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This study verified whether radical treatment for hepatocellular carcinoma (HCC) oligo-recurrence after liver transplantation conveys survival benefits. A retrospective study of 144 patients with posttransplant HCC recurrence was performed. Propensity score matching was performed to adjust for baseline covariates between patients who received radical and palliative treatments. The primary endpoint was postrecurrence survival. A total of 50 patients (35%) received radical treatment for recurrence, and 76 (53%) and 18 (13%) patients received palliative and supportive treatments, respectively. Compared with the radical group, patients who received palliative treatment had more early recurrences (time from transplant 17 versus 11 months; P = 0.01) and more extensive disease in terms of tumor numbers (1 versus 4; P < 0.001), size of largest tumor (1.8 versus 2.5 cm; P = 0.046), numbers of involved organs (interquartile range [IQR], 1-1 versus 1-2; P = 0.02), and alpha-fetoprotein (AFP) level (7 versus 40 ng/mL; P = 0.01). Multivariate Cox regression analysis revealed that early recurrence (time from transplant hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P = 0.001), larger recurrent tumor (HR, 1.12; 95% CI, 1.03-1.23; P = 0.01), liver recurrence (HR, 1.84; 95% CI, 1.17-2.90; P = 0.01), and log 10 AFP level at recurrence (HR, 1.27; 95% CI, 1.07-1.52; P = 0.01) predicted poor survival. Mammalian target of rapamycin inhibitor (HR, 0.331; 95% CI, 0.213-0.548; P < 0.001) and radical treatment (HR, 0.342; 95% CI, 0.213-0.548; P < 0.001) were associated with improved survival. After 2-to-1 propensity score matching for covariates, the 50 patients who received curative treatment survived significantly longer than the 25 matched patients who received palliative treatment (median survival time, 30.9 ± 2.4 versus 19.5 ± 3.0 months; P = 0.01). Radical treatment conveys survival benefits to HCC oligo-recurrence after liver transplantation., (Copyright © 2021 American Association for the Study of Liver Diseases.)

Objective: The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR)., Background: The standard GRWR in LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients., Methods: Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 2: 0.6%0.8%)., Results: There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R2 = 0.834) and these figures differed within a ± 10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was <35 years and steatosis >10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS): 5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients [24/26 (92.3%)] survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis., Conclusions: Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain., Methods: A propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed., Results: A consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively)., Conclusions: LT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2020.03.09). Dr. ACYC and Dr. CML serve as unpaid editorial board members of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2021 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Introduction: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics., Methods: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed., Results: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25-1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41-55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state., Discussion: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).

Introduction: Entecavir (ETV) showed short-term efficacy and safety in HBsAg-positive kidney transplant recipients (KTRs), but long-term data are lacking., Methodology: We retrospectively reviewed 30 HBsAg-positive KTRs who received ETV during 2007-2017., Results: Eighteen treatment-naïve (Group I) and 12 lamivudine-resistant (Group II) patients received ETV for 48.4 ± 35.2 and 66.0 ± 26.0 months, respectively. Both groups show significant HBV DNA decline, but Group I achieved earlier undetectability after 11.9 ± 9.6 months (compared with 28.8 ± 24.2 months in Group II, P = .033). Group I showed higher rates of undetectable HBV DNA (89%, 94%, 94%, 100%, and 100% at 12, 24, 36, 48, and 60 months, respectively, compared with 25%, 50%, 50%, 91%, and 91% in Group II, P = .003). ALT normalized after 6.0 ± 1.9 and 6.8 ± 2.1 months in Group I and Group II, respectively. Four patients (33.3%) in Group II developed drug resistance (2 had persistent viraemia and 2 had virological breakthrough, at 40.3 ± 15.0 months). Group II showed higher liver stiffness after 5 years (7.7 ± 4.1 kPa, compared with 5.0 ± 1.6 kPa in Group I, P = .046) and incidence of cirrhosis (4 patients [33.3%], compared with 1 [5.6%] patient in Group I, P = .049). Two patients (one in each group) developed hepatocellular carcinoma. Renal allograft function remained stable during follow-up of 63.2 ± 33.4 months for both groups. There was no difference in patient and graft survival between two groups at 5 years (P = .62 and .36, respectively)., Conclusion: ETV showed favorable long-term efficacy and tolerability in treatment-naïve KTRs. One-third of lamivudine-resistant subjects showed non-response or viral breakthrough after ETV treatment., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking., Aim: To evaluate the impact of small-for-size liver grafts on medium-term and long-term graft survival in adult to adult LDLT., Methods: A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted., Results: This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies., Conclusion: SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: We sought to develop a nomogram for the prediction of tumor recurrence after resection of hepatocellular carcinoma (HCC) within the Milan criteria., Method: Consecutive HCC patients admitted for hepatectomy between 1994 and 2014 were enrolled in this study. Patients were excluded if they had recurrent HCC or tumors beyond the Milan criteria. Patients were randomized and assigned to the derivation and validation sets in a 1:1 ratio. Independent factors for disease-free survival were identified using the Cox regression model. A nomogram was derived and validated with the receiver-operating characteristic (ROC) and calibration curves., Results: There were 617 eligible patients included in the analysis. The median age was 59 years, 481 were male, and 87.8% of the patients were hepatitis B virus carriers. The median follow-up was 68.7 months. The 5-year overall survival rate was 73.3% and HCC recurrence was detected in 55% of the patients. In the derivation set, a nomogram was constructed based on the seven independent factors for disease-free survival: age, alpha-fetoprotein, preoperative prothrombin time, magnitude of hepatectomy, postoperative complication, number of tumor nodules, and presence of microvascular invasion. A satisfactory discrimination ability was observed in both the derivation and validation sets (c-stat 0.672 and 0.665, respectively). The calibration plot yielded agreement between the predicted and observed outcomes, using the derived nomogram., Conclusion: A validated nomogram quantifies the risk of recurrence after hepatectomy for HCC within the Milan criteria, and assists with the planning of individual postoperative surveillance protocols.

