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1.
BMC Med Genomics ; 17(1): 202, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123171

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing. METHODS: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}. RESULTS: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes-identified across 10 genome sequencing studies-in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC. CONCLUSION: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients.


Subject(s)
Carcinoma, Hepatocellular , Exome Sequencing , Liver Neoplasms , Mutation , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Egypt , Middle Aged , Female , Genomics , Adult
2.
Transpl Int ; 36: 11240, 2023.
Article in English | MEDLINE | ID: mdl-37334014

ABSTRACT

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.


Subject(s)
Burnout, Professional , Health Workforce , Liver Transplantation , Female , Humans , Male
3.
Front Med (Lausanne) ; 9: 927744, 2022.
Article in English | MEDLINE | ID: mdl-36082268

ABSTRACT

Background: Bile stones are associated with numerous complications in liver transplant recipients. Endoscopic retrograde cholangiopancreatography (ERCP) has been proven to be safe and highly effective in dealing with most post-transplant biliary complications. Objective: The objective of this study was to identify the possible risk factors for bile stone formation on top of biliary stricture, the effects of stones on graft outcomes, and their management. Methods: This case-control study included 83 patients who underwent living donor liver transplant (LDLT) and suffered from postoperative biliary stricture with or without stones. Patients were divided into two groups. Group 1 (n = 55) included patients with biliary strictures with no stones and group 2 (n = 28) included patients who developed stones on top of biliary strictures. Data about the recipient and donor characteristics, surgical technique, blood lipid profile, immunosuppressive drugs, post-transplant complications, and interventions were collected from the medical records. Results: The frequency of hepatitis C virus (HCV) was significantly higher in group 2 compared to group 1 (71.4% vs. 47.3%, p = 0.036). The body mass index (BMI) of the donors was significantly higher in group 2 than in group 1 (25.17 ± 2.53 vs. 23.68 ± 2.63, p = 0.015). Episodes of acute rejection were significantly higher in group 2 than in group 1 (21.4% vs. 5.5%, p = 0.027). The ERCP was sufficient in most of the cases (89.2%) to ensure biliary drainage. The identified independent risk factors for biliary stones included HCV, biliary drain, donor's BMI, and serum cholesterol level. Conclusion: Positive HCV, biliary drain insertion, donor's BMI, and serum cholesterol level were independent risk factors for developing bile stones on top of biliary strictures. Biliary stones were associated with high episodes of acute graft rejection, and they could be successfully managed by the ERCP modality.

4.
World J Hepatol ; 14(6): 1150-1161, 2022 Jun 27.
Article in English | MEDLINE | ID: mdl-35978667

ABSTRACT

BACKGROUND: Patients who undergo living donor liver transplantation (LDLT) may suffer complications that require intensive care unit (ICU) readmission. AIM: To identify the incidence, causes, and outcomes of ICU readmission after LDLT. METHODS: A retrospective cohort study was conducted on patients who underwent LDLT. The collected data included patient demographics, preoperative characteristics, intraoperative details; postoperative stay, complications, causes of ICU readmission, and outcomes. Patients were divided into two groups according to ICU readmission after hospital discharge. Risk factors for ICU readmission were identified in univariate and multivariate analyses. RESULTS: The present study included 299 patients. Thirty-one (10.4%) patients were readmitted to the ICU after discharge. Patients who were readmitted to the ICU were older in age (53.0 ± 5.1 vs 49.4 ± 8.8, P = 0.001) and had a significantly higher percentage of women (29% vs 13.4%, P = 0.032), diabetics (41.9% vs 24.6%, P = 0.039), hypertensives (22.6% vs 6.3%, P = 0.006), and renal (6.5% vs 0%, P = 0.010) patients as well as a significantly longer initial ICU stay (6 vs 4 d, respectively, P < 0.001). Logistic regression analysis revealed that significant independent risk factors for ICU readmission included recipient age (OR = 1.048, 95%CI = 1.005-1.094, P = 0.030) and length of initial hospital stay (OR = 0.836, 95%CI = 0.789-0.885, P < 0.001). CONCLUSION: The identification of high-risk patients (older age and shorter initial hospital stay) before ICU discharge may help provide optimal care and tailor follow-up to reduce the rate of ICU readmission.

