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Objective: 

The aim of this study was to assess the impact of having a living donor on waitlist outcomes and overall survival through an intention-to-treat analysis.

Background: 

Living-donor liver transplantation (LDLT) offers an alternative to deceased donation in the face of organ shortage. An as-treated analysis revealed that undergoing LDLT, compared with staying on the waiting list, is associated with improved survival, even at Model for End-stage Liver Disease-sodium (MELD-Na) score of 11.

Methods: 

Liver transplant candidates listed at the Ajmera Transplant Centre (2000–2021) were categorized as pLDLT (having a potential living donor) or pDDLT (without a living donor). Employing Cox proportional-hazard regression with time-dependent covariates, we evaluated pLDLT’s impact on waitlist dropout and overall survival through a risk-adjusted analysis.

Results: 

Of 4124 candidates, 984 (24%) had potential living donors. The pLDLT group experienced significantly lower overall waitlist dropouts (5.2% vs 34.4%, P<0.001) and mortality (3.8% vs 24.4%, P<0.001) compared with the pDDLT group. Possessing a living donor correlated with a 26% decline in the risk of waitlist dropout (adjusted hazard ratio=0.74, 95% CI: 0.55–0.99, P=0.042). The pLDLT group also demonstrated superior survival outcomes at 1 year (84.9% vs 80.1%), 5 years (77.6% vs 61.7%), and 10 years (65.6% vs 52.9%) from listing (log-rank P<0.001) with a 35% reduced risk of death (adjusted hazard ratio=0.65, 95% CI: 0.56–0.76, P<0.001). Moreover, the predicted hazard ratios consistently remained <1 across the MELD-Na range of 11 to 26.

Conclusions: 

Having a potential living donor significantly improves survival in end-stage liver disease patients, even with MELD-Na scores as low as 11. This emphasizes the need to promote awareness and adoption of LDLT in liver transplant programs worldwide.

Background

Solitary hepatocellular carcinoma measuring ≤3 cm represents approximately 30% of hepatocellular carcinoma cases, yet treatment guidelines lack robust evidence. This study compares oncologic outcomes after ablation, liver resection, and liver transplantation for solitary, small hepatocellular carcinoma.

Methods

We systematically searched databases up to 7 February 2022, for studies including adults with solitary hepatocellular carcinoma ≤3 cm treated by any ablation, liver resection, or liver transplantation. We excluded non-hepatocellular carcinoma cancers, recurrent/metastatic diseases, and alternative therapies. A frequentist network meta-analysis assessed 5-year overall survival and recurrence-free survival using only adjusted effect estimates while accounting for bias risk.

Results

We identified 80 studies (4 randomized controlled trials, 72 retrospectives, and 4 prospective cohorts) with 28,211 patients. In the network meta-analysis for 5-year overall survival (26 studies), liver transplantation was associated with the lowest mortality hazard (hazard ratio, 0.47; 95% confidence interval, 0.31–0.73, referenced to liver resection), followed by liver resection (reference), whereas ablation had the greatest mortality hazard (hazard ratio, 1.32; 95% confidence interval, 1.16–1.49, referenced to liver resection). For 5-year recurrence-free survival (19 studies), liver transplantation had the best outcome (hazard ratio, 0.36; 95% confidence interval, 0.20–0.63, referenced to liver transplantation), followed by liver resection (reference), with ablation showing the least favorable outcome (hazard ratio, 1.67; 95% confidence interval, 1.45–1.93, referenced to liver resection).

Conclusions

This network meta-analysis provides the evidence for comparing treatment modality outcomes for solitary, small (≤3 cm) hepatocellular carcinoma. LT emerges as the superior choice for achieving a better 5-year OS, followed by liver resection, then ablation. When feasible to preserve liver function, liver resection can be prioritized. Ablation with close surveillance should be reserved for individuals unfit for surgery.

Background

The impact of treatment on hepatitis C virus with direct-acting antivirals on 90-day postoperative outcomes, overall survival, and recurrence-free survival in patients after liver resection for hepatocellular carcinoma is unknown.

Methods

We conducted a multicenter retrospective study. Adults who underwent liver resection for hepatitis C virus–related hepatocellular carcinoma between January 2000 and December 2018 were included from 7 international institutions. Groups included direct-acting antiviral treated, non–direct-acting antiviral treated, and untreated hepatitis C virus infection. We used a multivariable model to evaluate the association between receipt of preoperative direct-acting antivirals and 90-day postoperative major complications (Clavien-Dindo class ≥III).

