Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis.

Many noninvasive methods for diagnosing liver fibrosis (LF) have been proposed. To determine the best method for diagnosing LF in nonalcoholic fatty liver disease (NAFLD), we conducted a systemic review and meta-analysis to compare the performance of aspartate aminotransferase to platelets ratio index (APRI), fibrosis-4 index (FIB-4), BARD score, NAFLD fibrosis score (NFS), FibroScan, shear wave elastography (SWE), and magnetic resonance elastography (MRE) for diagnosing LF in NAFLD. We compared the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC) of these noninvasive methods for detecting significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis. Heterogeneity was explored using meta-regression. Sixty-four articles with a total of 13,046 NAFLD subjects were included. The overall mean prevalence of SF, AF, and cirrhosis was 45.0%, 24.0%, and 9.4% in NAFLD patients, respectively. With an APRI threshold of 1.0 and 1.5, the sensitivities and specificities were 50.0% and 84.0% and 18.3% and 96.1%, respectively, for AF. With a FIB-4 threshold of 2.67 and 3.25, the sensitivities and specificities were 26.6% and 96.5% and 31.8% and 96.0%, respectively, for AF. The summary sensitivities and specificities of BARD score (threshold of 2), NFS (threshold of -1.455), FibroScan M (threshold of 8.7-9), SWE, and MRE for detecting AF were 0.76 and 0.61, 0.72 and 0.70, 0.87 and 0.79, 0.90 and 0.93, and 0.84 and 0.90, respectively. The summary AUROC values using APRI, FIB-4, BARD score, NFS, FibroScan M probe, XL probe, SWE, and MRE for diagnosing AF were 0.77, 0.84, 0.76, 0.84, 0.88, 0.85, 0.95, and 0.96, respectively. CONCLUSION: MRE and SWE may have the highest diagnostic accuracy for staging fibrosis in NAFLD patients. Among the four noninvasive simple indexes, NFS and FIB-4 probably offer the best diagnostic performance for detecting AF. (Hepatology 2017;66:1486-1501).

Intraoperative endoscopic nasobiliary drainage over primary closure of the common bile duct for choledocholithiasis combined with cholecystolithiasis: a cohort study of 211 cases.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) was often used for preoperative biliary drainage in cases like cholangiocarcinoma or acute obstructive suppurative cholangitis, reports on endoscopic nasobiliary drainage (ENBD) over primary closure of the common bile duct (CBD) are limited. This study compares outcomes of laparoscopic cholecystectomy (LC) + laparoscopic CBD exploration (LCBDE) + intraoperative ENBD + primary closure of CBD with equivalent patients who underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) and subsequent LC. METHODS: From January 2013 to December 2015, 829 consecutive patients with choledocholithiasis combined with cholecystolithiasis underwent surgery in our department. 211 patients underwent LC + LCBDE + intraoperative ENBD + primary closure of CBD (group A) and 117 preoperative ERCP + subsequent LC (group B). A total of 501 patients (355 who underwent T-tube drainage and 146 who underwent transcystic exploration) were excluded from the analysis. Clinical records, operative findings, and postoperative follow-up were analyzed. RESULTS: Age and sex distribution, comorbidity, presentations, CBD diameter, and size and number of stones were similar in the two groups, and there was no postoperative mortality. Duration of surgery in group A was shorter (83 vs. 104 min, P < 0.01), as was postoperative hospital stay (6 vs. 9 days, P < 0.01). Average operative expenditure in group A was less than that of group B ($ 3816 vs. $ 4015, P < 0.01). The success rate in group A was higher (100 vs. 91%, P < 0.01). Ten patients in group B converted to LCBDE. The postoperative complication rate was higher in group B but without significant difference (1.9 vs. 4.2%, P = 0.29). Median follow-up time was 24 (3-28) months (n = 302 patients). Two patients in group B reported residual stones. CONCLUSION: LC + LCBDE + intraoperative ENBD + primary closure of CBD should have priority over preoperative ERCP + subsequent LC for choledocholithiasis combined with cholecystolithiasis.

Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta-analysis.