5.
J Transl Med ; 20(1): 342, 2022 07 30.
Article in English | MEDLINE | ID: mdl-35907883

ABSTRACT

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.


Subject(s)
MicroRNAs , Non-alcoholic Fatty Liver Disease , Probiotics , RNA, Long Noncoding , Animals , Hepatic Stellate Cells , Interleukin-6/metabolism , Liver/pathology , Liver Cirrhosis/pathology , MicroRNAs/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Probiotics/pharmacology , Probiotics/therapeutic use , RNA, Long Noncoding/metabolism , RNA, Messenger/metabolism , Rats , Transforming Growth Factor beta/metabolism
6.
Arab J Gastroenterol ; 23(3): 159-164, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35688682

ABSTRACT

BACKGROUND AND STUDY AIMS: Portal vein thrombosis (PVT) is no longer an absolute contraindication for living donor liver transplantation (LDLT). This study aimed to assess the short-term outcomes of LDLT and compare the 1-year survival rates between patients with and without preoperative PVT. PATIENTS AND METHODS: This combined prospective and retrospective cohort study was conducted on patients who underwent LDLT at Ain Shams Centre for Organ Transplantation (ASCOT) between 2008 and 2020. The study included 60 patients with PVT and 60 patients without PVT. The two groups were compared in terms of preoperative data, operative details, postoperative complications, and 1-year survival. RESULTS: Most patients with PVT were Child C (65%) and had higher model for end stage liver disease scores (16.23 ± 4.03) compared to the non-PVT group (13.9 ± 4.5). The PVT group showed longer cold ischemic time (CIT), hospital stay, and intensive care unit stay and significantly shorter 1-year survival rate (63.3%) compared to the non-PVT group (86.7%) (P = 0.003). Those with PVT grades I, II, and III had 1-year survival rates of 72.5%, 50%, and 40%, respectively. CONCLUSION: Preoperative PVT reduces the 1-year survival after transplantation, with patients with higher PVT grades exhibiting lower 1-year survival. LDLT for PVT still remains challenging and requires further studies.


Subject(s)
End Stage Liver Disease , Liver Diseases , Liver Transplantation , Venous Thrombosis , Child , End Stage Liver Disease/etiology , Humans , Liver Diseases/complications , Liver Transplantation/adverse effects , Living Donors , Portal Vein/surgery , Prospective Studies , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Venous Thrombosis/complications , Venous Thrombosis/surgery
7.
Clin Transplant ; 36(10): e14636, 2022 10.
Article in English | MEDLINE | ID: mdl-35343601

ABSTRACT

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).


Subject(s)
Liver Transplantation , Living Donors , Female , Humans , Living Donors/psychology , Preoperative Care , Liver , Pain , Randomized Controlled Trials as Topic
8.
World J Hepatol ; 13(10): 1405-1416, 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34786175

ABSTRACT

BACKGROUND: Despite significant advancements in liver transplantation (LT) surgical procedures and perioperative care, post-LT biliary complications (BCs) remain a significant source of morbidity, mortality, and graft failure. In addition, data are conflicting regarding the health-related quality of life (HRQoL) of LT recipients. Thus, the success of LT should be considered in terms of both the survival and recovery of HRQoL. AIM: To assess the impact of BCs on the HRQoL of live-donor LT recipients (LDLT-Rs). METHODS: We retrospectively analysed data for 25 LDLT-Rs who developed BCs post-LT between January 2011 and December 2016 at our institution. The Short Form 12 version 2 (SF 12v2) health survey was used to assess their HRQoL. We also included 25 LDLT-Rs without any post-LT complications as a control group. RESULTS: The scores for HRQoL of LDLT-Rs who developed BCs were significantly higher than the norm-based scores in the domains of physical functioning (P = 0.003), role-physical (P < 0.001), bodily pain (P = 0.003), general health (P = 0.004), social functioning (P = 0.005), role-emotional (P < 0.001), and mental health (P < 0.001). No significant difference between the two groups regarding vitality was detected (P = 1.000). The LDLT-Rs with BCs had significantly lower scores than LDLT-Rs without BCs in all HRQoL domains (P < 0.001) and the mental (P < 0.001) and physical (P = 0.0002) component summary scores. CONCLUSION: The development of BCs in LDLT-Rs causes a lower range of improvement in HRQoL.

