Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

Antiplatelet agent for the prevention of late hepatic vascular complications in living donor liver transplant dominant population.

BACKGROUND: Evidence for the long-term use of antiplatelet drugs to prevent hepatic vascular complications (HVC) is scarce in liver transplantation (LT). METHODS: From national claim data, LT recipients (about 80 % of living donor LT [LDLT]) without graft loss, HVC, or cardiovascular events within 1 year, were classified into those who took antiplatelets for ≥1 year (n = 1744) and for <1 year (n = 1975). Outcomes were compared after the 1-postoperative year index time point. RESULTS: During a mean follow up of 4.5 years, the risk of graft loss was similar between the groups (aHR 1.16, P = 0.23). However, ≥1-year antiplatelet therapy was associated with a higher risk of graft loss after 3 years (aHR 2.19, P < 0.01). HVC (aHR 0.94, P = 0.87) and major adverse cardiac events (aHR 1.20, P = 0.46) did not correlate with antiplatelet therapy for both groups. In contrast, ≥1-year antiplatelet therapy showed a significantly higher risk of severe bleeding compared to <1-year antiplatelet therapy (aHR 2.24, P < 0.01). This trend was similar in the LDLT subgroup. In our cohort, antiplatelet therapy for ≥1 year did not improve graft survival or HVC; however, it increased the risk of severe bleeding. CONCLUSION: We recommend against antiplatelet therapy for more than 1 year in clinically stable LT recipients.

Clinical Impact and Risk Factors of Seizure After Liver Transplantation: A Nested Case-Control Study.

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23 kg/m2, donor age ≥45 years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome.

Anticoagulation in patients with end-stage kidney disease and atrial fibrillation: a national population-based study.

Background: The prevalence of atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) is high and increasing. However, evidence regarding oral anticoagulant (OAC) use in these patients is insufficient and conflicting. Methods: This retrospective cohort study included patients in the Korea National Health Insurance System diagnosed with AF after ESKD onset from January 2007 to December 2017. The primary outcome was all-cause death. Secondary outcomes were ischaemic stroke, hospitalization for major bleeding and major adverse cardiovascular events (MACE). Outcomes were compared between OAC users and non-users using 6-month landmark analysis and 1:3 propensity score matching (PSM). Results: Among patients with ESKD and AF, the number of prescribed OACs increased 2.3-fold from 2012 (n = 3579) to 2018 (n = 8341) and the proportion of direct OACs prescribed increased steadily from 0% in 2012 to 51.4% in 2018. After PSM, OAC users had a lower risk of all-cause death {hazard ratio [HR] 0.67 [95% confidence interval (CI) 0.55-0.81]}, ischaemic stroke [HR 0.61 (95% CI 0.41-0.89)] and MACE [HR 0.70 (95% CI 0.55-0.90)] and no increased risk of hospitalization for major bleeding [HR 0.99 (95% CI 0.72-1.35)] compared with non-users. Unlike warfarin, direct OACs were associated with a reduced risk of all-cause death and hospitalization for major bleeding. Conclusions: In patients with ESKD and AF, OACs were associated with reduced all-cause death, ischaemic stroke and MACE.

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients.

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.

