage, AFP levels and cirrhosis status were the independent predictors of RFS, while microvascular invasion was the independent predictor of OS. The RFS was comparable between patients with and without NUC secondary prevention. In the subgroup analysis, the RFS was significantly worse in cirrhotic patients with secondary prevention failure (hazard ratio = 2.373, p = 0.009). Secondary prevention failure did not have adverse impact on OS. Among 84 patients with recurrence, 58.3% of the cases remained in BCLC stage A, and 53.6% received a second curative treatment. Long-term NUC therapy may lead to a decline of non-invasive indices of hepatic fibrosis in HCC patients.

In general, the risk of recurrence and survival are comparable between patients with and without secondary prevention failure. However, a higher risk of recurrence was observed in cirrhotic patients with secondary prevention failure.

• Aged
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/complications
• Female
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/physiopathology
• Humans
• Liver Neoplasms/complications
• Male
• Middle Aged
• Recurrence
• Risk Factors
• Survival Analysis

• Ministry of Science and Technology, Taiwan (TW)
• Taipei Veterans General Hospital

To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB).

We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients.

The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.

The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.

• Gamma-glutamyltraspeptidase-to-platelet ratio
• APRI
• FIB-4
• Chronic hepatitis B
• Hepatic fibrosis

• Adult
• Biomarkers/blood
• Biopsy
• Feasibility Studies
• Female
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/pathology
• Humans
• Liver/pathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Liver Function Tests
• Male
• Middle Aged
• Platelet Count
• ROC Curve
• Retrospective Studies
• Severity of Illness Index
• gamma-Glutamyltransferase/blood

• blood biomarkers
• chronic hepatitis B virus infection
• diagnosis
• liver fibrosis

• FIB-4
• Fibroscan
• cirrhosis
• enhanced liver fibrosis (ELF)
• fibrotest

To compare the performance of several simple, noninvasive models comprising various serum markers in diagnosing significant liver fibrosis in the same sample of patients with chronic hepatitis B (CHB) with the same judgment standard.

A total of 308 patients with CHB who had undergone liver biopsy, laboratory tests, and liver stiffness measurement (LSM) at the Southwest Hospital, Chongqing, China between March 2010 and April 2014 were retrospectively studied. Receiver operating characteristic (ROC) curves and area under ROC curves (AUROCs) were used to analyze the results of the models, which incorporated age-platelet (PLT) index (API model), aspartate transaminase (AST) to alanine aminotransferase (ALT) ratio (AAR model), AST to PLT ratio index (APRI model), γ-glutamyl transpeptidase (GGT) to PLT ratio index (GPRI model), GGT-PLT-albumin index (S index model), age-AST-PLT-ALT index (FIB-4 model), and age-AST-PLT-ALT-international normalized ratio index (Fibro-Q model).

The AUROCs of the S index, GPRI, FIB-4, APRI, API, Fibro-Q, AAR, and LSM for predicting significant liver fibrosis were 0.726 (P < 0.001), 0.726 (P < 0.001), 0.621 (P = 0.001), 0.619 (P = 0.001), 0.580 (P = 0.033), 0.569 (P = 0.066), 0.495 (P = 0.886), and 0.757 (P < 0.001), respectively. The S index and GPRI had the highest correlation with histopathological scores (r = 0.373, P < 0.001; r = 0.372, P < 0.001, respectively) and LSM values (r = 0.516, P < 0.001; r = 0.513, P < 0.001, respectively). When LSM was combined with S index and GPRI, the AUROCs were 0.753 (P < 0.001) and 0.746 (P < 0.001), respectively.

S index and GPRI had the best diagnostic performance for significant liver fibrosis and were robust predictors of significant liver fibrosis in patients with CHB for whom transient elastography was unavailable.

AIM: To explore the effects of platelet count (PLT) and 11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma (HCC).

METHODS: We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy. Preoperative data, including laboratory biochemical results, were used to calculate the 11 indices included in the analysis. We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence. Cumulative rates of HCC recurrence were calculated using Kaplan-Meier survival curves and differences were analyzed by log-rank tests. Multivariate analyses were performed to identify independent predictors of recurrence, early recurrence (within one year after surgery), and late recurrence in HCC. To obtain better prognostic models, PLT-based indices were analyzed separately after being expressed as binary and continuous variables. Two platelet-unrelated, validated HCC prognostic models were included in the analyses as reference indices. Additional analyses were performed after patients were stratified based on hepatitis B virus infection status, cirrhosis, and tumor size to investigate the significance of platelets in different subgroups.

