Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community.

Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management.

BACKGROUND: NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. OBJECTIVE: To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor® on this network. METHODS: First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-ß, were estimated by ELISA. RESULTS: Mutaflor® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-ß effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. CONCLUSION: Mutaflor® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.

Does pre-operative counselling of the donor improve immediate and short-term outcomes after living liver donation? - A review of the literature and expert panel recommendations.

BACKGROUND: There is some evidence in the literature to suggest that pre-operative counselling improves pain scores postoperatively. However, it is unclear whether pre-operative counselling of the donor improves immediate and short-term outcomes after living liver donation. OBJECTIVES: This systematic review aimed to investigate the available quality of evidence (QOE) of pre-operative counselling for living donors on short term outcomes, provide expert opinion, grade recommendations and identify relevant components for Enhanced Recovery after Surgery (ERAS) protocols. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Endpoints were defined by the WHOQOL-BREF scale: physical health, psychological, social relationships, and environment. PROSPERO ID: CRD42021260677. RESULTS: Screening of 452 records and full texts led to 12 articles matching inclusion criteria, of which one was a randomized controlled trial (RCT), and 11 were observational retrospective cohort studies. A total of 933 individuals undergoing donor hepatectomy were included, of whom only 90 received dedicated perioperative ERAS protocols. Donors that received pre-operative counselling had fewer physical symptoms post donation, lower rates of fatigue, lower rates of pain, shorter recovery times and fewer unexpected medical problems, and less anxiety post donation. Female donors had higher affective and adverse effects scores, and 50% of donors reported adverse effects to analgesia that interfered with functional activity. Receiving information about analgesic options increased perception of care among donors. CONCLUSIONS: Providing comprehensive pre-operative counselling to living liver donors is associated with improved short-term outcomes after donation (QOE; moderate to low I Grade of Recommendation; Strong).

De novo hepatocellular carcinoma in cirrhotic hepatitis C virus: Are directly acting antivirals beneficial?

BACKGROUND AND AIM: Behavior of HCC that developed after DAAs therapy for HCV infection is still debated. In this study we aim to compare characteristics and pattern of de novo HCC in cirrhotic HCV patients who were treated and untreated with DAAs. PATIENTS AND METHODS: This study included 160 cirrhotic HCV patients presented with de novo HCC during the period of December 2017 to December 2018. Patients were divided into two groups, group A included 80 patients who received DAAs and group B included 80 patients who were not exposed to DAAs. The characteristics of HCC in both groups were compared using BCLC Staging System. RESULTS: The size of the largest lesion was 47mm±26 in group A and 41mm±27 in group B with statistically significant difference between both groups (p=0.03). No other significant differences existed regarding number, site, or total tumor size and most of the lesions were solid in both groups. Portal vein thrombosis and extrahepatic spread detected in 16 and 11 patients in group A, while in group B the number was 17 and 9 patients respectively (p=0.83 and 0.06). No significant differences between groups in type of intervention done, BCLC staging (p=0.4), or survival. CONCLUSION: Although CHCV patients treated with DAAs had larger de novo HCC lesions than untreated patients, there was no difference in BCLC staging or in aggressive behavior between both groups.

Effect of Ramadan fasting on Muslim recipients after living donor liver transplantation: A single center study.

BACKGROUND AND STUDY AIMS: Several factors affect the quality of life and personal well-being of transplant recipients, including Ramadan fasting for Muslims. This study aimed to assess the effect of Ramadan fasting on the renal and liver functions of liver transplantation recipients and to propose a protocol for adapting an Immunosuppression regimen and follow-up schedule for patients wishing to fast after liver transplantation. PATIENTS AND METHODS: This prospective study was conducted on 45 recipients who wished to fast Ramadan from 17th May to 14th June 2018, at Ain Shams Center for Organ Transplantation, Cairo, Egypt. RESULTS: The mean age of the patients was 55.5 ± 7.2 (37-68) years, and 84.4% were males; the mean time from liver transplantation was 51.6 ± 28 months (14-117). Thirty-seven patients (82.2%) completed Ramadan fasting, three patients (6.6%) had interrupted fasting, and five patients (11.1%) had to stop fasting because of an unacceptable rise in renal function. There was a statistically significant difference between the pre- and post-fasting states in terms of the serum creatinine level (p = 0.004).However, the serum creatinine did not exceed the upper normal value in the patients who completed fasting. CONCLUSION: Our data seem promising for Ramadan fasting with an adapted immunosuppression protocol and regular follow-up for recipients wishing to fast. Further multicentre studies on a larger number of patients are warranted.

Outcome of Colonoscopic Screening in Potential Liver Transplant Candidates.