Kidney Transplantation From Brain-Dead Donors With Hepatitis B or C in South Korea: A 2015 to 2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND: According to the current Center for Korean Network for Organ Sharing guidelines for kidney transplantation from brain-dead donors with hepatitis B or C infection, organs from hepatitis B surface antigen-positive (HbsAg+) or anti-hepatitis C virus-positive (HCV+) donors can only be transplanted into HBsAg+ or anti-HCV+ recipients. We aimed to confirm the status and the outcomes of kidney transplantation from brain-dead donors with hepatitis B or C virus in Korea. METHODS: This retrospective study included all kidney transplantations from brain-dead donors in the Korean Organ Transplantation Registry database between January 2015 and June 2020, divided into 3 groups according to donor hepatitis status. Finally, kidney transplantations from 80 HBV+, 12 HCV+, and 2013 HBV-/HCV- donors were included. RESULTS: No statistically significant differences were observed in the recipient characteristics and the transplant outcomes except the waiting time (HBV+ to HBV-/HCV-, P < .001; HCV+ to HBV-/HCV-, P = .10; HBV+ to HCV+P = .95). Five-year graft survival rates of the HBV+, HCV+, and HBV-/HCV- recipients were 95%, 83%, and 85%, respectively (HBV+ to HCV+, P = .22; HCV+ to HBV-/HCV-, P = .81; HBV+ to HBV-/HCV-, P = .02). Five-year patient survival rates of the HBV+, HCV+, and HBV-/HCV- recipients were 95%, 100%, and 76%, respectively (HBV+ to HCV+, P = .61; HCV+ to HBV-/HCV-, P = .13; HBV+ to HBV-/HCV-, P < .001). CONCLUSION: HBV+/HCV+ brain-dead donor kidney transplantation outcomes were comparable to HBV-/HCV-. South Korea should consider conditionally permitting transplantation from HBV+ or HCV+ donors to HBV- or HCV- recipients to accumulate new data and conduct further studies.

High Number of Plasma Exchanges Increases the Risk of Bacterial Infection in ABO-incompatible Living Donor Liver Transplantation.

BACKGROUND: Bacterial infections are major complications that cause significant mortality and morbidity in living donor liver transplantation (LDLT). The risk of bacterial infection has not been studied in ABO-incompatible (ABOi) recipients with a desensitization protocol in relation to the number of plasma exchanges (PEs). Therefore, we aimed to analyze the risk of bacterial infection in ABOi LDLT recipients with a high number of PEs compared with recipients with a low number of PEs. METHODS: A retrospective study was performed with 681 adult LDLT recipients, of whom 171 ABOi LDLT recipients were categorized into the high (n = 52) or low (n = 119) PE groups based on a cutoff value of 6 PE sessions. We compared bacterial infections and postoperative bacteremia within 6 mo after liver transplantation with the ABO-compatible (ABOc) LDLT group (n = 510) as a control group. RESULTS: The high PE group showed a bacterial infection rate of 49.9% and a postoperative bacteremia rate of 28.8%, which were significantly higher than those of the low PE group (31.1%, 17.8%) and the ABOc group (26.7%, 18.0%). In multivariate analysis, the high PE group was found to have a 2.4-fold higher risk of bacterial infection (P = 0.008). This group presented a lower 5-y survival rate of 58.6% compared with the other 2 groups (81.5% and 78.5%; P = 0.030 and 0.001). CONCLUSIONS: A high number of preoperative PEs increases bacterial infection rate and postoperative bacteremia in ABOi LDLT.

Cumulative exposure to tacrolimus during early period after liver transplantation does not affect the recurrence of hepatocellular carcinoma.

The clinical effects of tacrolimus (TAC) exposure on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remain unclear. In this retrospective single centric study, 512 patients who underwent LT for HCC were divided into four groups according to cumulative exposure to tacrolimus (CET) during 3 months after LT: conventional (n = 218), aggressive minimization (n = 32), minimization (n = 161), and high exposure (n = 101). Impact of CET on HCC recurrence and death were analyzed. Compared with the conventional group, the other three CET groups showed a similar risk of HCC recurrence. The aggressive minimization group showed a higher risk [hazard ratio (HR) 5.64, P < 0.001] and the high exposure group showed a marginal risk (HR 1.67, P = 0.081) of overall death compared to the conventional group. CET during 3 months was not associated with HCC recurrence in the matched cohort and various subgroups. TAC minimization is not effective to prevent HCC recurrence but could result in higher mortality in LT recipients.

One-way donor-to-recipient human leukocyte antigen mismatch and graft-versus-host disease in liver transplantation: an observational study of a single-center experience in Korea.