UNLABELLED: The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fibrosis 4 index; FIB-4) are the two most widely studied noninvasive tools for assessing liver fibrosis. Our aims were to systematically review the performance of APRI and FIB-4 in hepatitis B virus (HBV) infection in adult patients and compare their advantages and disadvantages. We examined the diagnostic accuracy of APRI and FIB-4 for significant fibrosis, advanced fibrosis, and cirrhosis based on their sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC). Heterogeneity was explored using metaregression. Our systemic review and meta-analysis included 16 articles of APRI only, 21 articles of APRI and FIB-4 and two articles of FIB-4 for detecting different levels of liver fibrosis. With an APRI threshold of 0.5, 1.0, and 1.5, the sensitivity and specificity values were 70.0% and 60.0%, 50.0% and 83.0%, and 36.9% and 92.5% for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. With an FIB-4 threshold of 1.45 and 3.25, the sensitivity and specificity values were 65.4% and 73.6% and 16.2% and 95.2% for significant fibrosis. The summary AUROC values using APRI and FIB-4 for the diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 0.7407 (95% confidence interval [CI]: 0.7033-0.7781) and 0.7844 (95% CI: 0.7450-0.8238; (Z = 1.59, P = 0.06), 0.7347 (95% CI: 0.6790-0.7904) and 0.8165 (95% CI: 0.7707-0.8623; Z = 2.01, P = 0.02), and 0.7268 (95% CI: 0.6578-0.7958) and 0.8448 (95% CI: 0.7742-0.9154; (Z = 2.34, P = 0.01), respectively. CONCLUSIONS: Our meta-analysis suggests that APRI and FIB-4 can identify hepatitis B-related fibrosis with a moderate sensitivity and accuracy.

Systematic review and meta-analysis of minimally invasive versus open approach for pancreaticoduodenectomy.

BACKGROUNDS AND OBJECTIVE: The technique of minimally invasive pancreatic surgeries has evolved rapidly, including minimally invasive pancreaticoduodenectomy (MIPD). However, controversy on safety and feasibility remains when comparing the MIPD with the open pancreaticoduodenectomy (OPD); therefore, we aimed to compare MIPD and OPD with a systemic review and meta-analysis. METHODS: Multiple electronic databases were systematically searched to identify studies (up to February 2016) comparing MIPD with OPD. Intra-operative outcomes, oncologic data, postoperative complications and postoperative recovery were evaluated. RESULTS: Twenty-two retrospective studies including 6120 patients (1018 MIPDs and 5102 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (WMD -312.00 ml, 95 % CI -436.30 to -187.70 ml, p < 0.001), transfusion rate (OR 0.41, 95 % CI 0.30-0.55, p < 0.001), wound infection (OR 0.37, 95 % CI 0.20-0.66, p < 0.001) and length of hospital stay (WMD -3.57 days, 95 % CI -5.17 to -1.98 days, p < 0.001). Meanwhile, MIPD group has a higher R0 resection rate (OR 1.47, 95 % CI 1.18-1.82, p < 0.001) and more lymph nodes harvest (WMD 1.74, 95 % CI 1.03-2.45, p < 0.001). However, it had longer operation time (WMD 83.91 min, 95 % CI 36.60-131.21 min, p < 0.001). There were no significant differences between the two procedures in morbidities (p = 0.86), postoperative pancreatic fistula (p = 0.17), delayed gastric empting (p = 0.65), vascular resection (p = 0.68), reoperation (p = 0.33) and mortality (p = 0.90). CONCLUSIONS: MIPD can be a reasonable alternative to OPD with potential advantages. However, further large-volume, well-designed RCTs with extensive follow-ups are suggested to confirm and update the findings of our analysis.

Combined Hangzhou criteria with neutrophil-lymphocyte ratio is superior to other criteria in selecting liver transplantation candidates with HBV-related hepatocellular carcinoma.