BACKGROUND: Screening for neoplastic lesions is mandatory as a part of the evaluation process of potential candidates for liver transplant (LT). This work aimed at identifying the main findings in screening colonoscopy and their risk factors. METHODS: Endoscopic and pathologic findings of the biopsied lesions of 311 potential candidates for living donor liver transplant were collected and analyzed. RESULTS: Colorectal polyps (8.7%) were the most common colonoscopic finding, of which 4.18% were diagnosed as adenomas. Other findings included hemorrhoids (7.7%), portal hypertensive colopathies (3.5%), angiomatous malformations (2.6%), rectal varices (1.6%), and diverticulosis (1.6%). The univariate analysis revealed that the prevalence of colonic adenoma was significant in patients 50 years and older (P = .03; odds ratio, 1.178; 95% CI, 1.016-1.365) and in patients who had hepatocellular carcinoma (P = .043; odds ratio, 6.5; 95% CI, 1.002-42.172). In the multivariate analysis, age was found to be the single best predictor of the presence of adenoma (P = .044; odds ratio, 1.178; 95% CI, 1.005-1.382). CONCLUSION: We can conclude that a screening colonoscopy prior to liver donor liver transplant should be performed at least in every LT candidate 50 years or older. Colonic polyps were the most common findings on screening colonoscopy prior to LT.

Efficacy of contrast-enhanced FDG PET/CT in patients awaiting liver transplantation with rising alpha-fetoprotein after bridge therapy of hepatocellular carcinoma.

OBJECTIVE: To assess the diagnostic accuracy and illustrate positive findings of contrast-enhanced fluorine-18 fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) image in patients awaiting liver transplantation (LT) with rising alpha-fetoprotein (AFP) after bridge therapy of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study included 100 patients who were waiting for LT and who previously underwent locoregional therapy (LRT) of HCC. These patients had rising AFP levels on a routine follow-up examination awaiting LT. All patients underwent a contrast-enhanced 18F-FDG PET/CT examination. We calculated for each patient the maximum standardised uptake value (SUVmax) of the tumour and the ratio of the tumoral SUVmax to the normal-liver SUVmax. The diagnostic accuracy and positive contrast-enhanced findings of 18F-FDG PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. RESULTS: Contrast-enhanced 18F-FDG PET/CT detected tumour relapse in 78 patients (13 patients had intrahepatic lesions, 10 patients had extrahepatic metastases and 55 patients with combined lesions). The sensitivity, specificity and accuracy values of contrast-enhanced 18F-FDG PET/CT examination in the detection of HCC recurrence were 92.8%, 94.1% and 93%, respectively. A significant correlation was found between the AFP level and SUVmax ratio (r = 0.2283; p = 0.0224). The best threshold for 18F-FDG PET positivity was >1.21. CONCLUSION: Contrast-enhanced 18F-FDG PET/CT is a valuable tool for the detection of intrahepatic HCC recurrence or extrahepatic metastasis following rising AFP levels after LRT of HCC, and should be incorporated during routine workup awaiting LT. KEY POINTS: • 18F-FDG PET/CT is a valuable tool for the detection of HCC recurrence • 18 F-FDG PET/CT should be incorporated during routine workup awaiting liver transplantation • Significant correlation was found between AFP level and SUVmax ratio • The best threshold for 18 F-FDG PET positivity was >1.21 • The ideal cut-off value for AFP was >202.

Efficacy of loco-regional treatment for hepatocellular carcinoma prior to living donor liver transplantation: a report from a single center in Egypt.

BACKGROUND AND AIM: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade, bridging or downstaging patients on the waiting list for liver transplantation. This study aimed to analyze the outcomes of LRTs prior to living donor liver transplantation in patients with HCC. METHODS: Sixty-two HCC patients received living donor liver transplantation at Ain Shams Center for Organ Transplantation over a 2-year period. Data from 29 HCC patients were analyzed. Twenty patients (68.97%) met the Milan Criteria and 4 patients (13.8%) exceeded the Milan Criteria, but met the University of California, San Francisco Criteria. Five patients (17.2%) exceeded the University of California, San Francisco Criteria. All patients underwent preoperative LRTs. The protocol of bridging/downstaging, methods, duration of follow-up, the number of patients who were successfully downstaged before liver transplantation (LT), and their outcomes after LT were recorded. RESULTS: There was a decrease in the mean overall size of focal lesions (from mean 5.46 to 4.11 cm) in the last abdominal computed tomography (CT) scan after LRT (p=0.0018). Discrepancies between the radiological findings and histopathology were as follows: in 16 patients (55.17%) the CT findings were consistent with the histopathological examination of the explanted liver. Underestimated tumor stage was documented in 10 patients (34.48%), and was overestimated by CT scan findings in 3 patients (10.34%). The 1-year survival rate was 93%. No patient had HCC recurrence after median follow-up of 21 months (range 1-46 months). CONCLUSION: These results encouraged tumor bridging/downstaging as a potential treatment option among carefully selected patients with HCC beyond conventional criteria for LT. Further studies on a large number of patients are necessary.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A single-center study.