Background: Graft-versus-host disease (GVHD) is a rare, but potentially fatal complication of liver transplantation. One-way human leukocyte antigens (HLA) mismatch has emerged as a risk factor for GVHD. However, the risk of mortality associated with HLA-one-way mismatch (OWMM) remains uncertain. We investigated the incidence and characteristics of GVHD. Methods: In total, 899 patients who underwent liver transplantation at a single center were retrospectively reviewed. The incidence of GVHD and 1- and 5-year survival rates were compared according to whether HLA-OWMM developed. Results: In the HLA-OWMM group, GVHD developed in two patients (14.3%). Notably, GVHD was only observed in living donor liver transplant (LDLT) recipients in the HLA-OWMM group. The HLA-OWMM group exhibited a lower 1-year patient survival rate than the control (i.e., non-HLA-OWMM) group (78.6% vs. 90.7%, P=0.120). However, the 5-year survival rate in the HLA-OWMM group was similar to that in the control group (78.6% vs. 78.2%, P=0.821). When the HLA-OWMM group was further stratified by the number of mismatched loci, the 5-year survival rate was 83.3% in patients with HLA-OWMM at one to two loci and 75.0% in those with HLA-OWMM at three loci. Conclusions: Despite the higher incidence of GVHD in LDLT recipients with HLA-OWMM, the 5-year patient survival rates were comparable to those in recipients without HLA-OWMM. The decision to perform LDLT in patients with HLA-OWMM depends on the patient's status and the organ supply of a specific region.

The Effect of Model for End-Stage Liver Disease 3.0 on Disparities between Patients with and without Hepatocellular Carcinoma in Korea.

PURPOSE: The model for end-stage liver disease (MELD) 3.0 has recently been suggested for determining liver allocation. We aimed to apply MELD 3.0 to a Korean population and to discover differences between patients with and without hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study is a retrospective study of 2203 patients diagnosed with liver cirrhosis at Severance Hospital between 2016-2022. Harrell's concordance index was used to validate the ability of MELD scores to predict 90-day survival. RESULTS: During a mean follow-up of 12.9 months, 90-day survival was 61.9% in all patients, 50.4% in the HCC patients, and 74.8% in the non-HCC patients. Within the HCC patients, the concordance index for patients on the waitlist was 0.653 using MELD, which increased to 0.753 using MELD 3.0. Among waitlisted patients, the 90-day survival of HCC patients was worse than that of non-HCC patients with MELD scores of 31-37 only (69.7% vs. 30.0%, p=0.001). Applying MELD 3.0, the 90-day survival of HCC patients was worse than that of non-HCC patients across a wider range of MELD 3.0 scores, compared to MELD, with MELD 3.0 scores of 21-30 and 31-37 (82.0% vs. 72.5% and 72.3% vs. 24.3%, p=0.02 and p<0.001, respectively). CONCLUSION: MELD 3.0 predicted 90-day survival of the HCC patients more accurately than original MELD score; however, the disparity between HCC and non-HCC patients increased, particularly in patients with MELD scores of 21-30. Therefore, a novel exception score is needed or the current exception score system should be modified.

Clinical significance of the living kidney donor profile index for predicting long-term posttransplant outcomes: results from the Korean Organ Transplantation Registry.

Background: The usefulness of the living kidney donor profile index (LKDPI) has not been widely demonstrated; therefore, it requires verification before clinical application. We analyzed the LKDPI using data from the Korean Organ Transplantation Registry (KOTRY) to confirm whether the LKDPI can be used to predict the survival of allografts in living donor kidney transplantation (LDKT) patients in Korea. Methods: The study population was obtained from the KOTRY database. A total of 2,598 kidney recipients registered in the KOTRY database were enrolled between May 2014 and December 2020. Donor and recipient information was observed, and the LKDPI was measured. Results: Median LKDPI score was 15.5 with a follow-up duration of 33.7 ± 16.1 months. According to LKDPI scores (group 1, <0; group 2, 0-20; group 3, 20-40; and group 4, >40), LKDPI group 4 had significantly higher death-censored graft loss than LKDPI group 1 (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.06- 3.40; p = 0.03). When divided based on the cutoff value (LKDPI, 36.6), the high LKDPI group had higher graft loss than the low LKDPI group (HR, 2.14; 95% CI, 1.37-3.34; p < 0.001). When follow-up was repeated after transplantation, it was confirmed that the higher the LKDPI value was, the lower the average estimated glomerular filtration rate (p < 0.001). Conclusion: This study confirmed that LKDPI can serve as an independent predictor for assessing the risk of allograft failure and transplant outcomes in Korean LDKT patients.