BACKGROUND: The elevation of neutrophil-lymphocyte ratio (NLR) has adverse effects on the prognosis of patients with hepatocellular carcinoma (HCC) who have received liver transplantation (LT). The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou criteria for selecting HCC patients for LT. METHODS: Receiver operating characteristic (ROC) analysis was done to determine the optimal NLR threshold. Univariate and multivariate analyses were made to evaluate the factors affecting the outcomes of HCC patients after LT. We also proposed new criteria consisting of the elevated NLR and Hangzhou criteria. ROC analysis was carried out to validate the feasibility of the new criteria. RESULTS: Three hundred and five HCC patients were included in this study. The mean follow-up time of these patients was 5.4 years. Of the 305 patients, 197 (64.6%) showed elevated NLRs (NLR > 4). The recurrence-free survival rates of the patients with elevated NLRs at 1, 3 and 5 years were lower than those of the patients with normal NLRs (NLR ≤ 4) (50.1%, 21.7% and 20.2% vs 80.5%, 58.7% and 56.4%, respectively; P < 0.001). The overall survival rate was lower in the patients with elevated NLR than in those with normal NLR at 1, 3 and 5 years (60.8%, 27.0% and 22.5% vs 78.4%, 51.1% and 47.8%, respectively; P < 0.001). Multivariate analysis demonstrated that an NLR > 4 (P = 0.034), total tumor size > 8 cm (P = 0.005), alpha-fetoprotein level > 400 µg/L (P = 0.007) and the presence of vascular invasion (P = 0.003) were independent predictors of HCC recurrence in post-transplant patients. We proposed a set of new criteria based on the elevated NLR and Hangzhou criteria. A ROC analysis demonstrated that the patients with scores ≥ 1 had an area under the curve of 0.764. CONCLUSION: The criteria combining the elevated NLR and Hangzhou criteria can be used to select patients with HCC for LT.

How to select suitable hepatocellular carcinoma for liver transplantation by preoperative neutrophil-lymphocyte ratio.

BACKGROUND/AIMS: The liver transplantation (LT) criteria for hepatocellular carcinoma (HCC) is expanding. However, most of the existing criteria are based on tumor characteristics of radiology. We aimed to build a preoperative scoring model including the neutrophil­lymphocyte ratio (NLR) to select HCC patients for LT. METHODOLOGY: Using receiver operating characteristic curve (ROC) analysis the sensitivity and specificity were highest when NLR was 3.79, so we defined NLR > 4 as elevated. By univariate and multivariate analysis, the significant predictors including NLR were used to establish a scoring model to predict outcome of HCC patients after LT. RESULTS: Of 280 HCC patients, there were 114 patients with elevated NLR. The one-, three- and five-year recurrence-free survival rates of patients with high and low NLR were 64.9%, 30.1%, 30.1% vs. 83.9%, 62.9%, 60.7% (p < 0.001). On univariate and multivariate analysis, the raised NLR (p = 0.007), total tumor size > 9 cm (p < 0.001) and vascular invasion (p < 0.001) were the significant factors in predicting outcome. By ROC analysis, the patients with a score ≥ 1 had an area under the curve (AUC) of 0.745. CONCLUSION: This scoring model including NLR can aid in selecting HCC candidates for LT.

High HBV-DNA serum levels are associated with type 2 diabetes in adults with positive HBsAg: An observational study.

Background: The prevalence of diabetes is higher in hepatitis B virus (HBV)-infected population. We aimed to examine the relationship between different serum HBV-DNA levels and type 2 diabetes in adults with positive HBV surface antigen (HBsAg). Methods: We conducted cross-sectional analyses of data obtaining from the Clinical Database System of Wuhan Union Hospital. Diabetes was defined by self-report of type 2 diabetes, fasting plasma glucose (FPG) ≥7mmol/L, or glycated hemoglobin (HbA1c) ≥6.5%. Binary logistic regression analyses were performed to investigate the factors associated with diabetes. Results: Among 12,527 HBsAg-positive adults, 2,144 (17.1%) were diabetic. Patients with serum HBV-DNA <100, 100-2000, 2000-20000 and ≥20000 IU/mL accounted for 42.2% (N=5,285), 22.6% (N=2,826), 13.3% (N=1,665) and 22.0% (N=2,751), respectively. The risk of type 2 diabetes, FPG ≥7mmol/L and HbA1c ≥6.5% in individuals with highly elevated serum HBV-DNA level (≥20000 IU/mL) were 1.38 (95% confidence interval [CI]: 1.16 to 1.65), 1.40 (95% CI: 1.16 to 1.68) and 1.78 (95% CI: 1.31 to 2.42) times relative to those with negative or lowly elevated serum HBV-DNA (<100 IU/mL). However, the analyses showed no association of moderately (2000-20000 IU/mL) to slightly (100-2000 IU/mL) raised serum HBV-DNA levels with type 2 diabetes (OR=0.88, P=0.221; OR=1.08, P=0.323), FPG ≥7mmol/L (OR=1.00, P=0.993; OR=1.11, P=0.250) and HbA1c ≥6.5% (OR=1.24, P=0.239; OR=1.17, P=0.300). Conclusion: In HBsAg-positive adults, highly elevated level rather than moderately to slightly raised levels of serum HBV-DNA is independently associated with an increased risk of type 2 diabetes.

