The Risk of Going Small: Lowering GRWR and Overcoming Small-For-Size Syndrome in Adult Living Donor Liver Transplantation.

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 ±â€Š10%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.

Long-term data on entecavir treatment for treatment-naive or lamivudine-resistant chronic hepatitis B infection in kidney transplant recipients.

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.

Long-Term Survival Outcome Between Living Donor and Deceased Donor Liver Transplant for Hepatocellular Carcinoma: Intention-to-Treat and Propensity Score Matching Analyses.

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.

Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report.

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.

Long-term survival comparison between primary transplant and upfront curative treatment with salvage transplant for early stage hepatocellular carcinoma.

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 Î·g/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.

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

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.

Comparable short- and long-term outcomes in deceased-donor and living-donor liver retransplantation.

BACKGROUND AND PURPOSE: There is a big controversy over liver retransplantation, the only life-saving treatment for patients with a failing or failed liver graft. This retrospective study tried to determine if living-donor liver retransplantation (re-LDLT) is a justifiable alternative to deceased-donor liver retransplantation (re-DDLT). METHODS: Anonymous data of liver transplant patients from January 2000 to April 2016 were reviewed. Recipients of retransplantation were divided into the re-DDLT and re-LDLT groups. The groups were compared in demographic characteristics, pre-retransplant and intraoperative details, and short- and long-term outcomes. Risk for living donors was examined. RESULTS: Twenty-nine patients had 33 re-DDLTs and 15 patients received re-LDLT. The re-LDLT group had lighter grafts (525 vs. 1295 g, p ≤ 0.001), a smaller ratio of graft weight to recipient standard liver volume (56.98 vs. 107.7%, p ≤ 0.001), and shorter cold ischemia (106 vs. 451 min, p ≤ 0.001). The groups were otherwise comparable. Two patients in the re-DDLT group had Grade-5 complication. The groups were similar in patient survival (p = 0.326) and graft survival (p = 0.102). No living donors died, but three of them developed Grade-1 complications. CONCLUSION: With the required expertise, re-LDLT can produce results comparable to those of re-DDLT while keeping donor risk at bay. In places where the demand for deceased-donor liver grafts far outstrips supply, re-LDLT can be considered as an alternative to re-DDLT if the expertise is available and if the potential recipient benefits can balance out the potential donor risks.

A new formula for estimation of standard liver volume using computed tomography-measured body thickness.

The objective of this article is to derive a more accurate and easy-to-use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25-13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36-3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm3 ) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R2 , 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C-statistic, 0.79; 95% CI, 0.69-0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT-measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113-1122 2017 AASLD.

Liver transplantation for severe alcoholic hepatitis-The CON view.

In patients with severe alcoholic hepatitis (AH) who have failed medical therapy, liver transplantation (LT) remains a controversial therapeutic option. This is exemplified by the fact that most of these patients will not have had a period of abstinence prior to consideration for transplantation. Both abstinence before transplantation and the duration of abstinence are important predictors of post-transplant relapse. Furthermore, relapse after transplantation has been associated with accelerated graft injury and increase mortality. Recent pilot studies have demonstrated a benefit in short-term survival with early transplantation in highly selected small number of patients compared to matched controls. The results of these studies raises the possibility of extending graft allocation to these subjects. Despite stringent assessment and a multi-tiered approach to selecting out patients for transplantation, the relapse rate was not insignificant at 12%. As the long-term outcome remains unclear, further relapses with time can still occur. These studies also highlight the fact that the overwhelming majority of subjects with severe AH who are non-responsive to medical therapy are not suitable for LT. Indeed, further large-scale multicentre prospective studies with long-term follow-up are required to confirm the preliminary findings.

Comparable Short- and Long-term Outcomes in Living Donor and Deceased Donor Liver Transplantations for Patients With Model for End-stage Liver Disease Scores ≥35 in a Hepatitis-B Endemic Area.