Unusual grafts for living-donor liver transplantation.

PURPOSE: Unusual grafts, including extended left liver plus caudate lobe, right anterior section, and right posterior section grafts, are alternatives to left and right lobe grafts for living-donor liver transplantation. This study aimed to investigate unusual grafts from the perspectives of recipients and donors. METHODS: From 2016 to 2021, 497 patients received living-donor liver transplantation at Severance Hospital. Among them, 10 patients received unusual grafts. Three patients received extended left liver plus caudate lobe grafts, two patients received right anterior section grafts, and five patients received right posterior section grafts. Liver volumetrics and anatomy were analyzed for all recipients and donors. We collected data on laboratory examinations (alanine aminotransferase, total bilirubin, international normalized ratio), imaging studies, graft survival, and complications. A 1:2 ratio propensity-score matching method was used to reduce selection bias and balance variables between the unusual and conventional graft groups. RESULTS: The median of Model for End-stage Liver Disease score of unusual graft recipients was 13.5 (interquartile range 11.5-19.3) and that of graft-recipient weight ratio was 0.767 (0.7-0.9). ABO incompatibility was observed in four cases. The alanine aminotransferase level, total bilirubin level, and international normalized ratio decreased in both recipients and donors. Unusual and conventional grafts had similar survival rates (p = 0.492). The right and left subgroups did not differ from each counter-conventional subgroup (p = 0.339 and p = 0.695, respectively). The incidence of major complications was not significantly different between unusual and conventional graft recipients (p = 0.513). Wound seromas were reported by unusual graft donors; the complication ratio was similar to that in conventional graft donors (p = 0.169). CONCLUSION: Although unusual grafts require a complex indication, they may show feasible surgical outcomes for recipients with an acceptable donor complication.

Outcomes and Risk Factors for Liver Transplantation Using graft-to-Recipient Weight Ratio Less than 0.8 Graft from Living Donors: Multicentric Cohort Study.

OBJECTIVE: To compare graft survival after LDLT in patients receiving GRWR<0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts. SUMMARY BACKGROUND DATA: Favorable outcomes after living donor liver transplantation (LDLT) using graft-to-recipient weight ratio (GRWR)<0.8 grafts were recently reported; however, these results have not been validated using multicenter data. METHODS: This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score-matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors. RESULTS: In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-y graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs. 90.1%, P=0.013). Adjusted hazard ratio (HR) for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% confidence interval [CI] 1.17-2.35, P=0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 y, MELD score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed higher risk of graft loss compared to GRWR≥0.8 graft in LDLT (HR 2.98, 95% CI 1.79-4.88, P<0.001). CONCLUSIONS: GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs. 90.1%), especially when ≥2 risk factors for graft loss (among age ≥60 y, MELD score ≥15, or male donor) were present.

Survival Benefit of Kidney Transplantation in Patients With End-Stage Kidney Disease and Prior Acute Myocardial Infarction.