The prevalence of depression and suicidal ideation among cancer patients in mainland China and its provinces, 1994-2021: A systematic review and meta-analysis of 201 cross-sectional studies.

To evaluate the national prevalence depression of Chinese cancer patients and clarify its potential associated factors. Twelve databases were searched from database inception through October 31, 2022 for relevant studies published in English (PubMed MEDLINE, Ovid MEDLINE, Embase, Scopus, PsycINFO, and Cochrane and Web of Science) and Chinese (China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Biomedical Literature Service System, Duxiu) that estimated point or period prevalence of depression, depressive disorder, or suicidal ideation as assessed by self-report scale or structured interview. 201 studies were eligible for inclusion in our meta-analyses. We found the national pooled prevalence rates of depression and suicidal ideation were 44.63 % (95 % CI 42.24 %-47.01 %) and 24.95 % (95 % CI 10.96 %-38.95 %), respectively. The pooled prevalence of depression was associated with study location, cancer type, comorbid chronic disease, and female sex (all P < 0.05). The distribution of the depression prevalence among cancer patients in mainland China was characterized by significant geographical variation and clustering. The highest pooled prevalence of depression was among gynecologic oncology patients. We recommend that more attention and resources be given to mental health problems such as depression and suicidal ideation among Chinese cancer patients, and that prevention programs be developed, especially in areas with a high prevalence of depression.

Prognostic Factors of Survival of Advanced Liver Cancer Patients Treated With Palliative Radiotherapy: A Retrospective Study.

AIMS: Survival benefit of liver cancer patients who undergo palliative radiotherapy varies from person to person. The present study aims to identify indicators of survival of advanced liver cancer patients receiving palliative radiotherapy. PATIENTS AND METHODS: One hundred and fifty-nine patients treated with palliative radiotherapy for advanced liver cancer were retrospectively assessed. Of the 159 patients, 103 patients were included for prediction model construction in training phase, while other 56 patients were analyzed for external validation in validation phase. In model training phase, clinical characteristics of included patients were evaluated by Kaplan-Meier curves and log-rank test. Thereafter, multivariable Cox analysis was taken to further identify characteristics with potential for prediction. In validation phase, a separate dataset including 56 patients was used for external validation. Harrell's C-index and calibration curve were used for model evaluation. Nomograms were plotted based on the model of multivariable Cox analysis. RESULTS: Thirty-one characteristics of patients were investigated in model training phase. Based on the results of Kaplan-Meier plots and log-rank tests, 6 factors were considered statistically significant. On multivariable Cox regression analysis, bone metastasis (HR = 1.781, P = 0.026), portal vein tumor thrombus (HR = 2.078, P = 0.015), alpha-fetoprotein (HR = 2.098, P = 0.007), and radiation dose (HR = 0.535, P = 0.023) show significant potential to predict the survival of advanced liver cancer patients treated with palliative radiotherapy. Moreover, nomograms predicting median overall survival, 1- and 2-year survival probability were plotted. The Harrell's C-index of the predictive model is 0.709(95%CI, 0.649-0.769) and 0.735 (95%CI, 0.666-0.804) for training model and validation model respectively. Calibration curves of the 1- and 2-year overall survival of the predictive model indicate that the predicted probabilities of OS are very close to the actual observed outcomes both in training and validation phase. CONCLUSION: Bone metastasis, portal vein tumor thrombus, alpha-fetoprotein and radiation dose are independent prognostic factors for the survival of advanced liver cancer patients treated with palliative radiotherapy.

PD-L1 regulation by SDH5 via ß-catenin/ZEB1 signaling.

Programmed death-ligand 1 (PD-L1) is a crucial target for lung cancer immunotherapy. In lung cancer patients with high PD-L1 expression, blocking or reducing its expression can inhibit tumor growth. PD-L1 is regulated by signaling pathways, transcription factors and epigenetic factors, such as the GSK3ß/ß-catenin pathway, P53 protein and EMT. In our previous study, succinate dehydrogenase 5 (SDH5) was reported to regulate ZEB1 expression, induce EMT and lead to lung cancer metastasis via the GSK3ß/ß-catenin pathway. It is possible that SDH5 is involved in the mechanisms of PD-L1 regulation.In the present study, we observed a negative correlation between the expression of PD-L1 and SDH5 in vivo and in vitro. The examination of patient tissues also confirmed our results. Furthermore, we also found that SDH5 could reverse PD-L1 expression by the GSK3ß/ß-catenin/ZEB1 pathways. All these results reveal that SDH5 regulates PD-L1 expression and suggest that SDH5 can be used as a marker to predict tumor immune micro-states and provide guidance for clinical immunotherapy.

SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response.

Radiotherapy is an effective treatment for lung cancer but lacks a reliable prediction method. Cell-free nucleic acids in plasma have been reported as a novel tumor marker. Here, we evaluate circulating succinate dehydrogenase 5 (SDH5) mRNA in plasma and SDH5 protein in tumors, assess their predictive value in lung cancer patients undergoing radiotherapy, and explore the underlying mechanisms. Methods: SDH5 expression was measured in peripheral blood samples and fresh tumor specimens from 208 non-small cell lung cancer (NSCLC) patients and correlated with clinical outcomes. SDH5 knockout mice and human xenograft mice were used to evaluate radiosensitivity. Cell growth, apoptosis, and the DNA damage response were assessed. Relevant RNA and protein levels were analyzed by qRT-PCR and Western blotting. Immunoprecipitation and GST pulldown assays were performed to detect protein-protein interactions. Polyubiquitination of p53 was examined by an in vitro ubiquitination assay. Results: Plasma and tumor SDH5 mRNA levels were positively correlated (rho=0.894, P<0.001). Patients with relatively low SDH5 levels in plasma (0.47, 0.12-0.89) and tumors (3.85, 0.96-7.23) had a better prognosis after radiotherapy (median PFS: 30.0 versus 15.0 months, hazard ratio: 0.276, 95% CI: 0.201-0.379, P<0.001). In SDH5 knockout mice, the lung epithelial cells exhibited increased DNA damage after radiation. In human lung xenograft mice, SDH5-deficient tumors had a smaller volume after radiotherapy. Furthermore, SDH5 depletion inhibits p53 degradation via the ubiquitin/proteasome pathway, which promotes apoptosis and enhances radiosensitivity in NSCLC. Conclusion: Our findings provide a novel noninvasive method for prediction of response to radiotherapy and may have significant implications for cancer radiotherapy.

Association of miR-608 rs4919510 polymorphism and cancer risk: a meta-analysis based on 13,664 subjects.

