A Systematic Review and Meta-Analysis: Do We Still Need Microscope Surgery in Hepatic Artery Anastomosis to Decrease the Incidence of Complications in Living Donor Liver Transplantation?

Hepatic artery thrombosis (HAT) is the most serious vascular complication after liver transplantation (LT). Moreover, in comparison to deceased donor liver transplantation (DDLT), hepatic artery (HA) anastomosis is more challenging in living donor liver transplantation (LDLT) with a lot of controversial topics about the use of microscopic surgery. We aimed to compare the use of microscopic and loupe surgery in HA anastomosis in adult and pediatric LDLT to decrease the incidence of vascular complications. We searched PubMed, Scopes, Web of Science, and Cochrane Library for eligible studies from inception to April 2023 and a systematic review and a meta-analysis were done. According to our eligibility criteria, 10 studies with a total of 1939 patients were included. In comparison to microscopic surgery, loupe anastomosis has a similar incidence of HAT (thrombosis, risk ratio (RR) = 0.96, 95% CI = 0.26-3.48, P = 0.95). In addition to that, no significant difference was detected between the two types in terms of stenosis, decreased blood flow and hospital stay (decreased blood flow, RR = 0.68, 95% CI = 0.01-86.65, P = 0.88), (stenosis, RR = 1.81, 95% CI = 0.19-17.21, P = 0.60), (hospital stay, mean deviation (MD) = 1.16, 95% CI = -3.79-6.11, P = 0.65). However, the anastomotic time was longer in the case of microscopic surgery (anastomotic time, MD = 24.09, 95% CI = 7.79-40.39, P = 0.004). With an equal incidence of complications and longer anastomotic time, there is no added benefit of the routine use of microscopic surgery in HA anastomosis in LDLT.

Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region.

Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.

Central hepatectomy versus major hepatectomy for patients with centrally located hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: For those with a centrally located HCC, the two types of liver sectionectomy that can be performed are extended hepatectomy (EH) and central hepatectomy (CH). This meta-analysis aimed to compare the short- and long-term outcomes between patients treated with CH and patients treated with EH for those with centrally located HCC. METHOD: We searched PubMed, Scopus, Web of Science, and Cochrane library for eligible studies from inception to 1 April 2022 and a systematic review and meta-analysis were done to compare the outcomes between the two groups. RESULTS: we included 9 studies with a total of 1674 patients in this study. The pooled results in this meta-analysis showed equal long-term overall survival, Disease-free survival, recurrence and mortality between the two groups (5-year OS, RR = 1.14, 95% CI = 0.96-1.35, P = 0.12; I2 = 56%), (5-year DFS, RR = 0.81, 95% CI = 0.61-1.08, P = 0.15; I2 = 60%), (Recurrence, RR = 1.04, 95% CI = 0.94-1.15, P = 0.45; I2 = 27%), and (Mortality, RR = 0.55, 95% CI = 0.26-1.15, P = 0.11; I2 = 0%). In addition to that, no significant difference could be detected in the overall incidence of complications between the two groups (Complications, RR = 0.94, 95% CI = 0.76-1.16, P = 0.57; I2 = 0%). However, CH is associated with a remarkable increase in the rate of biliary fistula (Biliary fistula, RR = 1.90, 95% CI = 1.07-3.40, P = 0.03; I2 = 0%). And Liver cell failure was higher in the case of EH (LCF, RR = 0.47, 95% CI = 0.30-0.76, P = 0.002; I2 = 0%). Regarding the operative details, CH is associated with longer operative time (Time of the operation, Mean difference = 0.82, 95% CI = 0.36, 1.27, P = 0.0004; I2 = 57%). CONCLUSION: No significant difference in the short and long-term survival and recurrence between CH and MH for CL-HCC. However, CH is associated with greater future remnant liver volume that decreases the incidence of LCF and provides more opportunities for a repeat hepatectomy after tumour recurrence.

Can living donor liver transplantation provide similar outcomes to deceased-donor liver transplantation for hepatocellular carcinoma? A systematic review and meta-analysis.