Patients with end stage kidney disease (ESKD) and a previous acute myocardial infarction (AMI) have less access to KT. Data on ESKD patients with an AMI history who underwent first KT or dialysis between January 2007 and December 2018 were extracted from the Korean National Health Insurance Service. Patients who underwent KT (n = 423) were chronologically matched in a 1:3 ratio with those maintained on dialysis (n = 1,269) at the corresponding dates, based on time-conditional propensity scores. The 1, 5, and 10 years cumulative incidences for all-cause mortality were 12.6%, 39.1%, and 60.1% in the dialysis group and 3.1%, 7.2%, and 14.5% in the KT group. Adjusted hazard ratios (HRs) of KT versus dialysis were 0.17 (95% confidence interval [CI], 0.12-0.24; p < 0.001) for mortality and 0.38 (95% CI, 0.23-0.51; p < 0.001) for major adverse cardiovascular events (MACE). Of the MACE components, KT was most protective against cardiovascular death (HR, 0.23; 95% CI, 0.12-0.42; p < 0.001). Protective effects of KT for all-cause mortality and MACE were consistent across various subgroups, including patients at higher risk (e.g., age >65 years, recent AMI [<6 months], congestive heart failure). KT is associated with lower all-cause mortality and MACE than maintenance dialysis patients with a prior AMI.

Predicted Impact of the Model for End-Stage Liver Disease 3.0 in a Region Suffering Severe Organ Shortage.

BACKGROUND: The model for end-stage liver disease 3.0 (MELD3.0) is expected to address the flaws of the current allocation system for deceased donor liver transplantation (DDLT). We aimed to validate MELD3.0 in the Korean population where living donor liver transplantation is predominant due to organ shortages. METHODS: Korean large-volume single-centric waitlist data were merged with the Korean Network for Organ Sharing (KONOS) data. The 90-day mortality was compared between MELD and MELD3.0 using the C-index in 2,353 eligible patients registered for liver transplantation. Patient numbers and outcomes were compared based on changes in KONOS-MELD categorization using MELD3.0. Possible gains in MELD points and reduced waitlist mortality were analyzed. RESULTS: MELD3.0 performed better than MELD (C-index 0.893 for MELD3.0 vs. 0.889 for MELD). When stratified according to the KONOS-MELD categories, 15.9% of the total patients and 35.2% of the deceased patients were up-categorized using MELD3.0 versus MELD categories. The mean gain of MELD points was higher in women (2.6 ± 2.1) than men (2.1 ± 1.9, P < 0.001), and higher in patients with severe ascites (3.3 ± 1.8) than in controls (1.9 ± 1.8, P < 0.001); however, this trend was not significant when the MELD score was higher than 30. When the possible increase in DDLT chance was calculated via up-categorizing using MELD3.0, reducible waitlist mortality was 2.7%. CONCLUSION: MELD3.0 could predict better waitlist mortality than MELD; however, the merit for women and patients with severe ascites is uncertain, and reduced waitlist mortality from implementing MELD3.0 is limited in regions suffering from organ shortage, as in Korea.

Survival benefit of living-donor liver transplantation in patients with a model for end-stage liver disease over 30 in a region with severe organ shortage: a retrospective cohort study.

BACKGROUND: The benefits of living-donor liver transplantation (LDLT) in patients with a high Model for End-stage Liver Disease (MELD) score (who have high waitlist mortality) are unclear. Regional availability of deceased-donor organs must be considered when evaluating LDLT benefits. The authors aimed to compare the survival benefit of intended-LDLT to awaiting deceased-donor liver transplantation (DDLT) in patients with a MELD score greater than or equal to 30 in a region with severe organ shortage. MATERIALS AND METHODS: This retrospective review included 649 patients with a MELD score greater than or equal to 30 placed on the liver transplantation waitlist. They were divided into intended-LDLT ( n =205) or waiting-DDLT ( n =444) groups based on living-donor eligibility and compared for patient survival from the time of waitlisting. Post-transplantation outcomes of transplant recipients and living donors were analyzed. RESULTS: Intended-LDLT patients had higher 1-year survival than waiting-DDLT patients (53.7 vs. 28.8%, P <0.001). LDLT was independently associated with lower mortality [hazard ratio (HR), 0.62; 95% CI, 0.48-0.79; P <0.001]. During follow-up, 25 patients were de-listed, 120 underwent LDLT, 170 underwent DDLT, and 334 remained on the waitlist. Among patients undergoing transplantation, the risk of post-transplantation mortality was similar for LDLT and DDLT after adjusting for pretransplantation MELD score (HR, 1.86; 95% CI, 0.73-4.75; P =0.193), despite increased surgical complications after LDLT (33.1 vs. 19.4%, P =0.013). There was no mortality among living-donors, but 4.2% experienced complications of grade 3 or higher. CONCLUSIONS: Compared to awaiting DDLT, LDLT offers survival benefits for patients with a MELD score greater than or equal to 30, while maintaining acceptable donor outcomes. LDLT is a feasible treatment for patients with a MELD score greater than or equal to 30 in regions with severe organ shortages.