OBJECTIVE: To evaluate if living donor liver transplantation (LDLT) should be offered to patients with Model for End-stage Liver Disease (MELD) scores ≥35. BACKGROUND: No data was available to support LDLT of such patients. METHODS: Data of 672 consecutive adult liver transplant recipients from 2005 to 2014 at our center were reviewed. Patients with MELD scores ≥35 were divided into the deceased donor liver transplantation (DDLT) group and the LDLT group and were compared. Univariate analysis was performed to identify risk factors affecting survival. RESULTS: The LDLT group (n = 54) had younger (33 yrs vs 50 yrs, P < 0.001) and lighter (56 Kg vs 65 Kg, P = 0.004) donors, lighter grafts (627.5 g vs 1252.5 g, P < 0.001), lower graft-weight-to-recipient-standard-liver-volume rates (51.28% vs 99.76%, P < 0.001), shorter cold ischemic time (106.5 min vs 389 min, P < 0.001), and longer operation time (681.5 min vs 534 min, P < 0.001). The groups were comparable in postoperative complication, hospital mortality, and graft survival and patient survival at one year (88.9% vs 92.5%; 88.9% vs 94.7%), three years (87.0% vs 86.9%; 87.0% vs 88.8%), and five years (84.8% vs 81.8%; 84.8% vs 83.3%). Univariate analysis did not show inferior survival in LDLT recipients. CONCLUSIONS: At centers with experience, the outcomes of LDLT can be comparable with those of DDLT even in patients with MELD scores ≥35. When donor risks and recipient benefits are fully considered and balanced, an MELD score ≥35 should not be a contraindication to LDLT. In Hong Kong, where most waitlisted patients have acute-on-chronic liver failure from hepatitis B, LDLT is a wise alternative to DDLT.

Liver transplantation and hepatitis B virus infection: towards an immunoglobulin-free antiviral treatment after transplantation.

PURPOSE OF REVIEW: This article provides an update on the latest development on deploying oral nucleosides in an immunoglobulin-free regime against hepatitis B virus (HBV) recurrence after liver transplantation. RECENT FINDINGS: Entecavir and tenofovir are the two newer oral nucleosides that are associated with a low virological rebound rate at less than 2% at 5 years. As a result, they have been applied as standalone treatment against HBV recurrence after liver transplantation without immunoglobulin. Recent evidence has shown that a hepatitis B surface antigen seroclearance rate of 86% and 91% after 1 and 2 years was achievable with entecavir monotherapy. Moreover, none of the patients had histological graft damage because of HBV recurrence and an overall survival over 80% at 7 years has been reported. SUMMARY: With newer and more potent oral nucleos(t)ide (NA) available, a hepatitis B immune globulin-free regimen after liver transplantation has become safe and feasible for suppression of HBV recurrence after liver transplantation, and for avoidance of HBV-related graft complications.

Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors.

Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.

New insights after the first 1000 liver transplantations at The University of Hong Kong.

BACKGROUND/OBJECTIVE: One thousand liver transplantations have been performed at the only liver transplant center in Hong Kong over a period of 22 years, which covered the formative period of living donor liver transplantation. These 1000 transplantations, which marked the journey of liver transplantation from development to maturation at the center, should be educational. This research was to study the experience and to reflect on the importance of technical innovations and case selection. METHODS: The first 1000 liver transplantations were studied. Key technical innovations and surgical therapeutics were described. Recipient survival including hospital mortality was analyzed. Recipient survival comparison was made for deceased donor liver transplantation and living donor liver transplantation indicated by hepatocellular carcinoma and other diseases. RESULTS: Among the 1000 transplantations, 418 used deceased donor grafts and 582 used living donor grafts. With the accumulation of experience, hospital mortality improved to < 2% in the past 2 years. In the treatment of diseases other than hepatocellular carcinoma, living donor liver transplantation was superior to deceased donor liver transplantation, with a 10-year recipient survival around 90%. CONCLUSION: Transplant outcomes have been improving consistently over the series, with a very low hospital mortality and a predictably high long-term survival.

