Pancreatic cyst fluid interleukin-1 beta (IL-1ß) level in predicting the risk of malignancy in pancreatic cysts.

Pancreatic cystic lesions (PCLs) may be accidentally discovered in up to 13.5% of cases. These PCLs are of multiple types, including mucinous cysts (intra-ductal papillary mucinous neoplasms [IPMN] and mucinous cystic neoplasms [MCN]) that have a risk of malignant transformation. The difficulty in differentiation between the various PCLs and their unpredictable risk of malignant transformation makes their management difficult. The new diagnostic tools of PCLs often include endoscopic ultrasound guided fine needle aspiration (EUS-FNA) for pancreatic cyst fluid analysis. This study aimed to determine if cystic fluid IL-1ß can predict the risk of malignancy and the degrees of dysplasia of pancreatic cysts. The study included 50 PCL patients. They were subjected to radiological, biochemical, serological, and histopathological examinations. Pancreatic cyst fluid IL-1ß was analyzed using an ELISA. Our data indicated that cyst fluid IL-1 ß can differentiate between benign and malignant cysts at cut-off value >150 pg/ml; with sensitivity and specificity of 84.00% and 56.00% respectively. Also, cyst fluid IL-1 ß can differentiate between mucinous and non- mucinous pancreatic cysts at cut-off value >150 pg/ml; with a sensitivity and specificity of 83.33% and 53.78%, respectively. However, cyst fluid IL-1 ß cannot differentiate between degrees of dysplasia of IPMN. In conclusion, our study suggested that pancreatic cyst fluid IL-1ß can differentiate between.

Vitamin D assessment in patients with COVID-19 virus and correlation with severity.

Background: Vitamin D may play a vital role in preventing the multi-system consequences of COVID-19 infections. The aim of this study is to evaluate the potential association between mean serum levels of vitamin D and COVID-19 and its correlation with severity and mortality. Results: A case-control study conducted on 80 Egyptian patients admitted at Ain Shams University designated hospitals, Cairo, Egypt, from March 2021 to September 2021. Regarding the laboratory investigations, we found that COVID-19 cases have significantly lower lymphocytic counts than controls. Regarding vitamin D, this study showed a statistically significant positive correlation between vitamin D and lymphocytes, and there were statistically significant negative correlations between vitamin D, neutrophil-lymphocyte ratio, C-reactive protein, blood urea nitrogen, serum creatinine, aspartate aminotransferase, alanine aminotransferase, ferritin, lactate dehydrogenase, and D-dimer. Conclusion: This study confirms that vitamin D deficiency is associated with the severity of COVID-19 clinically and laboratory.

Impact of biliary complications on quality of life in live-donor liver transplant recipients.

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.

Biliary complications in recipients of living donor liver transplantation: A single-centre study.

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.

M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals.

BACKGROUND: Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis. AIM: To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs. METHODS: From December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay. RESULTS: All patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001). CONCLUSION: M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.

Novel Application of the Traditional Lipid Ratios as Strong Risk Predictors of NASH.

PURPOSE: Limited data are available regarding the role of triglycerides, cholesterol and lipoproteins ratios as risk factors for nonalcoholic fatty liver disease (NAFLD) progression. In the present study, the investigators aimed to investigate the value of cardiovascular risk ratios of triglycerides, cholesterol, and lipoproteins as predictors of nonalcoholic steatohepatitis (NASH) and the correlation of such ratios with disease severity. PATIENTS AND METHODS: This study included 131 overweight and obese patients with NAFLD who were divided into NASH, borderline NASH, and non-NASH fatty liver (NNFL) subgroups according to NAFLD activity score (NAS) in liver biopsy, and 60 healthy participants as a control group. Lipid profile and lipid ratios including triglycerides/HDL (TGs/HDL), low-density lipoprotein/high-density lipoprotein (LDL/HDL) and total cholesterol/HDL (TC/HDL) ratios were measured. RESULTS: Significantly higher triglycerides/HDL ratio was found in NASH and borderline NASH, while higher cholesterol/HDL ratio was found in borderline NASH in comparison to controls. There were positive correlations between TGs/HDL and steatosis, ballooning, inflammation, BMI, and NAS; between LDL/HDL and inflammation; and between cholesterol/HDL and BMI, steatosis, and NAS. The highest AUC was that of TG/HDL (0.744), at a cut-off point of 3, with 71.8% sensitivity and 76.8% specificity. CONCLUSION: Triglycerides, cholesterol and lipoprotein ratios showed higher levels in NASH and correlated with NAFLD severity, and above these cut-off ratios, we can rule in the NASH cases which confer also the cardiovascular morbidities. Structured lipid ratios could serve as markers to screen NASH progression from simple steatosis cases and clarify the link of NASH with the cardiovascular risk prediction in overweight and obese patients.

