To perform a systematic review and meta-analysis on donor-to-recipient gender mismatch as a risk factor for post-transplant graft loss.
A systematic literature search was performed using PubMed, ...Cochrane Library database and EMBASE. The primary outcome was graft loss after liver transplantation. Odds ratios and 95% confidence intervals were calculated to compare the pooled data between groups with different donor-to-recipient gender matches. Three analyses were done considering (1) gender mismatches (F-M and M-F)
matches (M-M and F-F); (2) Female-to-Male mismatch
other matches; and (3) Male-to-Female mismatch
other matches.
A total of 7 articles were analysed. Gender mismatch (M-F and F-M) was associated with a significant increase of graft loss respect to match (M-M and F-F) (OR: 1.30; 95%CI: 1.13-1.50;
< 0.001). When F-M mismatch was specifically investigated, it confirmed its detrimental role in terms of graft survival (OR: 1.83; 95%CI: 1.20-2.80;
= 0.005). M-F mismatch failed to present a significant role (OR: 1.09; 95%CI: 0.73-1.62;
= 0.68).
Gender mismatch is a risk factor for poor graft survival after liver transplantation. Female-to-male mismatch represents the worst combination. More studies are needed with the intent to better clarify the reasons for these results.
Background
Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a new surgical technique for the resection of advanced hepatic malignancies with predicted ...insufficient future liver remnant. In some patients, ALPPS can be associated with an increased risk of poor outcomes. Minimally invasive surgery (MIS) has been proposed in combination with ALPPS with the intent to minimize this risk. We systematically evaluated the outcomes of MIS-ALPPS cases to compare the relative outcomes of open ALPPS versus MIS-ALPPS.
Methods
A systematic review was done in accordance with the PRISMA guidelines. Search terms utilized included the following: (“ALPPS”Title/Abstract OR “associating liver partition and portal vein ligation for staged hepatectomy”Title/Abstract OR “in situ split”Title/Abstract) AND (“minimally invasive”Title/Abstract OR “laparoscopic”Title/Abstract OR “robotic”Title/Abstract).
Results
Fifteen articles were identified, with a total of 27 patients reported. Colorectal metastatic disease was the most commonly observed indication for MIS-ALPPS (66.7%), followed by hepatocellular carcinoma (25.9%). Time passed from the first to the second stage ranged 7–30 days. MIS-ALPPS patients did not experience procedure failures between the first and second stages. Only four (15.4%) subjects had a grade IIIb complication. No perioperative mortality after the first or second stage was reported. Compared with open ALPPS, MIS-ALPPS demonstrated better results. Hospital stay duration ranged 8–33 days with a follow-up ranging 1–20 months.
Conclusions
MIS-ALPPS appears to be safe, with potentially lower morbidities and mortalities relative to open patients. The present results should be considered with caution. A limited number of articles exist on this topic. Furthermore, selection biases exist when comparing open versus MIS-ALPPS data. Registry studies are needed to better define the outcomes of patients undergoing MIS-ALPPS.
Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved ...outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out 25.2%) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre‐LT levels of alpha‐fetoprotein, Model for End‐Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest‐risk patients (HALTHCC 0‐5) had lower rates of VI and PDC than the highest‐risk patients (HALTHCC > 35) (VI, 7.7% 1.2‐14.2 vs. 70.6% 48.3‐92.9 and PDC:4.6% 0.1%‐9.8% vs. 47.1% 22.6‐71.5; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C‐index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C‐index = 0.71) and OS (C‐index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre‐LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.
Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for ...cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12–250 months). All cardiovascular events were carefully recorded and detailed in the patients’ charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60–6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36–7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.
Objectives
To prospectively compare the diagnostic performance of ultrasound (US), multidetector computed tomography (MDCT) and contrast-enhanced magnetic resonance imaging (MRI) in cirrhotic ...patients who were candidates for liver transplantation.
Methods
One hundred and forty consecutive patients with 163 hepatocellular carcinoma (HCC) nodules underwent US, MRI and MDCT. Diagnosis of HCC was based on pathological findings or substantial growth at 12-month follow-up. Four different image datasets were evaluated: US, MDCT, MRI unenhanced and dynamic phases, MRI unenhanced dynamic and hepatobiliary phase. Diagnostic accuracy, sensitivity, specificity, PPV and NPV, with corresponding 95 % confidence intervals, were determined. Statistical analysis was performed for all lesions and for three lesion subgroups (<1 cm, 1-2 cm, >2 cm).
Results
Significantly higher diagnostic accuracy, sensitivity and NPV was achieved on dynamic + hepatobiliary phase MRI compared with US, MDCT and dynamic phase MRI alone. The specificity and PPV of US was significantly lower than that of MDCT, dynamic phase MRI and dynamic + hepatobiliary phase MRI. Similar results were obtained for all sub-group analyses, with particular benefit for the diagnosis of smaller lesions between 1 and 2 cm.
Conclusions
Dynamic + hepatobiliary phase MRI improved detection and characterisation of HCC in cirrhotic patients. The greatest benefit is for diagnosing lesions between 1 and 2 cm.
Key Points
•
US, CT and MRI can all identify HCC in cirrhotic patients
•
US has good sensitivity but suffers from false-positive findings
•
Dynamic CT and MR have similar diagnostic performance for diagnosing HCC
•
Dynamic + hepatobiliary phase MRI significantly improves detection and characterisation of HCC
•
The greatest benefit is for the diagnosis of lesions between 1 and 2 cm
Sarcopenia is a frequent complication in liver transplant (LT) recipients. β-hydroxy-β-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating ...the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.
In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and ...doctor–patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing
en
bloc
the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.
In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) ...macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving ≥50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by α-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.
(1) Background: We investigated, for the first time, whether dietary simple sugar intake affects MELD score changes over time in a cohort of cirrhotic liver transplant candidates. (2) Methods: the ...MELD score, dietary habits using a 3-day food diary, and visceral adipose tissue index (VATI) measured with CT scan were assessed in 80 consecutive outpatient cirrhotic patients at baseline, after counseling to follow current nutritional guidelines. The MELD score was reassessed after six months and the DELTA-MELD was calculated as the MELD at the second assessment minus the MELD at baseline. (3) Results: Compared with the baseline, the MELD score of cirrhotic patients at the end of the study was decreased, stable, or increased in 36%, 8% and 56% of patients, respectively. In separate multiple linear regression models, DELTA-MELD was positively and independently correlated with the daily intake of simple sugars expressed in g/kg body weight (
= 0.01) or as a percentage of total caloric intake (
= 0.0004) and with the number of daily portions of fruit, added sugar, jam, and honey (
= 0.003). These associations were present almost exclusively in patients with VATI above the median value. (4) Conclusions: In cirrhotic patients with high amounts of visceral adipose tissue the consumption of simple sugars and fructose should be limited to improve their clinical outcome.
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