Background: Previous studies comparing outcomes of hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) showed conflicting results, and most studies measured survival outcomes from the time of liver transplantation (LT)., Method: This retrospective study was aimed to evaluate the long-term outcomes of HCC patients listed for LT using intention-to-treat (ITT) and propensity score matching (PSM) analyses. Clinicopathological data were retrieved from a prospectively collected database., Results: From 1995 to 2014, 375 HCC patients were listed for LT. ITT-LDLT group had 188 patients, whereas ITT-DDLT group had 187 patients. Twenty-seven patients (14.4%) and 122 patients (65.2%) were delisted from LDLT and DDLT waitlist, respectively. The 1-, 3- and 5-year overall survival rates were significantly better in ITT-LDLT group than ITT-DDLT group (94.1 vs. 77.5%, 81.4 vs. 48.7% and 75.9 vs. 40.8%). High alphafetoprotein (AFP) and ITT-DDLT treatment arm were independent poor prognostic factors affecting overall survival. LDLT group (n = 161) had more young patients, poorer liver function, higher AFP, more tumors outside Milan/UCSF criteria, when compared with DDLT group (n = 85). After PSM, the 1-, 3- and 5-year overall (95.4 vs. 98.5%, 80.0 vs. 92.3% and 73.4 vs. 84.4%) and recurrence-free (87.7% vs. 90.8%, 76.9% vs. 83.1% and 72.2% vs. 81.5%) survival rates were comparable between the matched LDLT and the matched DDLT group, respectively., Conclusion: Survival benefit of LDLT was observed for HCC patients with ITT analysis. Despite a more advanced tumor stage, overall and recurrence-free survival rates were comparable between LDLT and DDLT using PSM analysis.

Background: Liver transplantation (LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma (HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive agents., Aim: To develop a scoring system to predict HCC recurrence after LT in an Asian population., Methods: Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a 60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic curve., Results: In total, 330 patients were eligible for analysis (183 in training and 147 in validation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were 78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [ P = 0.012, hazard ratio (HR) 2.92], sum of maximum tumor size and number ( P = 0.013, HR 1.15), and salvage LT ( P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power (c-stat 0.748 and 0.85, respectively, in the training and validation sets). With the derived scores, patients were classified into low- (0-9), moderate- (> 9-14), and high-risk groups (> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54% (c-stat 0.67) and 4%, 22%, 62% (c-stat 0.811), accordingly. The risk stratification model was validated with chi-squared goodness-of-fit test ( P = 0.425)., Conclusion: A validated predictive model featuring alpha-fetoprotein, salvage LT, and the sum of largest tumor diameter and total number of tumor nodule provides simple and reliable guidance for individualizing postoperative surveillance strategy., Competing Interests: Conflict-of-interest statement: None of the authors has any conflict of interest.