In vitro knock-out of miR-155 suppresses leukemic and HCV virus loads in pediatric HCV-4-associated acute lymphoid leukemia: A promising target therapy.

Hepatitis C virus (HCV) infection is a major public health problem, having a high prevalence in Egypt. Leukemia and lymphoma have been associated with HCV infection. MicroRNA-155 (miR-155) has been reported to play a regulatory role in cancer, inflammation, and immune response to infection. The expression level of miR-155 in HCV viremic patients is controversial; although high miR-155 levels were demonstrated in HCV genotypes 1,2, and 3, low levels of miR-155 were detected in Egyptian patients with HCV genotype 4. Several studies have investigated the correlation between the levels of miRNA-155 and the replication of HCV, others have evaluated miRNA-155 as a prognostic biomarker in different types of cancer. No studies have investigated the impact of miRNA-155 knockdown on HCV pediatric patients associated with childhood acute lymphoblastic leukemia (ALL). We knocked-out the miR_155a in cultured polymorphonuclear cells (PBMCs) obtained from 60 children with ALL; 30 were associated with HCV-4 infection and 30 were HCV negative. The miR_155a, HCV viral load, and cell proliferation werre assessed in treated and untreated cells using TaqMan assay quantitative polymerase chain reaction. We found that miRNA-155 was significantly upregulated by seven folds in the HCV-4 associated ALL group; while being linked to high HCV viral load and leukemic burden, miR_155a knock-out can improve the disease outcome. We conclude that miR-155 is a critical miRNA that is considered a therapeutic target in pediatric HCV leukemic patients.

Evaluation of interleukin 23 (IL-23) as a non-invasive test of disease severity in patients with ulcerative colitis.

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.

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.

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.

Serum ferritin as a non-invasive marker in the prediction of hepatic fibrosis among Egyptian patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Many studies have found a relationship between hepatic iron, serum ferritin, and non-alcoholic fatty liver disease (NAFLD) or its progress. The aim of this study is to assess the value of serum ferritin as a non-invasive marker in the prediction of hepatic fibrosis in NAFLD. METHODS: This study included 113 subjects who were classified into three groups. Group I included 30 healthy subjects as control with no clinical, radiological, and histological features of NAFLD. Group II included 31 NAFLD patients without hepatic fibrosis. Group III included 52 patients with hepatic fibrosis on top of NAFLD. RESULTS: Serum ferritin was determined using ferritin ELISA kit. Fibrosis 4 score was calculated. Liver biopsy was conducted for included patients. Significantly higher levels of serum ferritin were found in patients with hepatic fibrosis on top of NAFLD than controls. Receiver operating characteristic curve analysis revealed that an optimum cutoff level of 51.95 ng/mL was the best to predict fibrosis on top of NAFLD with diagnostic sensitivity and specificity of 65% and 60%, respectively, and area under the curve = 0.658. CONCLUSION: Higher serum ferritin was found in patients with hepatic fibrosis on top of NAFLD. Serum ferritin was found to be a predictor of fibrosis on top of NAFLD with moderate sensitivity and specificity.

Reversibility of minimal hepatic encephalopathy following liver transplantation in Egyptian cirrhotic patients.

AIM: To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS: This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS: Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ≥ 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION: Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.

Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus.

BACKGROUND AND OBJECTIVES: Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). SUBJECTS AND RESULTS: 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×10(6) to 191×10(6). There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. CONCLUSION: SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis.