Vitamin D Receptor Activation Reduces Hepatic Inflammation via Enhancing Macrophage Autophagy in Cholestatic Mice.

Macrophage autophagy dysfunction aggravates liver injury by activating inflammasomes, which can cleave pro-IL-1ß to its active, secreted form. We investigated whether the vitamin D/vitamin D receptor (VDR) axis could up-regulate macrophage autophagy function to inhibit the activation of inflammasome-dependent IL-1ß during cholestasis. Paricalcitol (PAL; VDR agonist) was intraperitoneally injected into bile duct-ligated mice for 5 days. Up-regulation of VDR expression by PAL reduced liver injury by reducing the oxidative stress-induced inflammatory reaction in macrophages. Moreover, PAL inhibited inflammasome-dependent IL-1ß generation. Mechanistically, the knockdown of VDR increased IL-1ß generation, whereas VDR overexpression exerted the opposite effect following tert-butyl hydroperoxide treatment. The inflammasome antagonist glyburide, the caspase-1-specific inhibitor YVAD, and the reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) blocked the increase in Vdr shRNA-induced IL-1ß production. Interestingly, up-regulation of VDR also enhanced macrophage autophagy. Autophagy reduction impaired the up-regulation of VDR-inhibited macrophage inflammasome-generated IL-1ß, whereas autophagy induction showed a synergistic effect with VDR overexpression through ROS-p38 mitogen-activated protein kinase (MAPK) pathway. This result was confirmed by p38 MAPK inhibitor, MAPK activator, and ROS inhibitor NAC. Collectively, PAL triggered macrophage autophagy by suppressing activation of the ROS-p38 MAPK pathway, which, in turn, suppressed inflammasome-generated cleaved, active forms of IL-1ß, eventually leading to reduced inflammation. Thus, triggering the VDR may be a potential target for the anti-inflammatory treatment of cholestatic liver disease.

Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis.

BACKGROUND: Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. METHOD: Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. RESULTS: Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. CONCLUSION: The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Prognostic nomograms for HBV-related BCLC 0-a stage hepatocellular carcinoma incorporating aspartate aminotransferase to albumin ratio.

BACKGROUND: Curative hepatectomy is currently the first-line treatment for hepatocellular carcinoma (HCC), but the prognosis is still not optimistic. The prediction model for prognosis of hepatitis B virus (HBV)-related BCLC 0-A stage HCC has not been well established. Therefore, we aimed to develop new nomograms to predict recurrence and survival in these patients. METHODS: A total of 982 patients with HBV-related BCLC 0-A stage HCC who underwent curative hepatectomy at West China Hospital from February 2007 to February 2016 were retrospectively collected and randomly allocated to a training set and a validation set in a ratio of 4:1. Prognostic nomograms using data from the training set were developed using a Cox regression model and validated on the validation set. RESULTS: We constructed nomograms based on independent factors for recurrence-free survival (RFS) (tumor size, satellite, microvascular invasion, capsular invasion, differentiation and aspartate aminotransferase to albumin ratio (ASAR)) and overall survival (OS) (gender, tumor size, satellite, microvascular invasion, differentiation, lymphocyte count, and ASAR). Compared with conventional HCC staging systems and other nomograms reported by previous literature, our ASAR integrated nomograms predicted RFS and OS with the highest C-indexes (0.682 (95%CI: 0.646-0.709), 0.729 (95%CI: 0.691-0.766), respectively) and had well-fitted calibration curves in the training set. Concurrently, the nomograms also obtained consistent results in the validation set. DCA revealed that our nomograms provided the largest clinical net benefits. CONCLUSION: We first constructed ASAR integrated nomograms to predict the prognosis of HBV-related BCLC 0-A stage HCC patients after curative hepatectomy with good performance.

Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection.

