First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Allogeneic hematopoietic stem cell and liver transplantation in a young girl with dedicator of cytokinesis 8 protein deficiency.

DOCK8 deficiency is a rare inherited combined immunodeficiency, caused by mutations in the DOCK8 gene. We describe a case with DOCK8 deficiency associated with severe CLD in whom orthotopic LT was performed successfully after allogeneic HSCT. A 5 year-old girl with DOCK8 deficiency presented with mild direct hyperbilirubinemia and abnormal GGT level and without a previous history of jaundice. She had severe growth retardation, hepatosplenomegaly and generalized eczema. Progressive worsening of CLD was observed within 4 months. Investigations for etiology of liver disease were negative. Liver biopsy showed bridging necrosis, cholestasis and, cirrhosis. Recurrent immune hemolytic crisis and several viral infections developed in follow-up. She underwent whole cadaveric LT for end-stage liver disease (ESLD) 1 year after allogenic HSCT from a full matched related donor. The postoperative course was uneventful. The patient is alive with normal liver function and moderate skin graft versus host disease for 36 months after LT. In conclusion DOCK8 deficiency can be associated with severe CLD. Successful LT following HSCT is possible in patients with ESLD in DOCK8 deficiency. The timing of LT is challenging in patients requiring both HSCT and LT since conditioning regimens for HSCT can be highly hepatotoxic and the patients with suboptimal liver function can become decompensated during HSCT.

Assessing hepatic steatosis by magnetic resonance in potential living liver donors.

PURPOSE: To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings. METHODS: A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner. RESULTS: Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604-0.798, r = 0.654, 95% CI: 0.544-0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 (P < 0.001, 95% CI: 0.766-0.907) and 0.810 ± 0.036 (P < 0.001, 95% CI: 0.739-0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 (P < 0.001 95% CI: 0.804-0.937) and 0.855 ± 0.036 (P < 0.001, 95% CI: 0.784-0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively. CONCLUSION: The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy.

Management of Biliary Complications in Liver Transplant Recipients with Duct-To-Duct Anastomosis: A Single-Center Experience.

BACKGROUND: The aims of this study were to investigate biliary complications in liver transplant recipients with choledochocholedocho stomy anastomosis, to identify the risk factors for the development of such complications, and to evaluate the success of endoscopic approaches in liver transplant recipients. METHODS: Between January 2013 and May 2021, a total of 238 patients with liver diseases underwent liver transplantation: 174 recipients undergoing choledochocholedochostomy anastomosis were included in the analysis. RESULTS: Their median age was 54.0 years. The median posttransplant follow-up period was 29 months. Hepatitis B virus infection (33%) was the most common indication for liver transplantation. Most patients (87%) received living donor liver transplantation. The overall prevalence of posttransplant biliary complications was 31%. Anastomotic biliary strictures were the most common biliary complications (72%), followed by biliary leakage (13%). The median time between endoscopic retrograde cholangiography and liver transplantation was 4 months, with a mean of 3 ± 1.6 sessions. Endoscopic retrograde cholangiography-guided drainage and balloon dilation with or without stent placement was the most common treatment modalities for recipients with biliary strictures. The overall success rate of endoscopic treatment modalities was 83.3%, with 65% of the recipients exhibiting complete biochemical and endoscopic responses. The response did not differ significantly between living donor liver transplantation and cadaveric donor liver transplant recipients (P > .05). Three recipients required revision surgery for biliary complication repair. Six patients died due to biliary sepsis. CONCLUSION: Biliary stricture and leakages were the most common biliary complications after liver transplantation. Endoscopic treatment was successful in most recipients.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

Effect of Pretransplant Infections on Clinical Outcomes in Live-Donor Liver Transplant Recipients.

Owing to impaired immune function, surgical procedures, and multiple hospitalizations, patients with end-stage liver disease are at risk for numerous infectious complications while waiting for transplantation. Infection in transplant recipients remains the main cause of mortality and morbidity, despite advances in surgical techniques and the development of new repressive agents. The purpose of this study is to examine the infections that develop during the pretransplantion period in live donor liver transplant recipients and their effect on post-transplant clinical outcomes. The retrospective analysis of adult live donor liver transplant recipients in the last 4 years was conducted at Ankara University Hospital, a 1900-bed tertiary-care university hospital, in Ankara, Turkey. Demographic characteristics, preoperative infections, and clinical outcomes were analyzed. Patients were divided into 2 groups according to whether they had developed an infection before transplantation. The diagnoses were based on clinical, laboratory, and microbiological findings. Statistical analyses were performed using Stata version 9.0 (StataCorp, College Station, Tex., United States), and P < .05 were considered statistically significant. In univariate analyses, having diabetes mellitus or a pretransplant infection, the number of pretransplant infection attacks, the need for a reoperation, and developing a post-transplant infection were the statistically significant factors associated with 1-year mortality (P < .001, χ2 test). In multivariate analyses, diabetes mellitus (Odds ratio [OR] = 7.44, 95% confidence interval [CI], .03-45.79; P = .013), reoperation (OR = .33, 95% CI, .25-2.20; P < .001), having a pretransplantation infection (OR = 12.47, 95% CI, .011-87.67; P = .013), and the number of pretransplantation infection attacks (OR = .028, 95% CI, .013-.47; P < .001) were found to be statistically significant risk factors for 1-year mortality. Our study showed the effect of pretransplantation infections on post-transplant morbidity but not on rejection or mortality. According to the situation of patients, manageable pretransplantation infection is not an absolute contraindication for liver transplantation. Awareness of the increased risk for post-transplant infections and fast-acting antimicrobial coverage are the most important facts for patient survival.

Carbapenemase-Producing Bacterial Infections in Patients With Liver Transplant.

Carbapenemase-producing Enterobacteriacea (CPE) cause serious and life-threatening infections. They are resistant to carbapenems and many other classes of commonly used antimicrobial agents; therefore, managing infections caused by them poses a substantial challenge in clinical practice. They can also cause morbidity and mortality in patients with liver transplant. A retrospective analysis of CPE culture-positive patients with a history of liver transplant can help to examine the epidemiology and microbiology of these bacteria, as well as gain information on the possible infection sources, susceptibility patterns, and expected mortality in infected populations. In addition, study of these bacteria could help formulate a consensus on the appropriate use of empirical and directed antibiotic therapy, which can effectively reduce infections in these patients. We reviewed the medical records of 142 subjects who underwent liver transplantation at Ankara University Hospital, a 1900-bed tertiary care university hospital, in Ankara, Turkey, between January 2014 and August 2018. Patients showing signs of infection with culture positivity for CPE-producing organisms were included from the study. Statistical analysis was performed and a value of P < .05 is considered statistically significant. In most cases, the source of infection was the abdomen. Klebsiella species was also predominant in these cases. Model for End-Stage Liver Disease scores and length of hospital stay were higher and statistically significant when compared to patients who were CPE negative. Mortality was highest in the CPE-positive group. Infection is the most important cause of mortality and morbidity after liver transplantation and increases the cost of treatment. Regarding the culture sensitivity patterns and resistance mode, empirical therapy with carbapenems does not produce a solid result. The high mortality observed with these infections reflects very limited therapeutic options.