Entecavir versus tenofovir on the recurrence of hepatitis B-related HCC after liver transplantation: A multicenter observational study.

Considerable controversy exists regarding the superiority of tenofovir disoproxil fumarate (TDF) over entecavir (ETV) for reducing the risk of HCC. This study aimed to compare outcomes of ETV versus TDF after liver transplantation (LT) in patients with HBV-related HCC. We performed a multicenter observational study using data from the Korean Organ Transplantation Registry. A total of 845 patients who underwent LT for HBV-related HCC were divided into 2 groups according to oral nucleos(t)ide analogue used for HBV prophylaxis post-LT: ETV group (n = 393) and TDF group (n = 452). HCC recurrence and overall death were compared in naïve and propensity score (PS)-weighted populations, and the likelihood of these outcomes according to the use of ETV or TDF were analyzed with various Cox models. At 1, 3, and 5 years, the ETV and TDF groups had similar HCC recurrence-free survival (90.7%, 85.6%, and 84.1% vs. 90.9%, 84.6%, and 84.2%, respectively, p = 0.98) and overall survival (98.4%, 94.7%, and 93.5% vs. 99.3%, 95.8%, and 94.9%, respectively, p = 0.48). The propensity score-weighted population showed similar results. In Cox models involving covariates adjustment, propensity score-weighting, competing risk regression, and time-dependent covariates adjustment, both groups showed a similar risk of HCC recurrence and overall death. In subgroup analyses stratified according to HCC burden (Milan criteria, Up-to-7 criteria, French alpha-fetoprotein risk score), pretransplantation locoregional therapy, and salvage LT, neither ETV nor TDF was superior. In conclusion, ETV and TDF showed mutual noninferiority for HCC outcomes when used for HBV prophylaxis after LT.

Effect of statins on the recurrence of hepatocellular carcinoma after liver transplantation: An illusion revealed by exposure density sampling.

BACKGROUND: Statins have been reported to reduce overall death and hepatocellular carcinoma (HCC) recurrence in liver transplantation (LT) recipients. However, previous retrospective studies have significant flaws in immortal time bias. METHODS: Using data from 658 patients who received LT for HCC, we matched 140 statin users with statin nonusers in a 1:2 ratio at the time of the first statin administration after LT using the exposure density sampling (EDS). The propensity score, calculated using baseline variables (including explant pathology), was used for EDS to equilibrate both groups. HCC recurrence and overall death were compared after adjusting for information at the time of sampling. RESULTS: Among statin users, the median time to statin start was 219 (IQR 98-570) days, and intensity of statins was mainly moderate (87.1%). Statin users and nonusers sampled using EDS showed well-balanced baseline characteristics, including detailed tumour pathology, and similar HCC recurrence with cumulative incidences of 11.3% and 11.8% at 5 years, respectively (p = .861). In multivariate Cox models (HR 1.04, p = .918) and subgroup analyses, statins did not affect HCC recurrence. Conversely, statin users showed a significantly lower risk of overall death than nonusers (HR 0.28, p < .001). There was no difference in the type and intensity of statin usage between statin users who experienced HCC recurrence and those who did not. CONCLUSION: Upon controlling immortal time bias by EDS, statins did not affect HCC recurrence but reduced mortality after LT. Statin usage is encouraged for survival benefits but not for preventing HCC recurrence in LT recipients.