PURPOSE: There is little information regarding the overall survival (OS) predictive ability of the combination of tumor burden score (TBS), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade for patients with hepatocellular carcinoma (HCC). Here, we aimed to develop a model including TBS, AFP, and ALBI grade to predict HCC patient OS following liver resection. METHODS: Patients (N = 1556) from six centers were randomly divided 1:1 into training and validation sets. The X-Tile software was used to determine the optimal cutoff values. The time-dependent area under the receiver operating characteristic curve (AUROC) was calculated to assess the prognostic ability of the different models. RESULTS: In the training set, tumor differentiation, TBS, AFP, ALBI grade, and Barcelona Clinic Liver Cancer (BCLC) stage were independently related to OS. According to the coefficient values of TBS, AFP, and ALBI grade, we developed the TBS-AFP-ALBI (TAA) score using a simplified point system (0, 2 for low/high TBS, 0, 1 for low/high AFP and 0,1 for ALBI grade 1/2). Patients were further divided into low TAA (TAA ≤ 1), medium TAA (TAA = 2-3), and high TAA (TAA= 4) groups. TAA scores (low: referent; medium, HR = 1.994, 95% CI = 1.492-2.666; high, HR = 2.413, 95% CI = 1.630-3.573) were independently associated with patient survival in the validation set. The TAA scores showed higher AUROCs than BCLC stage for the prediction of 1-, 3-, and 5-year OS in both the training and validation sets. CONCLUSION: TAA is a simple score that has better OS prediction performance than the BCLC stage in predicting OS for HCC patients after liver resection.

Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. METHODS: We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. RESULTS: We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. CONCLUSIONS: MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.

Brahma-Related Gene 1 Inhibition Prevents Liver Fibrosis and Cholangiocarcinoma by Attenuating Progenitor Expansion.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma-related gene 1 (Brg1), an enzymatic subunit of the switch/sucrose nonfermentable complex that is critical in stem cell maintenance and tumor promotion, is prominently up-regulated in both HPCs and iCCA; however, its role in this correlation remains undefined. APPROACH AND RESULTS: A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in patients with iCCA. In chronically injured livers induced by a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet or bile duct ligation surgery, HPCs were dramatically activated, as indicated by their enhanced expression of Brg1 and a subset of stem cell markers; however, Brg1 ablation in HPCs strongly suppressed HPC expansion and liver fibrosis. Furthermore, in a chemically induced iCCA model, inhibition of Brg1 by a specific inhibitor or inducible gene ablation markedly improved histology and suppressed iCCA growth. Mechanistically, in addition to transcriptionally promoting both Wnt receptor genes and target genes, Brg1 was found to bind to the ß-catenin/transcription factor 4 transcription complex, suggesting a possible approach for regulation of Wnt/ß-catenin signaling. CONCLUSIONS: We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and, ultimately, iCCA development in chronically injured livers, which is largely dependent on Wnt/ß-catenin signaling. Our data suggest that therapies targeting Brg1-expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.

Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Hepatic Resection Alone for Selected Patients with Moderately Advanced Multifocal Hepatocellular Carcinomas.

BACKGROUND: The role of hepatic resection (HR) combined with radiofrequency ablation (RFA) versus HR alone remains unclear for patients with multifocal hepatocellular carcinomas (HCCs). The aim of this study was to assess the outcomes of selected patients with moderately advanced multifocal HCCs after HR combined with intraoperative RFA versus HR alone. METHODS: A total of 304 selected patients with multifocal HCCs (three or fewer lesions, with the largest lesion > 4.5 cm and the residual lesion[s] ≤ 3 cm) who underwent HR plus RFA (HR+RFA group) or HR alone (HR group) were included. Propensity score matching (PSM) was used to adjust for baseline differences. Multivariable and subgroup analyses estimated the effects of clinical factors on survival. RESULTS: Both overall survival (OS) and recurrence-free survival (RFS) were comparable between both groups before and after PSM. Subgroup analysis showed that HR was associated with better RFS than HR+RFA for those patients with two tumors, or with all lesions located in the same lobe or without microvascular invasion (MVI) [all p < 0.05]. Moreover, en bloc resection provided a higher RFS than separate resection for those with all lesions in the same lobe (p = 0.039). CONCLUSION: For selected patients with moderately advanced multifocal HCCs, HR+RFA may offer similar OS and RFS as HR alone. However, HR may be more suitable for those with two tumors, or with all lesions in the same lobe or without MVI. Moreover, en bloc resection may be recommended for those with all lesions in the same lobe.

Hazard rate for postoperative recurrence in patients with hepatocellular carcinoma at Barcelona Clinic Liver Cancer stage 0 or A1: A multicenter observational study.