RESULTS: In the study cohort, 44.2% (76/172) of patients experienced HCC recurrence, and 50.6% (87/172) died during a median follow-up time of 46 mo. PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence (P < 0.05). Multivariate analysis indicated that, among the clinical parameters, presence of ascites, PLT ≥ 148 × 10⁹/L, alkaline phosphatase ≥ 116 U/L, and tumor size ≥ 5 cm were independently associated with a higher risk of HCC recurrence (P < 0.05). Independent and significant models included the aspartate aminotransferase/PLT index, fibrosis index based on the four factors, fibro-quotient, aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index, and the PLT/age/alkaline phosphatase/alpha-fetoprotein/aspartate aminotransferase index. There were different risk factors between early and late recurrences, and PLT and these indices were more inclined to influence late recurrence. PLT was only predictive of recurrence in non-cirrhotic HCC patients, and was not influenced by tumor size, which was a critical confounder in our study.

CONCLUSION: PLT and PLT-based noninvasive models are effective tools for predicting postoperative recurrence, especially late recurrence. Larger cohorts are needed to validate our findings.

• Alkaline phosphatase
• Alpha-fetoprotein
• Aspartate aminotransferase
• Blood platelets
• Hepatocellular carcinoma
• Recurrence

• Adult
• Area Under Curve
• Ascites/blood
• Ascites/pathology
• Biomarkers, Tumor/blood
• Blood Platelets
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Chi-Square Distribution
• Decision Support Techniques
• Female
• Hepatectomy/adverse effects
• Hepatectomy/mortality
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/blood
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Models, Biological
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Platelet Count
• Predictive Value of Tests
• Proportional Hazards Models
• ROC Curve
• Retrospective Studies
• Risk Factors
• Time Factors
• Treatment Outcome
• Tumor Burden

• Liver cirrhosis
• alkaline phosphatase
• blood platelets
• gamma-glutamyltransferase
• hepatectomy
• hepatocellular carcinoma
• survival

• Adult
• Biomarkers/blood
• Ceruloplasmin/metabolism
• Female
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Humans
• Liver Cirrhosis/blood
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/virology
• Male
• Middle Aged
• Multivariate Analysis
• ROC Curve
• Retrospective Studies

• Alanine aminotransferase
• aspartate aminotransferase
• chronic hepatitis B
• liver fibrosis
• platelet count

AIM: To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.

METHODS: We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals. Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis. A new fibrosis index [globulin/platelet (GP) model] was developed, including globulin (GLOB) and platelet count (PLT). GP model = GLOB (g/mL) × 100/PLT (× 10⁹/L). We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.

RESULTS: Thirteen clinical biochemical and hematological variables [sex, age, PLT, alanine aminotransferase, aspartate aminotransferase (AST), albumin, GLOB, total bilirubin (T.bil), direct bilirubin (D.bil), glutamyltransferase, alkaline phosphatase, HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1, F2-F3 and F4). Bivariate Spearman’s rank correlation analysis showed that six variables, including age, PLT, T.bil, D.bil, GLOB and PT, were correlated with the three fibrosis stages (FS). Correlation coefficients were 0.23, -0.412, 0.208, 0.220, 0.314 and 0.212; and P value was 0.014, < 0.001, 0.026, 0.018, 0.001 and 0.024, respectively. Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT: F = 11.772, P < 0.001; GLOB: F = 6.612, P = 0.002). Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R² = 0.237). By Spearman’s rank correlation analysis, GP model was significantly correlated with the three FS (r = 0.466, P < 0.001). The median values in F0-F1, F2-F3 and F4 were 1.461, 1.720 and 2.634. Compared with the six available models (fibrosis index, AST-platelet ratio, FIB-4, fibrosis-cirrhosis index and age-AST model and age-PLT ratio), GP model showed a highest correlation coefficient. The sensitivity and positive predictive value at a cutoff value < 1.68 for predicting minimal fibrosis F0-F1 were 72.4% and 71.2%, respectively. The specificity and negative predictive value at a cutoff value < 2.53 for the prediction of cirrhosis were 84.5% and 96.7%. The area under the curve (AUC) of GP model for predicting minimal fibrosis and cirrhosis was 0.762 [95% confidence interval (CI): 0.676-0.848] and 0.781 (95% CI: 0.638-0.924). Although the differences were not statistically significant between GP model and the other models (P all > 0.05), the AUC of GP model was the largest among the seven models.

CONCLUSION: By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.

• Globulin
• Platelet
• Globulin/platelet model
• Liver fibrosis
• Noninvasive fibrosis biomarker
• Chronic hepatitis B virus