Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

Tumor necrosis as a predictor of early tumor recurrence after resection in patients with hepatoma.

BACKGROUND: Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. MATERIALS AND METHODS: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. RESULTS: Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. CONCLUSION: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. METHODS: We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. RESULTS: This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). CONCLUSION: No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Tumor Necrosis Is an Indicator of Poor Prognosis Among Hepatoma Patients Undergoing Resection.

INTRODUCTION: Tumor necrosis has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients undergoing liver resection (LR). However, more evidence is needed to clarify this issue. METHODS: Patients who underwent upfront LR between 2010 and 2018 for newly diagnosed HCC without undergoing neoadjuvant therapy were enrolled in this retrospective study. Tumor necrosis was classified as present or absent according to retrospective examinations. The association between tumor necrosis, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed. RESULTS: Among 756 patients who underwent LR for HCC, tumor necrosis was present in 279 (36.9%) patients. Compared with patients without tumor necrosis, patients with tumor necrosis had higher proportions of tumors sized >5.0 cm (P < 0.001), multiple tumors (P < 0.001), microvascular or macrovascular invasion (P < 0.001), poorly differentiated or undifferentiated tumors (P < 0.001), and T stage 3 or 4 (P < 0.001) on pathological examination. The presence of tumor necrosis was associated with worse OS and RFS compared with the absence of tumor necrosis: 5-y OS was 56% versus 78% (P < 0.001); 5-y RFS was 42% versus 55% (P < 0.001). In multivariate analysis, the presence of tumor necrosis was an independent factor associated with worse OS (hazard ratio: 1.956; 95% confidence interval: 1.409-2.716; P < 0.001) and RFS (hazard ratio: 1.422; 95% confidence interval: 1.085-1.865; P = 0.011). CONCLUSIONS: Tumor necrosis was associated with worse OS and RFS among patients who underwent LR for HCC.

Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment.

Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19-14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reliable marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection.

Characteristics and prognosis of patients with large well-differentiated hepatocellular carcinoma who have undergone resection.

BACKGROUND: Large well-differentiated hepatocellular carcinoma (HCC) ≥ 3 cm (defined as atypical HCC) is uncommon. We evaluated the characteristics and outcomes of atypical HCC patients underwent liver resection (LR). METHODS: This retrospective study enrolled patients who underwent LR for HCC from 2007 to 2017. Patient characteristics and overall survival (OS) were compared between patients with atypical HCC and patients with typical HCC (moderate-to-undifferentiated HCC ≥ 3 cm). RESULTS: Among 598 patients, 51 (8.5%) had atypical HCC. Patients with atypical HCC had higher rates of non-hepatitis B or C infections (p = 0.02) and American Joint Committee on Cancer T1 pathology (p < 0.001), a lower rate of alpha-fetoprotein >20 ng/ml (p < 0.001) and a longer OS (p < 0.001) than those with typical HCC. Multivariate analysis showed that atypical HCC was associated with OS (HR = 0.50, 95% CI = 0.27-0.91, p = 0.02). CONCLUSIONS: Patients with atypical HCC have a higher rate of non-hepatitis B or C infections and a lower rate of aggressive tumor biologic behavior. Atypical HCC is an independent predictor of OS.

Clinical and novel application of FibroScan, FIB-4 and aspartate aminotransferase-to-platelet ratio index in liver fibrosis evaluation in patients with hepatocellular carcinoma and their roles in oesophageal variceal prediction.