9.
Egypt Liver J ; 11(1): 14, 2021.
Article in English | MEDLINE | ID: mdl-34777866

ABSTRACT

BACKGROUND: The current SARS-CoV-2 pandemic may negatively impact the care of liver transplant candidates and recipients. MAIN BODY OF THE ABSTRACT: Accordingly, each country must have its national guidelines based on the current situation and according to available tools. Liver Transplantation Scientific Committee of Waiting List Project in Egypt was established in 13 April 2020. One of the major objectives of this Scientific Committee is the preparation of national protocol for Transplant Centers in Egypt to deal with living donor liver transplantation (LDLT) during SARS-CoV-2 pandemic. CONCLUSIONS: The protocol highlights basic hospital requirements for LDLT during SARS-CoV-2 pandemic, the patient selection from the waiting list, management of patients on the waiting list, and post-transplant management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43066-020-00074-4.

10.
World J Hepatol ; 13(12): 2081-2103, 2021 Dec 27.
Article in English | MEDLINE | ID: mdl-35070010

ABSTRACT

BACKGROUND: Biliary complications (BCs) after liver transplantation (LT) remain a considerable cause of morbidity, mortality, increased cost, and graft loss. AIM: To investigate the impact of BCs on chronic graft rejection, graft failure and mortality. METHODS: From 2011 to 2016, 215 adult recipients underwent right-lobe living-donor liver transplantation (RT-LDLT) at our centre. We excluded 46 recipients who met the exclusion criteria, and 169 recipients were included in the final analysis. Donors' and recipients' demographic data, clinical data, operative details and postoperative course information were collected. We also reviewed the management and outcomes of BCs. Recipients were followed for at least 12 mo post-LT until December 2017 or graft or patient loss. RESULTS: The overall incidence rate of BCs including biliary leakage, biliary infection and biliary stricture was 57.4%. Twenty-seven (16%) patients experienced chronic graft rejection. Graft failure developed in 20 (11.8%) patients. A total of 28 (16.6%) deaths occurred during follow-up. BCs were a risk factor for the occurrence of chronic graft rejection and failure; however, mortality was determined by recurrent hepatitis C virus infection. CONCLUSION: Biliary complications after RT-LDLT represent an independent risk factor for chronic graft rejection and graft failure; nonetheless, effective management of these complications can improve patient and graft survival.

11.
Clin Res Hepatol Gastroenterol ; 45(4): 101517, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32900667

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/drug therapy , Liver Neoplasms/drug therapy
12.
Arab J Gastroenterol ; 21(2): 76-79, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32423854

ABSTRACT

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.


Subject(s)
Creatinine/blood , Fasting , Islam , Liver Transplantation , Postoperative Complications , Transplant Recipients , Egypt , Fasting/adverse effects , Fasting/blood , Female , Humans , Immunosuppression Therapy/methods , Kidney Function Tests/methods , Liver Transplantation/adverse effects , Liver Transplantation/methods , Male , Middle Aged , Monitoring, Physiologic/methods , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Renal Insufficiency/etiology , Renal Insufficiency/prevention & control , Transplant Recipients/psychology , Transplant Recipients/statistics & numerical data
13.
Transplant Proc ; 52(1): 227-232, 2020.
Article in English | MEDLINE | ID: mdl-32000940

ABSTRACT

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.


Subject(s)
Colonoscopy/statistics & numerical data , Liver Transplantation , Mass Screening/statistics & numerical data , Preoperative Care/statistics & numerical data , Adenoma/diagnosis , Adenoma/epidemiology , Aged , Colonic Neoplasms/diagnosis , Colonic Neoplasms/epidemiology , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colonoscopy/methods , Female , Humans , Liver Transplantation/methods , Living Donors , Male , Mass Screening/methods , Middle Aged , Odds Ratio , Preoperative Care/methods , Prevalence , Retrospective Studies , Risk Factors
14.
J Gene Med ; 21(9): e3112, 2019 09.
Article in English | MEDLINE | ID: mdl-31301261

