Alpha-Fetoprotein Response after First Transarterial Chemoembolization (TACE) and Complete Pathologic Response in Patients with Hepatocellular Cancer.

Transarterial chemoembolization (TACE) is used as a bridging treatment in liver transplant candidates with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the main tumor marker used for HCC surveillance. The aim of this study was to assess the potential of using the AFP change after the first TACE in the prediction of complete tumor necrosis. The study comprised 101 patients with HCC who underwent liver transplantation (LT) after TACE in the period between January 2011 and December 2020. The ΔAFP was defined as the difference between the AFP value before the first TACE and AFP either before the second TACE or the LT. The receiver operator characteristics (ROC) curves were used to identify an optimal cut-off value. Complete tumor necrosis was found in 26.1% (18 of 69) and 6.3% (2 of 32) of patients with an initial AFP level under and over 100 ng/mL, respectively (p = 0.020). The optimal cut-off value of ΔAFP for the prediction of complete necrosis was a decline of ≥10.2 ng/mL and ≥340.5 ng/mL in the corresponding subgroups. Complete tumor necrosis rates were: 62.5% (5 of 8) in patients with an initial AFP < 100 ng/mL and decline of ≥10.2 ng/mL; 21.3% (13 of 61) in patients with an initial AFP < 100 ng/mL and decline of <10.2 ng/mL; 16.7% (2 of 12) in patients with an initial AFP > 100 ng/mL and decline of ≥340.5 ng/mL; and null in 20 patients with an initial AFP > 100 ng/mL and decline of <340.5 ng/mL, respectively (p = 0.003). The simple scoring system, based on the initial AFP and AFP decline after the first treatment, distinguished between a high, intermediate and low probability of complete necrosis, with an area under the ROC curve of 0.699 (95% confidence intervals 0.577 to 0.821, p = 0.001). Combining the initial AFP with its change after the first treatment enables early identification of the efficacy of TACE.

Postoperative Supplemental Oxygen in Liver Transplantation (PSOLT) does not reduce the rate of infections: results of a randomized controlled trial.

BACKGROUND: Despite inconsistent evidence, international guidelines underline the importance of perioperative hyperoxygenation in prevention of postoperative infections. Further, data on safety and efficacy of this method in liver transplant setting are lacking. The aim was to evaluate efficacy and safety of postoperative hyperoxygenation in prophylaxis of infections after liver transplantation. METHODS: In this randomized controlled trial, patients undergoing liver transplantation were randomly assigned to either 28% or 80% fraction of inspired oxygen (FiO2) for 6 postoperative hours. Infections occurring during 30-day post-transplant period were the primary outcome measure. Secondary outcome measures included 90-day mortality, 90-day severe morbidity, 30-day pulmonary complications, durations of hospital and intensive care unit stay, and 5-day postoperative bilirubin concentration, alanine and aspartate transaminase activity, and international normalized ratio (INR) (clinicatrials.gov NCT02857855). RESULTS: A total of 193 patients were included and randomized to 28% (n = 99) and 80% (n = 94) FiO2. With similar patient, operative, and donor characteristics in both groups, infections occurred in 34.0% (32/94) of patients assigned to 80% FiO2 as compared to 23.2% (23/99) of patients assigned to 28% FiO2 (p = 0.112). Patients randomized to 80% FiO2 more frequently developed severe complications (p = 0.035), stayed longer in the intensive care unit (p = 0.033), and had higher bilirubin concentration over first 5 post-transplant days (p = 0.043). No significant differences were found regarding mortality, duration of hospital stay, pulmonary complications, and 5-day aspartate and alanine transaminase activity and INR. CONCLUSIONS: Postoperative hyperoxygenation should not be used for prophylaxis of infections after liver transplantation due to the lack of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02857855. Registered 7 July 2016.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Predictors of Long-Term Outcomes After Liver Transplantation Depending on the Length of Cold Ischemia Time.

BACKGROUND: Cold ischemia time (CIT) is one of the most significant variables affecting graft survival after liver transplantation. The aim of this study was to identify other predictors of worse graft survival depending on the duration of cold ischemia. METHODS: This retrospective cohort study included data of liver transplant recipients and donors in the period from 2014 to 2019. A total of 724 patients were analyzed after excluding retransplatations and urgent operations. Using receiver operating characteristic analysis, we identified CIT value which divides into 2 clinically different subgroups with respect to 5-year graft loss. Within those 2 subgroups, we performed Cox proportional hazard analysis with time to graft loss as endpoint. RESULTS: The optimal cut-off point for CIT was identified as 496 minutes. Model of end-stage liver disease score, recipient body mass index, and donor sodium concentration showed no significant effect on time to graft loss in either subgroup. For 3 factors we observed a significant effect on time to graft loss in subgroup CIT ≥496 min: transfused red cell concentrate units (hazard ratio [HR] 1.05; 95% confidence interval [CI] 1.00-1.09; P = .02), transfused fresh frozen plasma units (HR 1.04; 95% CI 1.00-1.08; P = .08), and a recipient age of >60 years (HR 1.81; 95% CI 1.10-2.98; P = .02). CONCLUSIONS: Predictive ability of well-known risk factors for worse outcomes after liver transplantation depend on the length of cold ischemia.