BACKGROUND: Non-invasive techniques for liver fibrosis diagnosis are very important for clinician especially in high-risk patients for liver biopsy. We further explored the diagnostic accuracy of FibroScan, FIB-4 and aminotransferase-to-platelet ratio index (APRI) in identifying liver fibrosis and assess their predictive role for oesophageal varices in patients with hepatocellular carcinoma (HCC). METHODS: In total, 380 patients who underwent surgery for HCC were included based on retrospective study design. Liver fibrosis was pathologically diagnosed using the Ishak scoring system. Liver stiffness parameters were measured using FibroScan. APRI and FIB-4 were calculated. Among those, 121 patients who received oesophagogastroduodenoscopic examination underwent variceal evaluation. RESULTS: For liver cirrhosis diagnosis with FibroScan, the optimal cut-off values for the patients with HCC overall, left HCC and right HCC were 8.85, 11.75 and 8.70 kPa (the accuracy were 78.7%, 78.4% and 79.2%, respectively). They had high areas under the receiver operating characteristic curve of 0.84, 0.84 and 0.85. The combined FibroScan, APRI and FIB-4 had very high specificity (more than 92%) for cirrhosis diagnosis. The optimal cut-off liver stiffness values for the diagnosis of varices were all 11.2 kPa. For predicting varices, the optimal cut-off values of FIB-4 and APRI were 2.64 and 0.71, their accuracy were 64.3%-78.4%, 69.4% and 72.7%, respectively. CONCLUSIONS: FibroScan, FIB-4 and APRI have moderate accuracy for liver fibrosis diagnosis and oesophageal varices prediction in patients with hepatoma. This is a study of these non-invasive techniques applied in specific hepatoma patients and with inevitable limitations and need future more studies for validation.

Microscopic portal vein invasion is a powerful predictor of prognosis in patients with hepatocellular carcinoma who have undergone liver resection.

BACKGROUND AND OBJECTIVES: A recent study proposed simple classifications of microscopic vascular invasion (MVI): microscopic portal vein invasion (MPVI) and microvessel invasion (MI). We aim to validate these classifications of MVI. METHODS: This retrospective study consecutively enrolled 514 Barcelona Clinic Liver Cancer stage 0, A, and B naïve hepatocellular carcinoma patients who underwent liver resection in our institution from 2011 to 2017. RESULTS: Among these 514 patients, 240 patients were classified as having no MVI at all (designated as no vascular invasion, NVI), 157 patients were classified as having MI only, and 117 patients were classified as having MPVI. The 5-year overall survival (OS) rate in the MI-only group was 83.3%, which was not significantly different from that of the NVI group (87.2%), p = .20. Using NVI as a reference, multivariate analysis showed that MI-only is not an independent variable associated with OS. The 5-year OS in the MPVI group was 59.2%, which was significantly lower than those for MI-only (p < .001) and NVI groups (p < .001). Using NVI as a reference, multivariate analysis showed that MPVI is an independent variable associated with OS (HR, 3.12; 95% CI, 1.80-5.40; p < .001). CONCLUSIONS: The results of this study validate the simple MVI classifications to be clinically useful.

Elevated neutrophil-to-lymphocyte ratio and predominance of intrahepatic cholangiocarcinoma prediction of poor hepatectomy outcomes in patients with combined hepatocellular-cholangiocarcinoma.

OBJECTIVES: Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC. METHODS: We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival. RESULTS: Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival. CONCLUSIONS: Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.

FDG-PET predicted unfavorable tumor histology in living donor liver transplant recipients; a retrospective cohort study.

BACKGROUND: Tumor histology affects outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC). This study explores the association between F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and tumor histology in living donor liver transplantation (LDLT) recipients and their outcome. MATERIALS AND METHODS: Two hundred fifty-eight patients with primary liver tumors who underwent FDG-PET before LDLT were enrolled in this retrospective study. Unfavorable tumor histology was defined as primary liver tumor other than a well- or moderately differentiated HCC. Thirteen patients had unfavorable tumor histology, including 2 poorly differentiated HCC, 2 sarcomatoid HCC, 5 combined hepatocellular cholangiocarcinoma, 3 intrahepatic cholangiocarcinoma, and 1 hilar cholangiocarcinoma. RESULTS: FDG-PET positivity was significantly associated with unfavorable tumor histology (P < 0.001). Both FDG-PET positivity and unfavorable tumor histology were significant independent predictors of tumor recurrence and overall survival. In a subgroup analysis of patients with FDG-PET-positive tumors, unfavorable tumor histology was a significant independent predictor of tumor recurrence and overall survival. High FDG uptake (tumor to non-tumor uptake ratio ≥ 2) was a significant predictor of unfavorable tumor histology. Patients with high FDG uptake and/or unfavorable tumors had significantly higher 3-year cumulative recurrence rate (70.8% versus 26.2%, P = 0.004) and worse 3-year overall survival (34.1% versus 70.8%, P = 0.012) compared to those with low FDG uptake favorable tumors. CONCLUSIONS: The expression of FDG-PET is highly associated with histology of explanted HCC and predicts the recurrence. FDG-PET-positive tumors with high FDG uptake may be considered contraindication for LDLT due to high recurrence rate except when pathology proves favorable histology.