ABSTRACT

BACKGROUND: The biology of hepatocellular carcinoma remains poorly understood. Long non-coding RNAs (lncRNAs) have been confirmed to be key regulators of most cell processes and cancer. The lncRNA cancer susceptibility candidate 2 (CASC2) was originally identified as a downregulated gene in endometrial cancer and acted as a tumor suppressor. The lncRNA taurine up-regulated gene 1 (TUG1) has been shown to play an oncogenic role in various cancers. However, the relative expression of CASC2 and TUG1 in hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) and the relationship between both remains unclear. The present study aimed to evaluate both lncRNA CASC2 and TUG1 relative gene expression in whole blood of HCC/HCV patients in relation to HCV and healthy subjects and to relate them to each other and to different clinicopathological factors. METHODS: The relative expression of CASC2 and TUG1 was estimated by a quantitative reverse transcriptase-polymerase chain reaction in 30 HCC/HCV patients and compared with 20 cases of HCV patients and 20 controls. RESULTS: CASC2 was downregulated in HCC/HCV patients, whereas TUG1 was overexpressed in relation to HCV and the control group, indicating their antagonistic effect. This suggests their role in the pathogenesis of HCC on top of HCV. Their expression was correlated to Barcelona Clinic Liver Cancer stage and serum alpha-fetoprotein level. CONCLUSIONS: CASC2 and TUG1 could be new potential biomarkers with a valid non-invasive technique.


Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , RNA Interference , RNA, Long Noncoding/genetics , Tumor Suppressor Proteins/genetics , Adult , Aged , Apoptosis/genetics , Carcinoma, Hepatocellular/diagnosis , Cell Line, Tumor , Cell Movement/genetics , Female , Humans , Leukocytes/metabolism , Liver Neoplasms/diagnosis , Male , Middle Aged , ROC Curve
15.
J Clin Pharm Ther ; 44(3): 447-453, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30714175

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The influence of immunosuppression on the response to antiviral therapy (AVT) for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients remains controversial, especially for the rarely investigated genotype 4. This study aims to compare the effects of the two widely used calcineurin inhibitors (CNIs) (cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to different AVT regimens. METHODS: A prospective, dual-centre, cohort study of 126 Egyptian living donor liver transplant (LDLT) recipients with recurrent HCV genotype 4 infection, who were categorized into three groups according to the AVT used. Group I received pegylated interferon (Peg-IFN-α 2a) plus ribavirin (RBV) (n = 44), group II received the direct antiviral agent (DAA) sofosbuvir plus RBV (n = 52) and group III received daclatasvir and sofosbuvir (also DAAs) plus RBV (n = 30). Each group was further subdivided according to the primary immunosuppression (CsA or Tac). The sustained virological response (SVR) and relapse rates were considered the primary therapeutic outcomes of AVT. RESULTS: No significant intergroup differences were observed in the achievement of primary and secondary outcomes. SVR rates in the IFN-based regimen were 75% and 66.7% in CsA and Tac users and 81.2% and 83% in DAAs, respectively. Relapse rates in the IFN-based regimen were 10% and 16.7% in CsA and Tac users and 12.5% and 14.9% in DAAs, respectively. WHAT IS NEW AND CONCLUSION: Within the limitations of a relatively small study, CsA did not offer an advantage over Tac regarding the response to AVT after HCV genotype 4 recurrence in LDLT recipients.


Subject(s)
Antiviral Agents/therapeutic use , Cyclosporine/therapeutic use , Hepatitis C, Chronic/drug therapy , Tacrolimus/therapeutic use , Adult , Aged , Calcineurin Inhibitors/therapeutic use , Drug Interactions/physiology , Drug Therapy, Combination/methods , Female , Genotype , Hepacivirus/drug effects , Humans , Immunosuppressive Agents/therapeutic use , Interferon-alpha/therapeutic use , Liver Transplantation/methods , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Prospective Studies , Recombinant Proteins/therapeutic use , Recurrence , Ribavirin/therapeutic use , Sofosbuvir/therapeutic use , Young Adult
16.
Arab J Gastroenterol ; 19(3): 116-120, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30268427