The Effect of Early Retransplantation on Early and Late Survival After Liver Transplantation.

BACKGROUND: Early liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival. METHODS: This retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival. RESULTS: The cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001). CONCLUSIONS: The early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.

Early Postoperative Transaminase Activities Affecting Early and Late Liver Graft Survival.

BACKGROUND: This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival. METHODS: This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss. RESULTS: The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P < .001 and 2.23; 95% CI 1.55-3.19; P < .001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was ≥1030 and ≥3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P < .001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P < .001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P = .924 and P = .629, respectively). CONCLUSIONS: Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.

The Utility of Early Allograft Dysfunction Components in Determining 90-Day Liver Graft Survival.

BACKGROUND: Early allograft dysfunction (EAD) had been established as a useful tool to asses graft and patient survival after liver transplant. We wanted to evaluate effect of EAD components on early graft survival. METHODS: This retrospective study included 264 patients with EAD after liver transplant in the period between 2015 and 2019. The patients with retransplants were excluded from analyses. The EAD was determined with Olthoff criteria. The logistic regression model was used for analyses. The 90-day graft survival was set as a primary outcome measure. RESULTS: The main indications for transplant in the analyzed group were hepatitis C virus infection (53 patients, 20.1%), hepatitis B infection (22, 8.3%), primary sclerosing cholangitis (28, 10.1%), and alcoholic liver disease (62, 23.5%), with a median model for end-stage liver disease score of 13.5 points. The 90-day graft loss occurred in 51 patients (19.3%). Each of the components used in EAD diagnosis was found to be correlated with 90-day graft loss. The bilirubin concentration on day 7 (odds ratio [OR], 3.1; 95% CI, 1.4-6.7; P < .001), international normalized ratio on day 7 (OR, 179; 95% CI, 39-815; P < .001), and the natural logarithm of alanine aminotransferase (OR, 3.1; 95% CI, 1.6-6.4) and aspartate aminotransferase (OR, 1.4; 95% CI, 0.4-4.9) predicted 90-day graft loss. CONCLUSIONS: In patients with EAD, international normalized ratio ≥ 1.6 on day 7 was the strongest predictor of early graft-loss among all EAD components.

Early results of the implementation of laparoscopic major liver resection program.

BACKGROUND: Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent. METHODS: This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay. RESULTS: Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) (p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) (p = 0.031). CONCLUSIONS: Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.

Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions: First Results of a Randomized Controlled Trial.

OBJECTIVE: To compare the early results of mass and layered closure of upper abdominal transverse incisions. SUMMARY OF BACKGROUND DATA: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. METHODS: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). RESULTS: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. CONCLUSIONS: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.

Applicability of common inflammatory markers in diagnosing infections in early period after liver transplantation in intensive care setting.

Infections remain an important cause of morbidity and mortality early after liver transplantation. The aim of this prospective longitudinal study was to evaluate clinical utility of c-reactive protein (CRP), procalcitonin, and neutrophil-to-lymphocyte ratio (NLR) in surveillance of infections early after liver transplantation in intensive care setting. A total of 60 liver transplant recipients were included. CRP, procalcitonin, and NLR assessed at 12-hour intervals were primary variables of interest. Infections and severe complications during postoperative intensive care unit stay were the primary and secondary end-points, respectively. Infections and severe complications were diagnosed in 9 and 17 patients, respectively. Only peak CRP beyond first 48 hours was associated with infections (p = 0.038) with AUC, positive and negative predictive value of 0.728, 42.9% and 92.2%, respectively (cut-off: 142.7 mg/L). Peak procalcitonin over first 60 hours was the earliest predictor (p = 0.050) of severe complications with AUC, positive and negative predictive value of 0.640, 53.3% and 80.0%, respectively (cut-off: 42.8 ng/mL). In conclusion, while CRP, procalcitonin, and NLR cannot be used for accurate diagnosis of infections immediately after liver transplantation, peak CRP beyond 48 hours and peak procalcitonin over first 60 hours may be used for initial exclusion of infections and prediction of severe complications, respectively.

A Comparison of Intrathecal and Intravenous Morphine for Analgesia After Hepatectomy: A Randomized Controlled Trial.