AIM: Surgical treatment is the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A1 hepatocellular carcinoma (HCC), and postoperative monitoring improves long-term survival. We aimed to establish a reasonable short-interval follow-up duration for patients with HCC. METHODS: The cohort for this retrospective study included 1396 HCC patients with BCLC stage 0 or A1 disease who underwent curative resection from 2013 to 2016 at five centers in China. Hazard rates for recurrence were calculated using the hazard function. RESULTS: The recurrence rates in patients with BCLC stage 0 and A1 HCC were 46.4% and 58.0%, respectively. The hazard curve for stage 0 patients was relatively flat, and the hazard rate was consistently low (peak hazard rate 0.0163). The hazard rate curve for recurrence was initially high (peak hazard rate 0.0441) in patients with BCLC stage A1 disease and showed a rapid decreasing trend within 1 year, followed by a slow decreasing trend, reaching a low level (<0.0163) at approximately 36 months. The time to low risk was 47, 41, and 51 months in patients with cirrhosis, hepatitis B virus (HBV) infection, and satellite lesions, respectively. CONCLUSIONS: A short-interval follow-up of 1 year is sufficient for HCC patients with BCLC stage 0 disease, whereas a short-interval follow-up time of 3 years should be considered for patients with stage A1 disease. The follow-up period should be appropriately prolonged for patients with cirrhosis, HBV infection, and satellite lesions.

The impact of tumor burden at the initial hepatectomy on the recurrence-to-death survival after repeat surgical resection/radiofrequency ablation: a retrospective study.

BACKGROUND: Previous studies have reported the surgical resection (SR) and radiofrequency ablation (RFA) could achieve comparable recurrence-to-death survival (RTDS). However, the impact of primary tumor burden on RTDS of patients with recurrent hepatocellular carcinoma (HCC) following SR or RFA has not been clarified. METHODS: From January 2009 to March 2015, 171 patients who underwent initial hepatectomy and second curative treatments in West China Hospital were retrospectively analyzed. Survival analysis was performed by the Kaplan-Meier method. Risk factors were identified using the Cox proportional hazard model. RESULTS: At initial hepatectomy, 96 patients (56.1%) were diagnosed with HCC within the Milan criteria (MC), and 75 patients (43.9%) were HCC beyond the MC. The clinicopathological features and re-treatment methods of recurrent HCC were similar between patients with primary HCC within or beyond the MC. Patients with primary HCC within the MC had longer recurrence time (31.4 ± 24.2 months vs. 20.2 ± 16 months, P < 0.001). The 1- and 3- year RTDS within and beyond the MC group were 88.8%, 57.6% and 79.0%, 46.3%, respectively (P = 0.093). In multivariate analysis, the recurrence time, tumor size and AFP > 400 ng/mL at the time of recurrence were associated with RTDS. CONCLUSIONS: The primary tumor burden had no impact on RTDS, but had an impact on recurrence time. The recurrence time had an impact on RTDS and might be a good index to reflect the biology of recurrent HCC.

Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study.

AIMS: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort. CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

Baseline HBV-DNA load plus AST/ALT ratio predicts prognosis of HBV-related hepatocellular carcinoma after hepatectomy: A multicentre study.

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV-related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA load and AST/ALT ratio. Based on the HBV-DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5-year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5-year OS of 42.7%. Similarly, the four types had statistically different recurrence-free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p < .001) and long-term survival (HR: 1.574, p = .001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, the classfication based on baseline HBV-DNA load and AST/ALT ratio could effectively stratify HBV-related HCC patients with distinguishable prognoses after hepatectomy.

The impact of thrombocytopenia on prognosis of HBV-related small hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: Thrombocytopenia was reported both detrimental and advantageous to hepatocellular carcinoma (HCC). However, there is little evidence showing clearly the clinical value of preoperative thrombocytopenia on the surgical outcome of patients with small HCC. This retrospective study aimed at elucidating the correlation between preoperative thrombocytopenia and surgical outcome of small HCC patients within Milan criteria treated with liver resection. METHODS: Data of hepatitis B virus (HBV)-related small HCC patients were retrospectively analyzed, and we performed the propensity score matching (PSM) analysis to overcome the imbalance of clinicopathological features. Patients enrolled were subsequently categorized into two groups according to preoperative platelet counts: thrombocytopenia group and non-thrombocytopenia group. Survival outcomes of the patients in both groups were described with the Kaplan-Meier method, and the difference was compared with a log-rank test. Cox regression analysis was applied to identify the risk factors of surgical outcome. RESULTS: After PSM, the estimated 1-, 3-, and 5-year overall survival (OS) rates for small HCC patients in the thrombocytopenia group were 94.5%, 77.0%, and 57.6%, and 95.0%, 79.6%, and 68.0%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.042). And the 1-, 3-, and 5-year estimated recurrence-free survival (RFS) rates for small HCC patients in the thrombocytopenia group were 70.4%, 51.0%, and 42.1%, and 83.8%, 63.7%, and 46.7%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.035). Multivariate analysis indicated preoperative thrombocytopenia was a significant prognosticator of poor RFS (hazard ratio (HR) = 1.388, 95% confidence interval (CI) 1.028~1.874, P = 0.033). CONCLUSION: Preoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.

