Yu-Chao Wang

The Preference for Anterior Approach Major Hepatectomy: Experience Over 3 Decades and a Propensity Score-Matching Analysis in Right Hepatectomy for Hepatocellular Carcinoma.

AbstractSurgical treatment for primary hepatocellular carcinoma (HCC) has progressed enormously over time. The aim of this study was to analyze the evolution of surgical techniques and outcomes of patients undergoing major right hepatectomy (RH) over the last few decades.A retrospective review of 557 consecutive patients who had undergone RH for HCC between January 1982 and December 2011 was performed. Patients were categorized into subgroups and analyzed according to period and surgical approach to hepatectomy. Based on a propensity score-matching model, the surgical approach in patients in the second period was also analyzed in terms of anterior approach (AA) and conventional approach (CA)-RH.Tumor factors remained the most important prognostic factors related to postoperative HCC recurrence throughout the 2 periods examined in this study. Comparison of patients selected by a propensity score-matching model showed that AA-RH led to significantly better outcomes including recurrence-free survival (RFS) (P = 0.011) and overall survival (OS) (P = 0.012) in patients with HCC as compared with CA-RH. The 5-year RFS and OS were 33.4% and 52.2% after AA-RH, and 21.0% and 36.5% after CA-RH.Major hepatectomy has evolved into a safe procedure that can be performed with confidence. RH by an AA has shown several advantages over CA-RH, and can thus be recommended as the standard procedure for liver resection in patients who require right hepatectomy.

Adult Living Donor Liver Transplantation Across ABO-Incompatibility

Abstract The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT). ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation. Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ⩽64, liver transplantation was directly performed and rituximab (375 mg/m2) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375 mg/m2) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids. Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (P = 0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, P = 0.009). In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.

Inhibition of allogenic T-cell cytotoxicity by hepatic stellate cell via CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in vitro.

BACKGROUND The liver is considered to be an immune-privileged organ. Several types of liver cells have been implicated in the induction of immunologic tolerance. Hepatic stellate cells (HSCs) seem to participate in hepatic fibrosis and to display immunological properties. MATERIALS AND RESULTS In this study, HSCs isolated from C3H mice were highly positive for GFAP (98.4%) and α-SMA (95.4%). After stimulation by interferon-γ (IFN-γ), HSCs were more active in morphology with enhanced expression of H2-K(K), I-A(K), CD80, and CD54, similar to mature myelogenic dendritic cells (MDCs). Through allogeneic stimulation, C3H HSCs induced proliferation of both CD8(+) and CD4(+) T cells in B6 mice. However, the T cells activated by allogeneic HSCs produced less INF-γ, interleukin (IL)-4, IL-10, and IL-17, but large amount of transforming growth factor-β. These T cells expressed immunoregulatory rather than effector functions. Naïve T cells stimulated by allogeneic HSCs expressed Foxp3 compared with MDCs (8.67% vs 2.14%, P < .05). CD8(+) T cells activated by HSCs lost their allogeneic cytotoxicity, and CD4(+) T cells activated in this fashion suppressed the allogeneic cytotoxicity of CD8(+) T cells activated by MDCs. CONCLUSION HSCs seem to act as liver-resident antigen-presenting cells instructing the generation of Foxp3(+) regulatory T cells, a property suggestion of induction of immunologic tolerance.