AIM: To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation (LDLT) in cirrhotic patients. METHODS: This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra- and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS: Thirty-three patients (73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection (28.6% and 27.8%, respectively). The most common isolated organisms were gram-negative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes (19% and 33.3%, respectively), followed by Escherichia coli for repeated infections (11.1%), and Pseudomonas aeruginosa for single infections (19%). Levofloxacin showed high sensitivity against repeated infection episodes (P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant (MDR). Pre-transplant hepatocellular carcinoma (HCC) and duration of drain insertion (in days) were independent risk factors for the occurrence of repeated infection episodes (P = 0.024). CONCLUSION: MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

Annexin A2 as a biomarker for hepatocellular carcinoma in Egyptian patients.

AIM: To investigate the clinical utility of serum annexin A2 (ANXA2) as a diagnostic marker for early hepatocellular carcinoma (HCC). METHODS: This study was performed in HCC Clinic of Ain Shams University Hospitals, Cairo, Egypt and included: Group 1: Fifty patients with early stage HCC (Barcelona Clinic Liver Cancer stage A); Group 2: Twenty five patients with chronic liver disease; and Control Group: Fifteen healthy, age- and sex-matched subjects who were seronegative for viral hepatitis markers. The following laboratory investigations were done: Viral hepatitis markers [hepatitis B surface antigen and hepatitis C virus (HCV) antibodies], HCV RNA in HCV antibody-positive patients, serum alpha fetoprotein (AFP), and serum ANXA2 levels. RESULTS: In this study, 88% of HCC patients (n = 44) were HCV-positive, while HBV infection represented only 8% of all HCC patients (n = 4); and two patients were negative for both viral markers. A highly significant difference was found between patients with HCC and chronic liver disease as well as controls with regard to serum ANXA2 levels (130, IQR 15-240; 15, IQR 15-17; and 17, IQR 15-30 ng/mL, respectively). The area under the curve of ANXA2 was 0.865; the cut-off value was established to be 18 ng/mL with a diagnostic sensitivity of 74% and a specificity of 88%, while the sensitivity and specificity of AFP at the cut-off value of 200 ng/dL were 20% and 100%, respectively. CONCLUSION: Serum ANXA2 may serve as a biomarker for the early detection of HCC.

Safety, Efficacy, and Tolerability of Sofosbuvir and Ribavirin in Management of Recurrent Hepatitis C Virus Genotype 4 After Living Donor Liver Transplant in Egypt: What Have We Learned so far?

BACKGROUND: Recurrence of HCV after living donor liver transplant (LDLT) is nearly universal, with almost one third of recipients developing cirrhosis and graft failure within 5 years after LDLT. Different studies have been published on the effect of sofosbuvir after liver transplantation on recurrent HCV with different genotypes. OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of sofosbuvir and ribavirin in LDLT recipients with recurrent HCV genotype 4. PATIENTS AND METHODS: Thirty-nine Egyptian LDLT recipients were treated for recurrent HCV after LDLT with nucleos(t)ide analog NS5B polymerase inhibitor, sofosbuvir, and ribavirin without pegylated interferon for 6 months (November 2014 to June 2015) in this intention-to-treat analysis. RESULTS: One recipient died 1 week after starting the treatment, but the remaining 38 patients completed 24 weeks of treatment and were then followed for 12 weeks after end of treatment (EOT). The sustained virological response (SVR) at week 12 after EOT was achieved in 76% (29/38) of recipients. SVR was significantly higher in treatment-naïve patients and in recipients with a low stage of fibrosis. Only 2 (5%) recipients developed severe pancytopenia and acute kidney injury. CONCLUSIONS: We recommend initiating treatment as soon as possible after liver transplantation with newer combinations, such as ledipasvir/sofosbuvir or sofosbuvir/simeprevir, rather than sofosbuvir with Ribavirin, to achieve higher rates of SVR.

Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma.

There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA-urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features. We retrieved HCC characteristic lncRNAs, lncRNA-UCA1 and lncRNA-WRAP53, based on the microarray signature profiling (released by LncRNADisease database). Quantitative reverse-transcriptase polymerase chain reaction assay (RT-qPCR) was then used to evaluate the expression of selected lncRNAs in the serum of 160 participants. Furthermore, in 20 of 82 HCC cases involved in the study, we examined the expression of lncRNA-UCA1 and lncRNA-WRAP53 in 20 HCC tissues and adjacent nontumor tissues and analyzed its correlation with the serum level of these lncRNAs. The prognostic significance of the investigated parameters in HCC patients was explored. We found that lncRNA-UCA1 and lncRNA-WRAP53 were significantly higher in sera of HCC than those with chronic HCV infection or healthy volunteers. Our data suggested that the increased expression of UCA1 and WRAP53 was associated with advanced clinical parameters in HCC. Of note, tissue levels of the chosen lncRNAs strongly correlate with their sera level. The combination of both lncRNAs with serum alpha fetoprotein resulted in improved sensitivity to 100%. The median follow-up period was 21.5 months. LncRNA-WRAP53 was significant independent prognostic markers in relapse-free survival. LncRNA-UCA1 and lncRNA-WRAP53 upregulation may serve as novel serum biomarkers for HCC diagnosis and prognosis.