Single nucleotide polymorphisms (SNPs) in MicroRNAs (miRNAs) are involved in the mechanism of carcinogenesis. Several studies have evaluated the association of rs4919510 SNP in miR-608 with cancer susceptibility in different types of cancer, with inconclusive outcomes. To obtain a more precise estimation, we carried out this meta-analysis through systematic retrieval from the PubMed and Embase database. A total of 10 case-control studies were analyzed with 6,000 cases and 7,664 controls. The results showed that 4919510 SNP in miR-608 was significantly associated with decreased cancer risk only in recessive model (CC vs. GG+GC: OR=0.89, 95% CI: 0.82-0.97, P=0.009). By further stratified analysis, we found that rs4919510 SNP had some relationship with decreased cancer risk in both homozygote model (CC vs. GG: OR=0.59, 95% CI: 0.36-0.96, P=0.034) and dominant model (CG+ CC vs. GG: OR=0.60, 95% CI: 0.37-0.98, P=0.042) in Caucasians but no relationship in any genetic model in Asians. These results indicated that miR-608 rs4919510 polymorphism may contribute to the decreased cancer susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, to further confirm these results, well-designed large scale case-control studies are needed in the future.

Preoperatively staging liver fibrosis using noninvasive method in hepatitis B virus-infected hepatocellular carcinoma patients.

BACKGROUND: Advanced liver fibrosis can result in serious complications (even patient's death) after partial hepatectomy. Preoperatively percutaneous liver biopsy is an invasive and expensive method to assess liver fibrosis. We aim to establish a noninvasive model, on the basis of preoperative biomarkers, to predict liver fibrosis in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection. METHODS: The HBV-infected liver cancer patients who had received hepatectomy were retrospectively and prospectively enrolled in this study. Univariate analysis was used to compare the variables of the patients with mild to moderate liver fibrosis and with severe liver fibrosis. The significant factors were selected into binary logistic regression analysis. Factors determined to be significant were used to establish a noninvasive model. Then the diagnostic accuracy of this novel model was examined based on sensitivity, specificity and area under the receiver-operating characteristic curve (AUC). RESULTS: This study included 2,176 HBV-infected HCC patients who had undergone partial hepatectomy (1,682 retrospective subjects and 494 prospective subjects). Regression analysis indicated that total bilirubin and prothrombin time had positive correlation with liver fibrosis. It also demonstrated that blood platelet count and fibrinogen had negative correlation with liver fibrosis. The AUC values of the model based on these four factors for predicting significant fibrosis, advanced fibrosis and cirrhosis were 0.79-0.83, 0.83-0.85 and 0.85-0.88, respectively. CONCLUSION: The results showed that this novel preoperative model was an excellent noninvasive method for assessing liver fibrosis in HBV-infected HCC patients.

Diagnostic accuracy of APRI and FIB-4 for predicting hepatitis B virus-related liver fibrosis accompanied with hepatocellular carcinoma.

BACKGROUND: Aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis index based on four factors (FIB-4) are the two most focused non-invasive models to assess liver fibrosis. AIMS: We aimed to examine the validity of these two models for predicting hepatitis B virus (HBV)-related liver fibrosis accompanied with hepatocellular carcinoma (HCC). METHODS: We enrolled HBV-infected patients with liver cancer who had received hepatectomy. The accuracy of APRI and FIB-4 for diagnosing liver fibrosis was assessed based on their sensitivity, specificity, diagnostic efficiency, positive predictive value (PPV), negative predictive value (NPV), kappa (κ) value and area under the receiver-operating characteristic curve (AUC). RESULTS: Finally 2176 patients were included, with 1682 retrospective subjects and 494 prospective subjects. APRI (rs=0.310) and FIB-4 (rs=0.278) were positively correlated with liver fibrosis. And χ(2) analysis demonstrated that APRI and FIB-4 values correlated with different levels of liver fibrosis with all P values less than 0.01. The AUC values for APRI and FIB-4 were 0.685 and 0.626 (P=0.73) for predicting significant fibrosis, 0.681 and 0.648 (P=0.81) for differentiation of advanced fibrosis and 0.676 and 0.652 (P=0.77) for diagnosing cirrhosis. CONCLUSION: APRI and FIB-4 correlate with liver fibrosis. However these two models have low accuracy for predicting HBV-related liver fibrosis in HCC patients.

Prophylaxis against hepatitis B virus recurrence after liver transplantation: a registry study.

AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin (HBIG) in combination with different nucleos(t)ide analogues. METHODS: A total of 5333 hepatitis B surface antigen-positive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular (im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus (HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A (n = 4684): im HBIG plus lamivudine; group B (n = 491): im HBIG plus entecavir; group C (n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid (HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses. RESULTS: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B (86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P < 0.001) and C (86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P < 0.001). The 1-, 3- and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B (1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttransplant prophylactic protocol (lamivudine and HBIG vs entecavir and HBIG) were associated with HBV recurrence. CONCLUSION: Low-dose intramuscular HBIG in combination with a nucleos(t)ide analogue provides effective prophylaxis against posttransplant HBV recurrence, especially for HBIG plus entecavir.

Living donor liver transplantation does not increase tumor recurrence of hepatocellular carcinoma compared to deceased donor transplantation.

AIM: To compare the recurrence-free survival (RFS) and overall survival (OS) of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT). METHODS: We retrospectively collected clinical data from 408 liver cancer patients from February 1999 to September 2012. We used the chi-squared test or Fisher's exact test to analyze the characteristics of LDLT and DDLT. Kaplan-Meier analysis was used to compare the RFS and OS in HCC. RESULTS: Three hundred sixty HBV-positive patients (276 DDLT and 84 LDLT) were included in this study. The mean follow-up time was 27.1 mo (range 1.1-130.8 mo). One hundred eighty-five (51.2%) patients died during follow-up. The 1-, 3-, and 5-year RFS rates for LDLT were 85.2%, 55.7%, and 52.9%, respectively; for DDLT, the RFS rates were 73.2%, 49.1%, and 45.3% (P = 0.115). The OS rates were similar between the LDLT and DDLT recipients, with 1-, 3-, and 5-year survival rates of 81.8%, 49.5%, and 43.0% vs 69.5%, 43.0%, and 38.3%, respectively (P = 0.30). The outcomes of HCC according to the Milan criteria after LDLT and DDLT were not significantly different (for LDLT: 1-, 3-, and 5-year RFS: 94.7%, 78.7%, and 78.7% vs 89.2%, 77.5%, and 74.5%, P = 0.50; for DDLT: 86.1%, 68.8%, and 68.8% vs 80.5%, 62.2%, and 59.8% P = 0.53). CONCLUSION: The outcomes of LDLT for HCC are not worse compared to the outcomes of DDLT. LDLT does not increase tumor recurrence of HCC compared to DDLT.

Prognosis evaluation in patients with hepatocellular carcinoma after hepatectomy: comparison of BCLC, TNM and Hangzhou criteria staging systems.

PURPOSE: This study is to evaluate the Hangzhou criteria (HC) for patients with HCC undergoing surgical resection and to identify whether this staging system is superior to other staging systems in predicting the survival of resectable HCC. METHOD: 774 HCC patients underwent surgical resection between 2007 and 2009 in West China Hospital were enrolled retrospectively. Predictors of survival were identified using the Kaplan-Meier method and the Cox model. The disease state was staged by the HC, as well as by the TNM and BCLC staging systems. Prognostic powers were quantified using a linear trend χ2 test, c-index, and the likelihood ratio (LHR) χ2 test and correlated using Cox's regression model adjusted using the Akaike information criterion (AIC). RESULTS: Serum AFP level (P = 0.02), tumor size (P<0.001), tumor number (P<0.001), portal vein invasion (P<0.001), hepatic vein invasion (P<0.001), tumor differentiation (P<0.001), and distant organ (P = 0.016) and lymph node metastasis (P<0.001) were identified as independent risk factors of survival after resection by multivariate analysis. The comparison of the different staging system results showed that BCLC had the best homogeneity (likelihood ratio χ2 test 151.119, P<0.001), the TNM system had the best monotonicity of gradients (linear trend χ2 test 137.523, P<0.001), and discriminatory ability was the highest for the BCLC (the AUCs for 1-year mortality were 0.759) and TNM staging systems (the AUCs for 3-, and 5-year mortality were 0.738 and 0.731, respectively). However, based on the c-index and AIC, the HC was the most informative staging system in predicting survival (c-index 0.6866, AIC 5924.4729). CONCLUSIONS: The HC can provide important prognostic information after surgery. The HC were shown to be a promising survival predictor in a Chinese cohort of patients with resectable HCC.