BACKGROUND AND AIM: A potential solution to the deceased organ shortage is to include live organ donations and to identify patients with lower rates of HCC recurrence to fairly allocate liver grafts. Our aims were to detect the long-term outcomes of LDLT versus DDLT for HCC and predictors of recurrence after transplantation. METHODS: PubMed, Scopus, Web of Science, Cochrane library were searched for eligible studies from inception to July 2021 and a systematic review and meta-analysis were done. RESULTS: 35 studies with a total of 7822 patients were included. The 1-, 3-, 4 year-OS showed trivial improvement for LDLT recipients. However, the two modalities had similar 5-, 6- and 10-year OS. A significant improvement in the ITT-OS was observed for LDLT recipients. Regarding the DFS and recurrence after transplantation, no significant difference was observed between LDLT and DDLT. In addition to that, the pooled hazard ratio of the included studies showed that Milan criteria, level of AFP, presence of vascular invasion, tumor differentiation were significant predictors of recurrence. CONCLUSION: The cancer biology (not the graft type) is the most important determinant of recurrence and survival after LT. However, LDLT provided much better survival benefits to HCC patients especially in regions that suffer from low deceased organ availability.

Do We Need to Use a Stent in Biliary Reconstruction to Decrease the Incidence of Biliary Complications in Liver Transplantation? A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Biliary complications are a significant cause of morbidity post-transplantation, and the routine use of biliary stents in liver transplantation to reduce these complications remains controversial. This study aimed to compare the incidence of biliary complications with and without the use of trans anastomotic biliary stent in liver transplantation. METHOD: PubMed, Scopes, Web of Science, and Cochrane library were searched for eligible studies from inception to February 2022, and a systematic review and meta-analysis were done to compare the incidence of biliary complications in the two groups. RESULTS: Seventeen studies with a total of 2623 patients were included. The pooled results from the included studies showed an equal rate of biliary complications (i.e., strictures, leaks and cholangitis) in stented and non-stented patients after liver transplantation. However, the cost and biliary intervention rates are higher in stented patients. In addition to that, our sub-group analysis showed no significant decrease in the incidence of biliary complications after using trans anastomotic biliary stent in living donor liver transplant (LDLT), deceased donor liver transplant (DDLT), Roux-en-Y hepaticojejunostomy (RYHJ), and duct-to-duct anastomosis, pediatric, and adult liver transplantation. CONCLUSION: No added benefit on the routine use of endobiliary stent in liver transplantation. However, stented patients are at higher risk of needing multiple ERCPs.

Validation of electrical velocimetry in resuscitation of patients undergoing liver transplantation. Observational study.

Major hemodynamic changes are frequently noted during liver transplantation (LT). We evaluated the performance of electrical velocimetry (EV) as compared to that of TEE in SV optimization during liver transplantation. This was an observational study in 32 patients undergoing LT. We compared SV values measured simultaneously by EV (SVEV) and TEE (SVTEE) at baseline 30 min after induction, at the end of dissection phase, 30 min after anhepatic phase, 30 min after reperfusion. We also evaluated the reliability of EV to track changes In SV before and after 49 fluid challenges. Finally, the SV variation (SVV) and pulse pressure variation (PPV) were tested as predictors for volume responsiveness, defined as an increase in SV ≥ 10% after 250 ml of colloid. For 112 paired SV data, the overall correlation was 0.76 and bias (limits of agreement) 0.3 (- 29 to 29) ml percentage error 62%. The EV was able to track changes in SV with a concordance rate of 97%, and a sensitivity and specificity of 93% to detect a positive fluid challenge. The AUC values (with 95% confidence intervals) for SVV and PPV were 0.68 (0.52-0.83) and 0.72 (0.57-0.86), respectively, indicating low predictive capacity in these setting. The absolute values of SV derived from EV did not agree with SV derived from TEE. However, EV was able to track the direction of changes in SV during hemodynamic management of patients undergoing liver transplantation.Clinical trial registration: Clinicaltrials.gov Identifier: NCT03228329 prospectively Registered on 13-July-2017.

Evaluation of the diagnostic and therapeutic roles of non-coding RNA and cell proliferation related gene association in hepatocellular carcinoma.