Postoperative controlling nutritional status score is an independent risk factor of survival for patients with small hepatocellular carcinoma: a retrospective study.

BACKGROUND: The controlling nutritional status (CONUT) score has been widely used to evaluate the nutritional and immunological status. Clinical value of postoperative CONUT (PoCONUT) score in hepatocellular carcinoma (HCC) remains unknown. This study assessed whether PoCONUT score could serve as a useful predictor of survival for patients with small HCC. METHODS: 547 consecutive patients with small HCC who underwent liver resection between February 2007 and December 2015 were included in this retrospective case-control study. Patients were categorized into two groups: low PoCONUT group (PoCONUT score ≤ 2, n = 382) and high PoCONUT group (PoCONUT score ≥ 3, n = 165). Propensity score matching (PSM) analysis was applied to balance the bias in baseline characteristics. A cumulative survival curve was established by the Kaplan-Meier method, and differences in OS and RFS among CONUT score groups were determined by the log rank test. Cox proportional hazard regression analysis was used to evaluate the association of PoCONUT score and overall survival (OS) and recurrence-free survival (RFS), with calculation of hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). RESULTS: Cox proportional hazard regression analysis suggested that the PoCONUT score was an independent risk factor for both OS and RFS in patients with small HCC before and after PSM. CONCLUSIONS: High PoCONUT score helps to predict worse OS and RFS in patients with small HCC who underwent liver resection.

An Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus Scoring System as an Aid to Decision Making on Hepatectomy for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: A Multicenter Study.

Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α-fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH-PVTT score differentiated two groups of patients (≤/>3 points) with distinct long-term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time-dependent receiver operating characteristic curves (AUCs; 0.680-0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.

Laparoscopically anatomical versus non-anatomical liver resection for large hepatocellular carcinoma.

BACKGROUND: The role of laparoscopically anatomical resection (LAR) for hepatocellular carcinoma (HCC) remains unclear due to the more demanding technique required in laparoscopy. This study is to analyze the clinical impact of LAR compared to laparoscopically non-anatomical resection (LNAR) for HCC. METHODS: All patients received laparoscopic hepatectomy for HCC (diameter 5-10 cm) from January 2015 to December 2018 were retrospectively enrolled in this study. Patients were divided into LAR and LNAR groups. The perioperative and oncological outcomes were evaluated based on propensity score matching (PSM) method. RESULTS: After PSM, 51 patients in each group were enrolled. The operative time in LAR group was longer (240 vs 195.0 min, p = 0.012) and blood loss was more (200.0 vs 150.0 mL, p = 0.030) than those of LNAR group, respectively. The total complication rates were comparable between them (21.6% vs 17.6%, p = 0.500). The 3-year overall survival rates were 59.4% in LAR group and 38.7% in LNAR group, respectively (p = 0.045). The 3-year disease-free survival rates were 52.3% in LAR group and 27.0% in LNAR group, respectively (p = 0.042). CONCLUSION: LAR could be feasibly performed with comparable perioperative outcomes and contributed to improve long-term survival in patients with HCC (diameter 5-10 cm) when compared to LNAR.

An Eastern Hepatobiliary Surgery Hospital Microvascular Invasion Scoring System in Predicting Prognosis of Patients with Hepatocellular Carcinoma and Microvascular Invasion After R0 Liver Resection: A Large-Scale, Multicenter Study.

BACKGROUND: Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems. MATERIALS AND METHODS: Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH-MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log-rank test, and the EHBH-MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts. RESULTS: There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α-fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long-term prognoses outcomes (median OS, 55.8 vs. 19.6 months; p < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC. CONCLUSION: The EHBH-MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems. IMPLICATIONS FOR PRACTICE: Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH-MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.