Ultrasound is highly specific in diagnosing compensated cirrhosis in chronic hepatitis C patients in real world clinical practice.

Ultrasound is routinely used during the evaluation of liver cirrhosis. Inter-observer variability is considered a major drawback. This retrospective study investigated the accuracy of ultrasound in diagnosing compensated cirrhosis (i.e., modified Knodell F3, F4) in chronic hepatitis C (CHC) patients in real world clinical practice. Consecutive treatment-naive CHC patients who underwent liver biopsy (LB) prior to interferon therapy from 1997 to 2010 were enrolled. Ultrasound was performed by 30 hepatologists prior to LB. Ultrasound-identified cirrhosis was defined as small liver size, nodular liver surface and coarse liver parenchyma. LB was used as a reference, and the diagnostic accuracy of ultrasound was assessed and compared. Fibrosis was scored according to the modified Knodell classification. A cohort comprising 1738 patients, including 922 men and 816 women with a mean age of 52.5 years, was analyzed in the present study. The distribution of the patients' modified Knodell scores was F0 = 336, F1 = 489, F2 = 165, F3 = 315, F4 = 433. Ultrasound-identified cirrhosis was noted in 283 patients. Using ultrasound-identified cirrhosis to predict compensated cirrhosis, the sensitivity was 34.0%, the specificity was 97.1%, the positive predictive value was 89.8%, the negative predictive value was 66.1%, the positive likelihood ratio was 11.6, and the negative likelihood ratio was 0.68. The area under the ROC curve (AUROC) was 0.66.Despite being affected by inter-observer variability, ultrasound is highly specific in diagnosing compensated cirrhosis in CHC patients in real world clinical practice. However, the sensitivity is low.

Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients.

BACKGROUND: Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted. AIMS: We investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients. METHODS: A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings. RESULTS: For the subgroup of 684 patients without cirrhosis, Kaplan-Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox's proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05-3.43, P = 0.03). CONCLUSIONS: Diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

A scoring system to predict HBsAg seroclearance in hepatitis B and C coinfected patients treated with interferon and ribavirin in an Asian cohort.

Current guidelines recommend that patients with hepatitis B virus-hepatitis C virus (HBV-HCV) coinfection be treated with direct anti-viral agents (DAAs). Compared with DAAs, pegylated interferon (PEG-IFN) and ribavirin therapy has the advantages of treating both viruses while maintaining an acceptable HCV sustained virological response (SVR) rate (70-80%) in Asian cohorts. In this study, we aimed to develop a simple scoring system to predict hepatitis B surface antigen (HBsAg) seroclearance in these patients. We enrolled 201 patients with HCV-HBV coinfection after IFN and ribavirin therapy. The study population was randomly allocated into derivation and validation sets in a 1:1 ratio. In the derivation cohort, multivariate analysis by Cox regression analysis revealed that HBsAg seroclearance was associated with age > 60 years (HR: 5.55, 95% CI: 1.68-18.37, P = .005), male gender (HR: 3.88, 95% CI: 1.18-12.80, P = .03), and qHBsAg level ≤100 IU/ml (HR: 4.87, 95% CI: 1.20-19.74, P = .03). Regression coefficients were used to build up a risk score, and the accuracy of the risk score was evaluated by using the area under the receiver operating characteristic curve (AUROC). The patients were classified into either a low-risk group or high-risk group based on the risk scores. Twenty-three (23.0%) patients in the derivation cohort and 30 (29.7%) patients in the validation cohort showed HBsAg seroclearance with an AUROC of 71.8%, sensitivity of 65.22%, and specificity of 75.32%. In the validation cohort, the 5-year HBsAg seroclearance incidence rates were 23.4% in the low-risk category and 43.8% in the high-risk category (HR = 2.21; 95% CI, 1.04-4.68, P = .04)The risk scoring system could be used to predict HBsAg seroclearance for HCV-HBV coinfected patients treated with IFN and ribavirin.

Rebound thymic hyperplasia after liver transplantation for a child with biliary atresia; a case report.