BACKGROUND: Effective analgesia is essential for patient recovery after liver resection. This study aimed to evaluate the effects of the addition of preoperative intrathecal morphine to multimodal intravenous analgesia in patients undergoing liver resection. METHODS: In this single-blind randomized controlled trial, patients undergoing liver resection were randomly assigned to the patient-controlled analgesia with (ITM-IV) or without (IV) preoperative intrathecal morphine groups. All patients received acetaminophen and dexketoprofen. The primary outcome was pain severity at rest over three postoperative days, assessed using the numerical rating scale (NRS). RESULTS: The study included 36 patients (18 in each group). The mean maximum daily NRS scores over the first three postoperative days in the ITM-IV and IV groups were 1.3, 1.1, and 0.3 and 1.6, 1.1, and 0.7, respectively (p = 0.580). No differences were observed in pain severity while coughing, with corresponding scores of 2.8, 2.1, and 1.1, respectively, in the ITM-IV group and 2.3, 2.2, and 1.5, respectively, in the IV group (p = 0.963). Proportions of patients reporting clinically significant pain at rest and while coughing were 11.1% and 44.4%, respectively, in the ITM-IV group, and 16.7% and 44.4%, respectively, in the IV group (both p > 0.999). Cumulative morphine doses in the ITM-IV and IV groups were 26 mg and 17 mg, respectively (p = 0.257). Both groups also showed similar time to mobilization (p = 0.791) and solid food intake (p = 0.743), sedation grade (p = 0.584), and morbidity (p = 0.402). CONCLUSIONS: Preoperative intrathecal morphine administration provides no benefits to multimodal analgesia in patients undergoing liver resection. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov Identifier: NCT03620916.

Fulminant liver failure following a marathon: Five case reports and review of literature.

BACKGROUND: The growing popularity of marathon and half-marathon runs has led to an increased number of patients presenting with exertion-induced heat stroke. Mild hepatic involvement is often observed in these patients; however, fulminant liver failure may occur in approximately 5% of all cases. Liver transplantation is a potentially curative approach for exertion-induced liver failure, although there is a lack of consensus regarding the criteria and optimal timing of this intervention. CASE SUMMARY: This paper describes 5 patients (4 men and 1 woman) who were referred to the department where this study was performed with the diagnosis of exertion-induced acute liver failure. Three patients underwent liver transplantation, 1 recovered spontaneously, and 1 patient died on day 11 following the exertion. CONCLUSION: Exertion-induced heat stroke may present as fulminant liver failure. These patients may recover with conservative treatment, may require liver transplantation, or may die. No definitive criteria are available to determine patient suitability for a conservative vs surgical approach.

Successful Hepatoatrial Anastomosis During a Consecutive Liver Retransplant in the Same Patient Shows Good Long-Term Results: Case Report and 2-Year Follow-Up.

Liver retransplant is the last and only treatment for patients with irreversible graft failure. It is recognized as a high-risk procedure; thus surgical difficulties are multiplied with every successive liver transplant. Liver retransplant is a demanding technical procedure for the surgeon, with no guarantee of postoperative and long-term survival. Here, we report a 29-year-old male patient who underwent a liver transplant in April 2009 due to primary sclerosing cholangitis with overlapping autoimmune hepatitis. The patient underwent liver retransplant in May 2012 due to graft failure. A second liver retransplant was performed in April 2013 using the classical technique. An inflammatory process involving the inferior vena cava and diaphragm forced the surgeon to open the pericardium from the diaphragm and clamp the cuff of the right atrium to perform a hepatoatrial anastomosis of the inferior vena cava. The next steps were performed as for a typical liver transplant. Postoperative stay was free of complications and was not prolonged. Immunosuppression regimen was kept standard. During our follow-up of more than 32 months, the patient continued to show good results. A consecutive hepatectomy in the same recipient is associated with an increased risk of intraoperative complications. When excessive adhesions limit a safe and functioning cavocaval anastomosis, a hepatectomy with the excision of the intrahepatic inferior vena cava and end-to-end anastomosis through a pericardial window for the extension of the recipient's' vena cava cuff are feasible options. We found that a hepatoatrial anastomosis does not impair good overall outcomes and long-term results.

Reoperations for Intraabdominal Bleeding Following Deceased Donor Liver Transplantation.

UNLABELLED: Intraabdominal hemorrhage remains one of the most frequent surgical complications after liver transplantation. The aim of the study was to evaluate risk factors for intraabdominal bleeding requiring reoperation and to assess the relevance of the reoperations with respect to short- and long-term outcomes following liver transplantation. MATERIAL AND METHODS: Data of 603 liver transplantations performed in the Department of General, Transplant and Liver Surgery in the period between January 2011 and September 2014 were analyzed retrospectively. Study end-points comprised: reoperation due to bleeding and death during the first 90 postoperative days and between 90 postoperative day and third post-transplant year. RESULTS: Reoperations for intraabdominal bleeding were performed after 45 out of 603 (7.5%) transplantations. Low pre-transplant hemoglobin was the only independent predictor of reoperation (p=0.002) with the cut-off of 11.3 g/dl. Postoperative 90-day mortality was significantly higher in patients undergoing reoperation as compared to the remaining patients (15.6% vs 5.6%, p=0.008). Post-transplant survival from 90 days to 3 years was non-significantly lower in patients after reoperation for bleeding (83.3%) as compared to the remaining patients (92.2%, p=0.096). Nevertheless, multivariable analyses did not reveal any significant negative impact of reoperations for bleeding on short-term mortality (p=0.589) and 3-year survival (p=0.079). CONCLUSIONS: Surgical interventions due to postoperative intraabdominal hemorrhage do not appear to affect short- and long-term outcomes following liver transplantation. Preoperative hemoglobin concentration over 11.3 g/dl is associated with decreased risk of this complication, yet the clinical relevance of this phenomenon is doubtful.