Outcomes of pure laparoscopic Glissonian pedicle approach hepatectomy for hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: Few studies had been performed to concern the outcomes of pure laparoscopic Glissonian pedicle approach hepatectomy (LGAH) for hepatocellular carcinoma (HCC). The aim of this study was to compare the outcomes of LGAH versus open Glissonian pedicle approach hepatectomy (OGAH) for HCC, especially in patients with cirrhosis. METHODS: Hepatocellular carcinoma patients who underwent pure LGAH and OGAH between January 2015 and July 2017 in our institution were retrospectively enrolled in this study. Propensity score matching (PSM) of patients in a ratio of 1:1 was conducted to adjust the known confounders. The perioperative and oncological outcomes were compared between the two groups after PSM. RESULTS: Some 80 patients underwent pure LGAH and 134 had OGAH. After PSM, 67 patients in each group were well matched for analysis. Both the postoperative overall complication rates (13.4% vs. 29.9%, P = 0.021) and mean comprehensive complication index (2.63 vs. 7.40, P = 0.035) were significantly lower in the LGAH group than those in OGAH group. Although the operative time was longer in the LRH group (P < 0.001), the length of postoperative hospital stay was shorter in the LRH group (P = 0.024). Furthermore, both the 3-year overall survival rate (73.3% for LGAH vs. 77.8% for OGAH, P = 0.338) and 3-year disease-free survival rate (56.4% for LGAH vs. 62.5% for OGAH, P = 0.455) were not significantly different between the groups. CONCLUSION: Pure laparoscopic Glissonian approach may be a better alternative to open Glissonian approach in selected HCC patients, which provided fewer complications, shorter postoperative hospital stay and comparable oncological outcomes.

Successful use of the left portal vein as graft for middle hepatic vein reconstruction in left hemihepatectomy: preliminary experience on six cases.

BACKGROUND: The purpose of this research was to assess the feasibility of reconstructing the middle hepatic vein (MHV) with resected left portal vein during left hemihepatectomy. METHODS: From January 2014 to January 2018, six patients received left hemihepatectomy combined with MHV reconstruction using the resected left portal vein in West China Hospital. We reviewed the clinical data including patient details, surgical technique, graft patency, and operative results. RESULTS: All six patients underwent left hemihepatectomy for liver tumors located at left hepatocaval confluence. In these patients, MHV was resected due to tumor invading and reconstructed using the resected left portal vein as graft. The mean operating time was 316 min. Two patients developed complications: one experienced bile leakage and one experienced pleural effusion. No patient developed vascular graft complications. All the grafts remained unobstructed, and no local tumor recurrence occurred during the observation period of 13-41 months. CONCLUSIONS: Our results indicated that the left portal vein was a safe graft for hepatic vein reconstruction. In addition, left hemihepatectomy combined with middle hepatic vein resection and reconstruction using the left portal vein can be performed safely to treat liver tumors located at hepatocaval confluence.

Novel techniques and preliminary results of ex vivo liver resection and autotransplantation for end-stage hepatic alveolar echinococcosis: A study of 31 cases.

Ex vivo liver resection combined with autotransplantation is a recently introduced approach to cure end-stage hepatic alveolar echinococcosis (HAE), which is considered unresectable by conventional radical resection due to echinococcal dissemination into the crucial intrahepatic conduits and adjacent structures. This article aims discuss the manipulation details and propose reasonable indications for this promising technique. All patients successfully underwent liver autotransplantation with no intraoperative mortality. The median weight of the autografts was 636 g (360-1300 g), the median operation time was 12.5 hours (9.4-19.5 hours), and the median anhepatic phase was 309 minutes (180- 460 minutes). Intraoperative blood loss averaged 1800 mL (1200-6000 mL). Postoperative complications occurred in 13 patients during hospitalization; 5 patients experienced postoperative complications classified as Clavien-Dindo grade III or higher, and 2 patients died of intraabdominal bleeding and acute cerebral hemorrhage, respectively. Twenty-nine patients were followed for a median of 14.0 months (3-42 months), and no HAE recurrence was detected. The technique requires neither an organ donor nor any postoperative immunosuppressant, and the success of the treatment relies on meticulous preoperative assessments and precise surgical manipulation.