Outcomes of endo-radiological approach to management of bile leakage after right lobe living donor liver transplantation.

BACKGROUND AND AIM: Bile leakage is a major complication after right lobe living donor liver transplantation (RLDLT). It can result in significant morbidities and, occasionally, mortalities. Endo-radiology is a non-surgical means that has been used to manage this complication. This study reviews the outcomes of the endo-radiological approach to the management of bile leakage after RLDLT with duct-to-duct anastomosis (DDA) at a high-volume center. METHOD: A retrospective study was conducted on all adult patients who received RLDLT at our center between January 2001 and December 2013. There were 496 RLDLTs performed during the study period. Only patients who had DDA as the only bile duct reconstruction method were included in the study. RESULTS: Twelve (3.7%) out of the 328 study subjects developed bile leakage after RLDLT. Six out of these 12 patients were successfully treated with the endo-radiological approach without the need for laparotomy. They had endoscopic retrograde cholangiography with stenting followed by percutaneous drainage of biloma. One of the 12 patients died from recurrence of hepatocellular carcinoma 37 months after transplantation. The remaining 11 patients are all alive. CONCLUSION: The endo-radiological approach should be the first-line management for bile leakage for selected patients with DDA as the bile duct reconstruction method.

Transplantation of a 2-year-old deceased-donor liver to a 61-year-old male recipient.

The suitable size of a graft is a key element in the success of liver transplantation. A small-for-size liver graft is very likely to sustain a significant degree of injury as a result of ischemia, preservation, reperfusion, and rejection. Usually, small-for-size grafts are a concern in living-donor liver transplantation rather than in deceased-donor liver transplantation. Here, we describe the successful transplantation of a liver from a 2-year-old deceased donor to a 61-year-old male recipient who suffered from liver failure related to hepatitis B. No report of successful deceased-donor liver transplantation with discrepancies between donor and recipient age and size to such an extent has been found in the literature. Despite unusually large discrepancies, with effort in minimizing the ischemic time, revised surgical techniques, and strong regenerative power of the "young" graft, the old patient's liver function gradually returned to normal. This again proves that the definition of a "suitable graft" evolves with time and experience.

Pilot study of high-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients wait-listed for liver transplantation.

The objective of this study was to investigate the outcomes of high-intensity focused ultrasound (HIFU) ablation as a bridging therapy for patients with hepatocellular carcinoma (HCC) who had been wait-listed for deceased donor liver transplantation (DDLT). Adult patients with unresectable and unablatable HCCs within the University of California San Francisco criteria who had been wait-listed for DDLT were screened for their suitability for HIFU ablation as a bridging therapy if they were not suitable for transarterial chemoembolization (TACE). Treatment outcomes for patients receiving HIFU ablation, TACE, and best medical treatment (BMT) were compared. Fifty-one patients were included in the analysis. Before the introduction of HIFU ablation, only 39.2% of the patients had received bridging therapy (TACE only, n = 20). With HIFU ablation in use, the rate increased dramatically to 80.4% (TACE + HIFU, n = 41). The overall dropout rate was 51% (n = 26). Patients in the BMT group had a significantly higher dropout rate (P = 0.03) and significantly poorer liver function as reflected by higher Model for End-Stage Liver Disease scores and higher Child-Pugh grading. Clinically relevant ascites was found in 5 patients in the HIFU group and 2 patients in the BMT group, but none was found in the TACE group (P = 0.01 and P = 0.03, respectively). The TACE and HIFU groups had comparable percentages of tumor necrosis in excised livers (P = 0.35), and both were significantly higher than that in the BMT group (P = 0.01 and P = 0.02, respectively). In conclusion, HIFU ablation was safe even for HCC patients with Child-Pugh C disease. Its adoption increased the percentage of patients receiving bridging therapy from 39.2% to 80.4%. A randomized controlled trial for further validation of its efficacy is warranted.