In patients with end-stage liver disease, hypogonadism and erectile dysfunction are often seen. This study was to determine the incidence of erectile dysfunction before and after liver transplantation (LT) with correlation to change in sex hormone levels from a Chinese cohort. This prospective longitudinal study was registered with The University of Hong Kong Clinical Trials Centre (HKUCTR-1563). The Institutional Review Board approval number is UW-12-273. The study period was from January 2012 to December 2016. Adult male patients with end-stage liver disease enlisted for LT were recruited on informed written consent. All recruited patients were to complete a cross-sectional cohort questionnaire-International Index of Erectile Function, version 5 (IIEF5)-and to receive serum sex hormone checks before and after LT. Twenty-eight patients who underwent LT were included in the analysis. The included patients had significantly reduced prolactin ( p < .001) and 17-beta-estradiol ( p = .024) after LT. There was also a significant drop of IIEF5 score at 1 month after LT, but the score returned to pre-LT level at 6 months. This study demonstrated that there was improvement in sex hormone levels after LT, namely, normalization of estradiol level and lowering of prolactin and progesterone levels. However, improvement in sex hormone levels did not translate into improvement of erectile dysfunction.

Background: Whether primary liver transplantation (PLT) or upfront curative treatment with salvage liver transplantation (SLT) is a better treatment option for early hepatocellular carcinoma (HCC) is controversial. This study aims to compare the long-term survival starting from the time of primary treatment between the two approaches for early HCC using propensity score matching (PSM) analysis., Methods: From 1995 to 2014, 175 patients with early HCC undergoing either PLT (n = 149) or SLT (n = 26) were retrospectively reviewed in a prospectively collected database. Patients' demographic data, tumor characteristics, short-term and long-term outcome were compared between two groups after PSM., Results: After matching, the baseline characteristics were comparable between mPLT group (n = 45) and mSLT group (n = 25). The tumor recurrence rate after transplant was significantly higher in mSLT group than mPLT group (28% vs. 15.6%). Calculating from the time of primary treatment, the 1, 3, and 5-year overall survival rates were comparable between mPLT group (97.8%, 91.1% and 86.3%) and mSLT group (100%, 95% and 85%). However, the 1, 3, and 5-year recurrence-free survival rates were significantly better in mPLT group than mSLT group (95.6% vs. 90%, 86.6% vs. 80% and 84.3% vs. 70%). SLT approach and high pre-treatment serum alpha-fetoprotein level (>200 ηg/mL) were poor prognostic factors for recurrence-free survival after transplant., Conclusions: PLT may be a better treatment option for early HCC, whereas SLT approach for HCC should be cautiously considered under the circumstance of organ shortage., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background & Aims: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations., Methods: We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model., Results: We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log 10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log 10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log 10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log 10 IU/mL, 95% CI, 3.73-4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I 2  = 97.49%)., Conclusion: In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Pneumocystis pneumonia (PCP) is a common opportunistic infection caused by Pneumocystis jirovecii. Its incidence at 2 years or more after liver transplant (LT) is < 0.1%. PCP-related spontaneous pneumothorax and/or pneumomediastinum is rare in patients without the human immunodeficiency virus, with an incidence of 0.4-4%., Case Presentation: A 65-year-old woman who had split-graft deceased-donor LT for primary biliary cirrhosis developed fever, dyspnea and dry coughing at 25 months after transplant. Her immunosuppressants included tacrolimus, mycophenolate mofetil, and prednisolone. PCP infection was confirmed by molecular detection of Pneumocystis jirovecii,in bronchoalveolar lavage. On day-10 trimethoprim-sulphamethoxazole, her chest X-ray showed subcutaneous emphysema bilaterally, right pneumothorax and pneumomediastinum. Computed tomography of the thorax confirmed the presence of right pneumothorax, pneumomediastinum and subcutaneous emphysema. She was managed with 7-day right-sided chest drain and a 21-day course of trimethoprim-sulphamethoxazole before discharge., Conclusion: Longer period of PCP prophylaxis should be considered in patients who have a higher risk compared to general LT patients. High index of clinical suspicion, prompt diagnosis and treatment with ongoing patient reassessment to detect and exclude rare, potentially fatal but treatable complications are essential, especially when clinical deterioration has developed.

Background: To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030., Methods: From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed., Results: A total of 11 309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001)., Conclusion: Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)