Validation of the Model for End-Stage Liver Disease Score Criteria in Urgent Liver Transplantation for Acute Flare Up of Hepatitis B

AbstractAcute flare up of hepatitis B in noncirrhotic liver with rapid liver function deterioration is a critical condition. This flare up of hepatitis B may be subsided under medical treatments, otherwise urgent liver transplantation is needed. However, the necessity of urgent liver transplantation is hard to decide. In this institute, the indications of urgent liver transplantation for acute flare up of hepatitis B in noncirrhotic liver were settled according to the model for end-stage liver disease (MELD) scores: once upon MELD scores ≥35 (criterion 1) or MELD score < 35 at beginning and increased in the subsequent 1 to 2 weeks (criterion 2). This study was to examine whether MELD score criteria for liver transplantation were valid in such an urgent condition. Eighty-three patients having acute flare up of hepatitis B virus with total bilirubin ≥17.5 mg/dL were included in this study. Among 83 patients, 20 patients met criterion 1. Five patients were transplanted and 15 patients died of liver failure with a median survival of 17 days. Fifty-one patients met criterion 2. Nineteen were transplanted, 30 patients died of liver failure with a median survival of 23.5 days, and 2 patients recovered from this critical condition. The other 12 patients did not meet criteria 1 and 2, and urgent liver transplantation was spared although 5 patients needed liver transplantation in subsequent 2 to 3 months. Therefore, the sensitivity of MELD score criteria for urgent liver transplantation was 100% and specificity was 85.7%. In conclusion, determination of urgent liver transplantation for hepatitis B with acute liver failure is crucial. MELD score criteria are valid to make a decision of urgent liver transplantation for hepatitis B patients with acute flare up and liver failure.

Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

Abstract Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population. From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports. Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population. Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis

Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management.

Prognostic Impact and Risk Factors of Low Body Mass Index in Patients Undergoing Liver Transplantation

We aimed to investigate the effect of body mass index (BMI) on the overall survival rates and to identify the risk factors associated with adverse outcomes. A total of 381 adult‐to‐adult living donor liver transplantations performed were retrospectively analyzed. These patients were classified according to the BMI categories established by the World Health Organization: The underweight group (BMI<18.5 kg/m2) and the non‐underweight group (BMI≥18.5 kg/m2). The underweight group had significantly worse outcomes, compared with that of the non‐underweight group (5‐year overall survival: 45.6% vs 74.6%, P<.001). Underweight patients with CD4/CD8 ratio <1.4 had a significant worse prognosis, compared with those with CD4/CD8 ratio ≥1.4. (The 1‐, 3‐, and 5‐year overall patient survival rates in both groups were 71.0% vs 20%, 58.9% vs 0%, and 53.6% vs 0%, respectively, P=.002.) In the multivariate analysis, only CD4/CD8 ratio <1.4 was an independent poor prognostic factor (hazard ratio=7.063, 95% confidence interval=1.329‐37.547, P=.022).

Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease

Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n = 60) and telbivudine-replacement (n = 60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p < 0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.

Effect of Prophylactic Antifungal Protocols on the Prognosis of Liver Transplantation: A Propensity Score Matching and Multistate Model Approach

Background. Whether routine antifungal prophylaxis decreases posttransplantation fungal infections in patients receiving orthotopic liver transplantation (OLT) remains unclear. This study aimed to determine the effectiveness of antifungal prophylaxis for patients receiving OLT. Patients and Methods. This is a retrospective analysis of a database at Chang Gung Memorial Hospital. We have been administering routine antibiotic and prophylactic antifungal regimens to recipients with high model for end-stage liver disease scores (>20) since 2009. After propensity score matching, 402 patients were enrolled. We conducted a multistate model to analyze the cumulative hazards, probability of fungal infections, and risk factors. Results. The cumulative hazards and transition probability of “transplantation to fungal infection” were lower in the prophylaxis group. The incidence rate of fungal infection after OLT decreased from 18.9% to 11.4% (p = 0.052); overall mortality improved from 40.8% to 23.4% (p < 0.001). In the “transplantation to fungal infection” transition, prophylaxis was significantly associated with reduced hazards for fungal infection (hazard ratio: 0.57, 95% confidence interval: 0.34–0.96, p = 0.033). Massive ascites, cadaver transplantation, and older age were significantly associated with higher risks for mortality. Conclusion. Prophylactic antifungal regimens in high-risk recipients might decrease the incidence of posttransplant fungal infections.