Results

We identified 738 patients, including 206 (28%) direct-acting antiviral treated, 241 (33%) non–direct-acting antiviral treated, and 291 (39%) untreated patients. The sustained virologic response rate was 92% in the direct-acting antiviral and 71% in the non–direct-acting antiviral treatment groups. The median follow-up was 7.6 years (95% confidence interval 6.1, 8.6) after surgery for the entire cohort. Patients who received direct-acting antiviral therapy had better 5-year overall and recurrence-free survival than those without antiviral therapy (adjusted hazard ratio [95% confidence interval]: 0.26 [0.19, 0.35] and 0.52 [0.43, 0.64], respectively). Patients who received direct-acting antiviral therapy had better 5-year overall and recurrence-free survival than those who received non–direct-acting antiviral therapy (adjusted hazard ratio [95% confidence interval]: 0.49 [0.36, 0.66] and 0.78 [0.63, 0.96], respectively). There was no significant association between preoperative direct-acting antiviral therapy and 90-day postoperative major complications (adjusted odds ratio 0.34, 95% confidence interval 0.08, 1.01).

Conclusion

Direct-acting antiviral therapy is associated with improved 5-year overall and recurrence-free survival, without significantly increased risk of 90-day postoperative complications, in patients undergoing liver resection for hepatitis C virus–related hepatocellular carcinoma.

Background and Aims: 

Liver transplant (LT) for transplant oncology (TO) indications is being slowly adopted worldwide and has been recommended to be incorporated cautiously due to concerns about mid-long-term survival and its impact on the waiting list.

Approach and Results: 

We conducted 4 systematic reviews of all series on TO indications (intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma [phCC]) and liver metastases from neuroendocrine tumors (NETs) and colorectal cancer (CRLM) and compared them using patient-level meta-analyses to data obtained from the United Network for Organ Sharing (UNOS) database considering conventional daily-practice indications. Secondary analyses were done for specific selection criteria (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan criteria for NET). A total of 112,014 LT were analyzed from 2005 to 2020 from the UNOS databases and compared with 345, 721, 494, and 103 patients obtained from meta-analyses on intrahepatic cholangiocarcinoma and phCC, and liver metastases from NET and CRLM, respectively. Five-year overall survival was 53.3%, 56.4%, 68.6%, and 53.8%, respectively. In Mantel-Cox one-to-one comparisons, survival of TO indications was superior to combined LT, second, and third LT and not statistically significantly different from LT in recipients >70 years and high BMI.

Conclusions: 

Liver transplantation for TO indications has adequate 5-year survival rates, mostly when performed under the selection criteria available in the literature (Mayo-like protocols for phCC, SECA-2 for CRLM, and Milan for NET). Despite concerns about its impact on the waiting list, some other LT indications are being performed with lower survival rates. These oncological patients should be given the opportunity to have a definitive curative therapy within validated criteria.

Background.Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the Western world. Although 6 mo of abstinence is no longer a criterion for patients with ALD, the outcomes of living donor LT (LDLT) versus deceased donor LT (DDLT) are not well established.Methodss.We performed an intention-to-treat analysis to evaluate the impact of listing and pursuing primary LDLT (pLDLT) compared with primary DDLT (pDDLT). The primary endpoint was overall survival from date of listing, evaluated using Cox regression (hazard ratios).Results.Two hundred thirty-three patients with ALD were listed for LT, of which 27 (12%) were pLDLT. The overall median model for end-stage liver disease (MELD) score at listing was 20 and Na-MELD 24, a median abstinence of 4.5 mo, and 128 (55%) underwent transplantation. There was no statistically significant adjusted difference at 3-y overall survival between pLDLT versus pDDLT (adjusted hazard ratio [HR] 0.72; P = 0.550) and in the as-treated analysis (HR 1.22; P = 0.741). No patients were delisted in the pLDLT group, whereas 86 (42%) patients were delisted in the pDDLT group; primarily because of death (46 [50%]) and medical improvement (24 [28%]). Alcohol use since the time of listing was documented in 29 (13%) patients; immortal time bias adjusted analysis found no significant difference between pLDLT and pDDLT (adjusted HR 1.07; P = 0.900) and the as-treated analysis (HR 2.95; P = 0.130).Conclusions.Patients with ALD benefit from intention pLDLT with lower rates of waitlist dropout and delisting, attributable to mortality or medical deterioration, and should be encouraged to pursue this option.

Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquar tile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m2 (IQR: 23.2-30.0 kg/m2), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.

Objective:To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score.Background:LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC).Methods:Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method.Results:Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% (P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% (P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%.Conclusions:Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [p<0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [p<0.05]). There were no differences in the 1-, 3, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p=0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [p>0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Background & Aims: Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres.

Methods: A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents' contemporary decision making process, a hypothetical case study with different tumour size and number combinations was embedded.

Results: Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise.

Conclusions: Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA.

Impact and implications: Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeon vs. oncologist vs. hepatologist/ gastroenterologist), highlighting the urgent need for a standardisation of therapeutic strategies for patients with cHCC-CCA.