Micro RNA-34a-5p (miR-34a-5p) is an important molecule that can act as a modulator of tumor growth. It controls expression of a plenty of proteins controlling cell cycle, differentiation and apoptosis and opposing processes that favor viability of cancer cells, their metastasis and resistance to chemotherapy. Bioinformatics analysis indicated that minichromosome maintenance protein 2 (MCM2) is a target gene of miR-34a-p. In this study, RT-qPCR was employed to detect the expression of miR-34a-5p and MCM2 in 10 hepatocellular carcinoma (HCC) tissues. The functional role of miR-34a-5p in HCC was investigated and the interaction between miR-34a-5p and MCM2 was explored. Results showed miR-34a-5p expression in HCC tissues was significantly lower than in non HCC liver tissues (P < 0.05), but MCM2 expression in HCC tissues was markedly higher than in non HCC liver tissues (P < 0.05). In addition, miR-34a-5p expression was negatively related to MCM2 expression. To confirm effect of miR-34a-5p on tumor growth and its possible effect on MCM2, miR-34a-5p mimic and inhibitor was transfected into HCC cell lines (HepG2). MTS assay, showed miR-34a-5p over-expression could inhibit the proliferation of HCC cells. RT-qPCR was done to detect the expression of miR-34a-5p and MCM2 in HepG2 cells before and after transfection. Results showed that MCM2 expression in HCC tissues was markedly lower in mimic transfected group than in inhibitor transfected group and control group (P < 0.05) while miR-34a-5p expression in HepG2 cells was significantly higher in mimic transfected group than in inhibitor transfected group and control group (P < 0.05). Thus, miR-34a-5p may inhibit the proliferation of HCC cells via regulating MCM2 expression. These findings provide an evidence for the emerging role of microRNAs as diagnostic markers and therapeutic targets in HCC.

Effects of bacterial translocation on hemodynamic and coagulation parameters during living-donor liver transplant.

BACKGROUND: Bacterial translocation (BT) has been proposed as a trigger for stimulation of the immune system with consequent hemodynamic alteration in patients with liver cirrhosis. However, no information is available regarding its hemodynamic and coagulation consequences during liver transplantation. METHODS: We screened 30 consecutive adult patients undergoing living-donor liver transplant for the presence of BT. Bacterial DNA, Anti factor Xa (aFXa), thromboelastometry, tumor necrosis factor-α TNF-α, and interleukin-17 (IL-17) values were measured in sera before induction of anesthesia. Systemic hemodynamic data were recorded throughout the procedures. RESULTS: Bacterial DNA was detected in 10 patients (33%) (bactDNA(+)). Demographic, clinical, and hemodynamic data were similar in patients with presence or absence of bacterial DNA. BactDNA(+) patients showed significantly higher circulating values of TNF-α and IL-17, and had significantly higher clotting times and clot formation times as well as significantly lower alpha angle and maximal clot firmness than bactDNA(-) patients, P < 0.05. We found no statistically significant difference in aFXa between the groups, P = 0.4. Additionally, 4 patients in each group needed vasopressor agents, P = 0.2. And, the amount of transfused blood and blood products used were similar between both groups. CONCLUSION: Bacterial translocation was found in one-third of patients at the time of transplantation and was largely associated with increased markers of inflammation along with decreased activity of coagulation factors. TRIAL REGISTRATION: Trial Registration Number: NCT03230214 . (Retrospective registered). Initial registration date was 20/7/2017.

Immunohistochemical and electron microscopic morphometric image analysis of hepatocellular carcinoma in association of HCV infection.

