Iman F. Montasser

Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported to be strongly expressed in HCC tissue hampering its extensive use in clinical practice. AIM To evaluate the clinical usefulness of serum SCCA levels as a serological marker for early detection of HCC among high-risk patients compared to AFP. MATERIALS AND METHODS The study comprised of three groups. Group A included 30 patients with CLD diagnosed based on clinical, laboratory, and ultrasonographical investigations; group B included 49 patients with HCC diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or liver biopsy; and group C, the control group, included 15 healthy subjects matched for age and sex. All groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including liver functions, viral markers, and AFP and SCCA estimation using ELISA technique. RESULTS This study revealed a highly significant difference between patients with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133 +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently elevated in patients with HCC with normal AFP levels representing its useful role in early detection and follow-up of patients treated for HCC. The area under the curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical significance. CONCLUSIONS SCCA could represent a useful tool as a marker for 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.

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.

Role of procalcitonin in diagnosis of bacterial infection in trans-arterial chemoembolisation treated hepatocellular carcinoma patients.

BACKGROUND AND STUDY AIM Trans-arterial chemoembolisation (TACE) became the treatment of choice for multinodular hepatocellular carcinoma. The use of prophylactic antibiotics following intervention is controversial. This study aimed to assess the role of serum procalcitonin level in early diagnosis of bacterial infection following TACE to optimise antibiotic intake in those patients. PATIENTS AND METHODS This study was carried on HCC patients diagnosed according to AASLD who underwent TACE and developed post interventional fever within 48 h. Laboratory investigations including CBC, neutrophil count, C-reactive protein and ESR (pre and after intervention) were done. Cultures were done according to the suspected site of infection. Serum procalcitonin was done for all the included patients before and after TACE. RESULTS Forty two TACE treated patients were included with post interventional fever within 48 h. Their ages ranged between 45 and 65 (mean 53.83 ± 5.23). All patients received antibiotic prophylaxis started 24h pre intervention and for 5 days after according to the local protocol. Five patients (11.9%) had positive blood cultures post intervention. The analysis of laboratory results showed statistical significant correlation between procalcitonin levels and positive cultures, post interventional CRP and TLC and pre interventional INR and bilirubin, while there was statistical significant correlation between CRP and post interventional temperature, total leucocytic count and site of focal lesion. CONCLUSION Procalcitonin seems to be a promising marker for diagnosis of sepsis in TACE treated HCC patients to optimise the unnecessary use of antibiotics.

Changing the face of fever of unknown origin in Egypt: a single hospital study

Infections remain the most frequent cause of fever of unknown origin (FUO) in developing countries. Some cases of fever remain a mystery and patients are discharged without knowing the cause. Prehospital healthcare facilities vary between countries, and even within the same country. FUO was first described in 1961 by Petersdorf and Beeson when they established the three criteria that define FUO: a minimum measured temperature of 38.3 C, febrile states occurring on several occasions over a period of at least three weeks, and a minimum of one week of investigations being required.1 The modern definition of FUO is based on modifications of these criteria taking into account four specific patient subtypes: classic, nosocomial, immunedeficient (neutropenic), and HIVassociated FUO.2,3 We outlined changes in causes of classic FUO according to the latest definition and compare the causes with those of a previous study conducted at the same hospital in 1974.4 We retrospectively reviewed 374 adult patients with FUO admitted to the Abbassia Fever Hospital under the definition outlined by Durack and Street (1991).5 Data were obtained from admission files. The patient population comprised 217 (58%) male patients, with a mean age of 40.2 ± 14.5 years. Further, 240 patients (64.2%) lived in urban areas, while 134 (35.8%) lived in rural areas. A continuous pattern of fever was found in 211 patients (58.3%), while 58 patients (16%) presented with a remittent pattern, and 87 patients (23.2%) showed intermittent fever symptoms. Six patients (1.6%) had relapsing fever. Blood cultures grew Gram-negative organisms in only nine cases (2.4%) and Gram-positive in eight cases (2.1%). Also, in urine cultures Gram-negative organisms were dominant including E. coli, Klebsiella and Enterobacter while Gram-positive cocci were only S. aureus. With regard to the final diagnosis, 248 patients (66.3%) were diagnosed with an infection etiology for FUO. Of these patients, 46 had cytomegalovirus infection (CMV). Among the non-infection patients, 49 (13.1%) were categorized in the miscellaneous group, and 29 (7.8%) were discharged without a final diagnosis (Table 1) Table 1 – Final diagnosis in the studied population.

Risk factors for early intrahepatic distant recurrence after radiofrequency ablation for hepatocellular carcinoma in Egyptian patients

Early tumor recurrence, either local or intrahepatic distant recurrence (IDR), after successful radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remains a significant problem. The study aimed to determine the potential risk factors for IDR within one year after successful RFA in HCC patients.

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.

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

ObjectiveTo 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 methodsThis 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.ResultsContrast-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.ConclusionContrast-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•18F-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 for18F-FDG PET positivity was >1.21• The ideal cut-off value for AFP was >202

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 ± 161 pg/mL) compared to control subjects (54.2 ± 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.

Living donor liver transplantation for high model for end-stage liver disease score: What have we learned?

AIM To assess the impact of model for end-stage liver disease (MELD) score on patient survival and morbidity post living donor liver transplantation (LDLT). METHODS A retrospective study was performed on 80 adult patients who had LDLT from 2011-2013. Nine patients were excluded and 71 patients were divided into two groups; Group 1 included 38 patients with a MELD score < 20, and Group 2 included 33 patients with a MELD score > 20. Comparison between both groups was done regarding operative time, intra-operative blood requirement, intensive care unit (ICU) and hospital stay, infection, and patient survival. RESULTS Eleven patients died (15.5%); 3/38 (7.9%) patients in Group 1 and 8/33 (24.2%) in Group 2 with significant difference (P = 0.02). Mean operative time, duration of hospital stay, and ICU stay were similar in both groups. Mean volume of blood transfusion and cell saver re-transfusion were 8 ± 4 units and 1668 ± 202 mL, respectively, in Group 1 in comparison to 10 ± 6 units and 1910 ± 679 mL, respectively, in Group 2 with no significant difference (P = 0.09 and 0.167, respectively). The rates of infection and systemic complications (renal, respiratory, cardiovascular and neurological complications) were similar in both groups. CONCLUSION A MELD score > 20 may predict mortality after LDLT.