The thymus gland possesses the ability to regrow in children leading to a newly developed anterior mediastinal mass. This condition may represent a rebound phenomenon during recovery from a stressful event such as post-chemotherapy and hence was described as RTH. RTH after LT has not been well documented. We are reporting an infant with BA who underwent LT and presented with a symptomless anterior mediastinal mass, detected on follow-up imaging 6 months thereafter. Surgical partial excision was performed to rule out other differential diagnoses of a solid mass in the anterior mediastinum of an infant particularly lymphoma-that may arise as post-transplant lymphoproliferative disorder-and teratoma, as well as the other aggressive lesions such as thymoma and thymic carcinoma. The final pathological analysis revealed true thymic hyperplasia, consistent with RTH. The diagnosis of RTH should be considered for a child presenting by anterior mediastinal mass after LT.

APRI and FIB-4 in the evaluation of liver fibrosis in chronic hepatitis C patients stratified by AST level.

BACKGROUND AND AIM: The aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level. METHODS: This retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997-2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST≤37 IU/L (N = 132), 37148 IU/L (N = 346). RESULTS: 436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST≤37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST≤37 IU/L; 1.1 and 2.2, respectively, in patients with 37148 IU/L. CONCLUSIONS: We provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.

The surgical challenges of salvage living donor liver transplantation for Hepatocellular carcinoma; The cumulative experience of 100 cases - A retrospective cohort study and a propensity score analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasingly managed by liver resection first then salvage liver transplantation in case of recurrence within accepted criteria. Many reports compared the safety of the salvage against the primary surgery in the setting of deceased donation but the difference in case of living donation is not sufficiently defined. Salvage living donor liver transplantation (SLDLT) is believed to be a more challenging surgery than primary living donor liver transplantation (PLDLT) due to operative field adhesions, in addition to the inherent difficulties particularly short vasculobiliary stumps. In this report, we compared both pathways from a surgical perspective in a homogenous LDLT-only cohort. MATERIALS AND METHODS: Over 15 years, 448 LDLTs for HCC were performed in a single liver transplant institution in Taiwan, including PLDLT (n = 348) and SLDLT (n = 100). A retrospective comparative review of the surgical outcomes of both pathways using a propensity score matching model (1-1, 100 pairs) was performed with adjustment for age, Child score and MELD score. The surgical outcome and survival were compared across 2 time eras. RESULTS: The operative data showed that SLDLT surgery encountered more extensive adhesions (57% vs. 0%, p < 0.001), longer operative duration (650 vs. 618 min, p=0.04), and was followed by more incidence of re-exploration (16% vs. 5%, p=0.01), than the PLDLT surgery. There was no significant difference regarding the incidence of in-hospital mortality, vascular and biliary complications, or overall survival (OS). The 1-year OS of SLDLT was inferior to PLDLT in the first 50 cases (90% vs. 98%, p=0.03), then the same OS was found in the 2nd 50 cases (96% vs. 96%, p=0.9). CONCLUSIONS: The SLDLT surgery is a demanding lengthy procedure with extensive adhesions and possibility of frequent re-explorations. Significant case load and high centre volume are important factors for safe practice of SLDLT and better cumulative OS.

Increased expression of senescence-associated cell cycle regulators in the progression of biliary atresia: an immunohistochemical study.

AIMS: Cellular senescence plays a role in tumour suppression and in the pathogenesis of various non-neoplastic diseases, including primary biliary cholangitis and other adult cholangiopathies. Less is known about the role of cellular senescence in cholangiopathies in children. With that in mind, we examined the expression of senescence-associated cell cycle regulators in biliary atresia, the most common form of paediatric obliterative cholangiopathy. METHODS AND RESULTS: The expression of senescence-associated cell cycle regulators (p16Ink4a and p21WAF1/Cip1 ) and a ductular reaction related marker (neural cell adhesion molecule: NCAM) was examined in bile ducts and bile ductules in liver samples taken from the patients with biliary atresia [n = 80; including 23 samples at the time of the Kasai procedure (KP) and 63 obtained from the explanted liver (LT) (six cases with samples at both surgical stages of disease)] and from appropriate controls (n = 17). The degree of ductular reaction and cholestasis was significantly more extensive in LT than KP (P < 0.01). The expression of p16INK4a and NCAM was significantly more extensive in bile ducts and bile ductules in ductular reaction in both KP and LT compared to controls and in LT compared to KP (P < 0.05). The expression of p21WAF1/Cip1 was significantly more extensive in bile ducts and bile ductules in KP compared to both LT and controls (P < 0.01). CONCLUSIONS: Cellular senescence may play a role in the progression of bile duct loss in biliary atresia in a manner similar to that of adult cholangiopathies.