Early detection of hepatocellular carcinoma (HCC) is crucial for successful therapy. The present work examined the value of ultrastructural morphometric image analysis of hepatocyte nuclei in patients with chronic hepatitis C virus (HCV) versus HCC cases with chronic HCV and the corresponding surgical tumor-free safe margins (TFMs), to highlight any early predictive signs of neoplastic cellular transformation. This work also performed an immunohistochemical assessment of cytokeratin 19 (CK19) and Ki-67-positive cells to visualize any associated proliferative activity in the examined groups. The results showed significant decrease in the hepatocyte nuclear surface areas in the HCC and TFMs versus those in the HCV cases. The hepatocyte nucleolar surface area was significantly increased in the HCC cases versus that in the HCV cases. This increase was associated with a significant increase in Ki-67-positive cells in the HCC cases compared to those in the other groups. Conversely, the mean number of CK 19-positive cells was significantly reduced in the HCC cases compared to the cell numbers in TFMs and HCV cases with severe hepatic fibrosis. Liver progenitor cells (LPCs) were discerned in the reactive ductules and canaliculo-ductular junctions that characterized TFMs. LPCs were sporadically distributed in the liver lobules and reactive bile ductules in the HCC samples. In conclusion, CK 19 represents an important marker for distinguishing between dysplastic and malignant liver nodules. Electron microscopic morphometric image analysis may be considered as adjunct factor for assessing hepatocyte malignant transformation. Wider scale studies are needed to authenticate these results.

Potential ultrastructure predicting factors for hepatocellular carcinoma in HCV infected patients.

Hepatitis C virus represents one of the rising causes of hepatocellular carcinoma (HCC). Although the early diagnosis of HCC is vital for successful curative treatment, the majority of lesions are diagnosed in an irredeemable phase. This work deals with a comparative ultrastructural study of experimentally gradually induced HCC, surgically resected HCC, and potential premalignant lesions from HCV-infected patients, with the prospect to detect cellular criteria denoting premalignant transformation. Among the main detected pathological changes which are postulated to precede frank HCC: failure of normal hepatocyte regeneration with star shape clonal fragmentation, frequent elucidation of hepatic progenitor cells and Hering canals, hepatocytes of different electron density loaded with small sized rounded monotonous mitochondria, increase junctional complexes bordering bile canaliculi and in between hepatocyte membranes, abundant cellular proteinaceous material with hypertrophied or vesiculated rough endoplasmic reticulum (RER), sequestrated nucleus with proteinaceous granular material or hypertrophied RER, formation of lipolysosomes, large autophagosomes, and micro-vesicular fat deposition. In conclusion, the present work has visualized new hepatocytic division or regenerative process that mimic splitting or clonal fragmentation that occurs in primitive creature. Also, new observations that may be of value or assist in predicting HCC and identifying the appropriate patient for surveillance have been reported. Moreover, it has pointed to the possible malignant potentiality of liver stem/progenitor cells. For reliability, the results can be subjected to cohort longitudinal study.

The use of terlipressin during living donor liver transplantation: Effects on systemic and splanchnic hemodynamics and renal function.

OBJECTIVES: To assess the effect of the intraoperative use of terlipressin on splanchnic hemodynamics and postoperative renal function in patients undergoing liver transplantation. DESIGN: Open-label, prospective, randomized study. SETTING: Single-center study. PATIENTS: Thirty patients who underwent elective, living-donor liver transplantation with portal pressure >20 mm Hg. INTERVENTIONS: Patients were assigned randomly to one of two equal groups. The control group received saline, whereas the treatment group (TP group) received an initial bolus dose of terlipressin (1 mg over 30 mins) followed immediately by a continuous infusion of 2 µg·kg(-1)·h(-1) for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Portal pressure and gas exchange (radial artery, portal vein, and hepatic vein, blood gas analyses, and lactate concentration) were assessed at baseline (after ligation of the hepatic artery) and 2 hrs after drug administration. Systemic hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Renal function was assessed by measurement of serum cystatin C after induction of anesthesia and on the first 2 days postoperatively. After the infusion of terlipressin, portal venous pressure decreased significantly from 26.3 ± 3.3 to 21.3 ± 3.6 mm Hg (p < .001). The mean arterial pressure and systemic vascular resistance were significantly higher in the TP group than in the control group, whereas heart rate and cardiac index were comparable between the groups. Portal and hepatic base excess, and the level of serum lactate, did not differ between the two groups. The serum levels of both cystatin C and creatinine were significantly higher in the control group than in the TP group on postoperative day 2. CONCLUSION: Perioperative use of terlipressin abrogates the early postoperative decline in renal function of patients who have chronic liver disease and undergo liver transplantation without any detrimental effect on hepatosplanchnic gas exchange and lactate metabolism.