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation.

AIM: To determine whether an elevated neutrophil-lymphocyte ratio (NLR) is negatively associated with tumor recurrence in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver transplantation (LT), and to determine the optimal predictive NLR cut-off value. METHODS: The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database. We collected data from 326 liver cancer patients who had undergone LT at our medical center. We divided the patients into groups based on their NLRs (3, 4 or 5). We then compared the clinicopathological data and long-time survival between these groups. Meanwhile, we used receiver operating characteristic analysis to determine the optimal NLR cut-off. RESULTS: Of 280 HCC patients included in this study, 263 were HBV positive. Patients with an NLR < 3 and patients with an NLR ≥ 3 but < 4 showed no significant differences in overall survival (OS) (P = 0.212) or disease-free survival (DFS) (P = 0.601). Patients with an NLR ≥ 4 but < 5 and patients with an NLR ≥ 5 also showed no significant differences in OS (P = 0.208) or DFS (P = 0.618). The 1-, 3- and 5-year OS rates of patients with an NLR < 4 vs an NLR ≥ 4 were 87.8%, 63.8% and 61.5% vs 73.9%, 36.7% and 30.3%, respectively (P < 0.001). The 1-, 3- and 5-year DFS rates of patients with an NLR < 4 vs NLR ≥ 4 were 83.9%, 62.9% and 60.7% vs 64.9%, 30.1% and 30.1%, respectively (P < 0.001). Univariate and multivariate analyses demonstrated that three factors, including NLR ≥ 4 (P = 0.002), were significant predictors of tumor recurrence in HCC patients after LT. CONCLUSION: A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma.

AIM: To explore the relationship between α-fetoprotein (AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma (HCC) thoroughly. METHODS: A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study. The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis, such as status of hepatitis B virus (HBV) infection, tumor size, tumor number, vascular invasion and degree of tumor differentiation. Also, patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP (≤ 20 µg/L, 21-400 µg/L, 401-800 µg/L, and ≥ 801 µg/L), to compare the positive rate of patient among four groups stratified by various clinicopathological variables. And the correlation of different kinds of tumor staging systems, such as TNM, Barcelona Clinic Liver Cancer (BCLC) staging classification and China staging, were compared with the serum concentration of AFP. RESULTS: A total of 2304 HCC patients were enrolled in this study totally; the mean serum level of AFP was 555.3 ± 546.6 µg/L. AFP levels were within the normal range (< 20 µg/L) in 27.4% (n = 631) of all the cases. 81.4% (n = 1875) patients were infected with HBV, and those patients had much higher serum AFP level compared with non-HBV infection ones (573.9 ± 547.7 µg/L vs 398.4 ± 522.3 µg/L, P < 0.001). The AFP level in tumors ≥ 10 cm (808.4 ± 529.2 µg/L) was significantly higher (P < 0.001) than those with tumor size 5-10 cm (499.5 ± 536.4 µg/L) and with tumor size ≤ 5 cm (444.9 ± 514.2 µg/L). AFP levels increased significantly in patients with vascular invasion (694.1 ± 546.9 µg/L vs 502.1 ± 543.1 µg/L, P < 0.001). Patients with low tumor cell differentiation (559.2 ± 545.7 µg/L) had the significantly (P = 0.007) highest AFP level compared with high differentiation (207.3 ± 420.8 µg/L) and intermediate differentiation (527.9 ± 538.4 µg/L). In the multiple variables analysis, low tumor cell differentiation [OR 6.362, 95%CI: 2.891-15.382, P = 0.006] and tumor size (≥ 10 cm) (OR 5.215, 95%CI: 1.426-13.151, P = 0.012) were independent predictors of elevated AFP concentrations (AFP > 400 µg/L). Serum AFP levels differed significantly (P < 0.001) in the D stage of BCLC (625.7 ± 529.8 µg/L) compared with stage A (506.2 ± 537.4 µg/L) and B (590.1 ± 551.1 µg/L). CONCLUSION: HCC differentiation, size and vascular invasion have strong relationships with AFP, poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP. BCLC shows better relationship with AFP.