The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients.

BACKGROUND & AIMS: Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. METHODS: A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. RESULTS: Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. CONCLUSIONS: Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.

Liver Transplantation for High Risk Hepatocellular Carcinoma After Liver Resection: A Sequential or Salvage Approach?

BACKGROUND Liver transplantation (LT) is the best radical treatment of hepatocellular carcinoma (HCC). Salvage liver transplantation (SalvLT) provides good outcomes for recurrent HCC cases after initial curative liver resection (LR). However, the salvage strategy is not feasible in all situations due to aggressive recurrences. Recently, sequential liver transplantation (SeqLT) was proposed for cases that show adverse pathological features after LR, thus LT is performed pre-emptively before recurrence. In this report, we compared the outcomes of SalvLT and SeqLT for surgical treatment of HCC. MATERIAL AND METHODS One hundred and ten cases underwent LR for HCC, then were subjected to either SalvLT (n=91) or SeqLT (n=19), from January 2001 to December 2015. For cases that underwent several LR before LT, we collected the data of the last LR before transplantation. A comparison was made according to pre- and post-transplant clinical and pathological variables. Survival analysis and comparison between both pathways are provided. RESULTS The median interval (months) between LR and LT for the SeqLT group and the SalvLT group were 9.6 and 22.2, respectively. (p=0.01). The LR histopathological features were similar in both groups. In the SalvLT group, the histopathological comparison between the criteria of last LR and the criteria of liver explants revealed that 14 cases advanced from stage I to stage II, one cases from stage I to stage IIIa, one case from stage I to stage IIIb, one case from stage I to stage IIIc, three cases from stage II to stage IIIb and one case from stage II to stage IIIc. The overall rate of pathological upstaging in the SalvLT group was 27%. The incidence of post-transplant HCC recurrence was 5% (1/19) and 11% (10/91) for the SeqLT and SalvLT groups, respectively (p=0.4). The incidence of post-LT in-hospital mortality was 0% among the SeqLT group and 2% (2/91) among the SalvLT group. The estimated rates of five-year overall survival and cancer specific survival for the SeqLT group versus the SalvLT group were (92.3% versus 87.6%; p=0.4) and (92.3% versus 91.9%; p=0.7), respectively. CONCLUSIONS The SeqLT approach might be associated with low incidence of cancer recurrence, better overall survival, and less operative mortality. Another possible benefit is the avoidance of aggressive non-transplantable HCC recurrences. More studies and/or randomization are required for highre evidence conclusions.

TFE3-rearranged hepatic epithelioid hemangioendothelioma-a case report with immunohistochemical and molecular study.

A recurrent YAP1-TFE3 gene fusion has been identified in WWTR1-CAMTA1-negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3-rearranged hepatic epithelioid hemangioendothelioma in a 39-year-old Taiwanese woman. Computed tomography scan revealed multifocal, ill-defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern. One component was composed of dilated and well-formed blood vessels lined by epithelioid cells with abundant eosinophilic cytoplasm, mimicking an alveolar pattern, whereas the other component was composed of cords and single cells, featuring intracytoplasmic vacuoles, separated by a myxoid stroma. The tumor cells showed vesicular nuclei and small indistinct nucleoli with mild to moderate cytologic atypia. Most tumor cells showed factor VIII, CD34, CD31, and TFE3 positivity in immunohistochemical study. Fluorescence in situ hybridization analysis for the tumor cells exhibited TFE3 gene rearrangement. The patient is currently alive, and no post-operative tumor recurrence developed during a 13-year follow-up. Awareness of this rare vasoformative variant and identification of the gene rearrangement would be helpful on differential diagnosis with other high-grade carcinoma and angiosarcoma of liver.