ABSTRACT

BACKGROUND AND STUDY AIMS: Studies have found increased expression of IL-23 in inflamed and non-inflamed mucosa of patients with ulcerative colitis (UC). We hypothesized that serum interleukin-23 as a non-invasive test has a role in pathogenesis of ulcerative colitis disease and correlates with the disease severity. PATIENTS AND METHODS: Forty patients with biopsy proven ulcerative colitis, recruited from Ain Shams University hospitals were included. Forty healthy subjects matched in age and gender were also included in the study as a control group. Serum IL-23 level was quantified using quantitative ELISA technique (Enzyme linked Immunosorbent Assay). RESULTS: Patients with UC had higher level of interleukin 23 (234.5 ±â€¯161 pg/mL) compared to control subjects (54.2 ±â€¯15 pg/mL) and the level of IL-23 correlated with the disease severity. Cut off value of IL-23 at 68 pg/mL was the best to differentiate between cases and control subjects. Receiver operating characteristic curve (ROC) revealed that the best cut off for IL-23 to detect mild cases of ulcerative colitis was at105 pg/mL, to detect moderate cases at 200 pg/mL and to detect severe cases was at 270 pg/mL with sensitivity 80% to mild cases, 60% to moderate cases and 81% to severe cases. CONCLUSION: Our findings confirm the suggestion that IL-23 level measurement may be of value as a non-invasive test in the diagnosis and disease severity assessment in patients with UC.


Subject(s)
Colitis, Ulcerative/blood , Interleukin-23/blood , Severity of Illness Index , Adult , Case-Control Studies , Colitis, Ulcerative/pathology , Female , Humans , Male , Middle Aged , ROC Curve
17.
Eur Radiol ; 28(12): 5356-5367, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29948070

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Fluorodeoxyglucose F18/pharmacology , Liver Neoplasms/diagnosis , Liver Transplantation , Positron Emission Tomography Computed Tomography/methods , alpha-Fetoproteins/metabolism , Adult , Aged , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/blood , Liver Neoplasms/therapy , Male , Middle Aged , Prospective Studies , Radiopharmaceuticals/pharmacology , Waiting Lists
18.
J Hepatocell Carcinoma ; 5: 29-36, 2018.
Article in English | MEDLINE | ID: mdl-29520343

ABSTRACT

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.

19.
Indian J Gastroenterol ; 37(2): 127-132, 2018 03.
Article in English | MEDLINE | ID: mdl-29532323

ABSTRACT

BACKGROUND/AIM: Portal vein tumor thrombosis (PVTT) is a common complication in hepatocellular carcinoma (HCC) and it was considered a relative contraindication for transarterial chemoembolization (TACE) by many centers. This study aimed to assess the outcomes after TACE in patients with branch PVT regarding Child classification, radiological response, and 1-year survival. METHODS: Thirty HCC patients (24 male, 6 females) Child A cirrhotics with branch PVT underwent TACE. Follow up was done at 1, 3, 6, and 12 months after first TACE. All patients underwent laboratory investigations including liver function tests to assess deterioration in liver functions and triphasic spiral computed tomography to assess radiological response according to modified response evaluation criteria in solid tumors (mRECIST) criteria, and survival analysis was recorded. RESULTS: TACE succeeded to achieve disease control in 93.3%, 86.3%, 57.7%, and 44.4% of patients after 1, 3, 6, and 12 months, respectively. Post-TACE liver decompensation occurred in the form of ascites in 30%, jaundice in 10%, and hepatic encephalopathy in 3.3% within 1 month of TACE. One month survival after TACE was 100%, 3 months was 96.6%, 6 months was 86.6%, and 1-year survival was 60%. Mean overall survival of the included patients was 17 months (SE = 1.59). CONCLUSION: TACE seems an alternative option for patients with unrespectable HCC with portal vein thrombosis in patients with good liver function tests.


Subject(s)
Carcinoma, Hepatocellular/complications , Chemoembolization, Therapeutic/methods , Liver Neoplasms/complications , Portal Vein , Venous Thrombosis/therapy , Aged , Chemoembolization, Therapeutic/mortality , Egypt , Female , Follow-Up Studies , Humans , Liver Function Tests , Male , Middle Aged , Survival Analysis , Survival Rate , Time Factors , Tomography, Spiral Computed , Treatment Outcome , Venous Thrombosis/classification , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology
20.
World J Hepatol ; 9(20): 896-904, 2017 Jul 18.
Article in English | MEDLINE | ID: mdl-28804572

ABSTRACT

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.

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