Crosstalk between miR-215 and epithelial-mesenchymal transition specific markers (E-cadherin and N-cadherin) in different stages of chronic HCV Infection.

The main causes of death among patients with hepatocellular carcinoma (HCC) are a recurrence, metastasis, and deterioration of primary tumors by the epithelial-to-mesenchymal transition (EMT) which is controlled by several molecules including E-cadherin and N-cadherin. Microribonucleic acids (miRNAs) have been identified to play a regulatory role in EMT. miR-215 is important in repressing migration/invasion of cancer cells. In this study, we aimed to evaluate the crosstalk between miR-215 and EMT specific markers (E-cadherin and N-cadherin) with a spotlight on its role in the EMT process in hepatitis C virus (HCV)-infected patients. One hundred forty-five patients were studied, 75 had HCV-induced cirrhosis classified into child A, B, and C and 25 had HCC. In parallel, 45 healthy volunteers considered as controls. Serum levels of E- and N-cadherin were measured using enzyme-linked immunosorbent assay and miR-215 expression measured by a quantitative reverse transcription-polymerase chain reaction. Insignificant change in serum levels of E-cadherin and N-cadherin in HCV-infected patients compared with normal controls was observed with a slight increase in E-cadherin and N-cadherin in the child B group. HCC patients had the lowest amount of E-cadherin and N-cadherin compared with cirrhotic and normal subjects. A maximum reduction in miR-215 was observed in HCC patients compared with cirrhotic and control ones. A positive correlation (r = .202; P < .05) was observed between miR-215 and E-cadherin. Our data stressed on the potential role of miR-215 as an important mediator in HCC progression. miRNAs participating in EMT needs further studies to provide insight into the metastasis of HCC.

Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Insulin-like growth factor-2 (IGF-2) is an important autocrine and paracrine growth factor which may induce cell proliferation and inhibit cell apoptosis leading to the transformation of normal cells into malignant cells. This study aimed to evaluate the possible roles of IGF-2, insulin-like growth factor-2 receptor (IGF-2R), and insulin receptor substrate (IRS)-2 genes polymorphisms in susceptibility and clinicopathological features of HCC in Egyptian population. MATERIALS AND METHODS: Four hundred and twenty-six HCC patients and 334 controls were enrolled in the study. Polymorphisms of IGF-2+3580, IGF-2+3123, IGF-2R 1619, and IRS-2 1057 gene were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IGF-2 were determined using ELISA. RESULTS: Serum IGF-2 levels were significantly lower in HCC patients than in healthy controls. IGF-2+3580 AA genotype, IGF-2+3123 GG genotype or G allele, IRS-2 1057 DD genotype and D allele were significantly associated with HCC risk. The combination of IGF-2+3580 AA homozygosity and IGF-2R 1619 GG homozygosity presented a significant protective effect against HCC (OR=0.16,95% CI=0. 08-0.34, P=0. 005). Serum IGF-2 concentrations were significantly increased in HCC patients with the IGF-2+3580 AA genotype. We also observed that increased alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, and number of malignant lesions were accompanied by a significant increase of serum IGF-2 mean values of in HCC patients. CONCLUSION: IGF-2, IGF-2R, and IRS-2 genes polymorphisms and their combinations are associated with risk of HCC.

Successful use of venous graft from native liver with hepatocellular carcinoma during living donor liver transplantation with no impact on recurrence rate: A retrospective cohort study.

Introduction: There are still debates regarding using portal vein (PV) from liver with hepatocellular carcinoma (HCC) for vascular reconstruction. This study aimed to assess the feasibility and patency of PV venous graft from an explanted liver with HCC for the reconstruction of the hepatic veins tributaries or PV in living donor liver transplantation (LDLT) and to see if it has any risk on recurrence of HCC. Patient and methods: We conducted a retrospective study on 81 patients with HCC who underwent LDLT from April 2004 to July 2022. Results: Venous graft from native liver PV was used for vascular reconstruction in 31 patients as follows; reconstruction of V5 in 7 patients, V8 in 4 patients, V6 in 3 patients, combined V5 and V8 in 4 patients, V6 with V5/V8 in 5 patients, and as Y shape venous graft for 2 PV reconstruction in 8 patients. The implantation of the new conduit PV graft after reconstruction of the anterior sector tributaries was direct to the IVC in 8 patients, and to the common orifice of the left and middle hepatic veins in 12 patients. The 1 month, 3 months, and 1-year overall patency of the venous graft was 93.5%, 90.3%, and 84%, respectively. Nine patients had recurrent HCC. In multivariate analysis, the independent risk factors for HCC recurrence were AFP >400 ng/mL (HR = 1.47, 95% CI: 1.69-2.31, P = 0.01), moderate/poor differentiated tumor (HR = 3.06, 95% CI: 2.58-6.29, P = 0.02), and microvascular invasion (HR = 2.51, 95% CI: 1.05-1.93, P = 0.01). Using a PV venous graft had no risk factor for HCC recurrence (P = 0.9). Conclusion: The use of PV venous graft of native liver with HCC for venous reconstruction is a feasible and valuable option in LDLT with good patency rates and no risk of HCC recurrence.

Effect of treating chronic hepatitis C with direct-acting antivirals on extrahepatic cutaneous manifestations.

BACKGROUND: Hepatitis C virus (HCV) is a disease with a significant global impact, affecting approximately 2%-2.5% of the world's population. New direct-acting antivirals (DAAs) have been introduced over the past few years with great success in viral eradication. The association of chronic HCV infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature. AIM: To assess the effect of treating HCV with DAAs on the extrahepatic cutaneous manifestations of HCV. METHODS: This prospective observational study included 1039 HCV positive Egyptian patients who were eligible to receive DAAs. A total of 30 patients were diagnosed with extrahepatic cutaneous manifestations and fulfilled the inclusion criteria of the study. Of these patients, 6 had classic lichen planus, 8 were diagnosed with psoriasis vulgaris and 16 had pruritus. All patients received DAAs from October 2018 to July 2019 in the form of a three-month course of sofosbuvir/daclatasvir combination. Patients with lichen planus or psoriasis were dermoscopically evaluated before treatment and 6 mo after treatment, while patients with hepatic pruritus were assessed using the 12-Item Pruritus Severity Scale over the same period. RESULTS: All patients with psoriasis showed significant improvement in all psoriatic plaques, and all patients with hepatic pruritus scored 0 on the 12-Item Pruritus Severity Scale indicating total improvement of pruritus. In addition, four of six patients with lichen planus showed complete improvement. CONCLUSION: Treatment of HCV with DAAs was significantly effective in improving virus-related extrahepatic cutaneous manifestations.

Risk factors and management of different types of biliary injuries in blunt abdominal trauma: Single-center retrospective cohort study.

BACKGROUND: Biliary injuries after blunt abdominal traumas are uncommon and difficult to be predicted for early management. The aim of this study is to analyze the risk factors and management of biliary injuries with blunt abdominal trauma. METHOD: Patients with blunt liver trauma in the period between 2009 to May 2019 were included in the study. Patients were divided into 2 groups for comparison; a group of liver parenchymal injury and group with traumatic biliary injuries (TBI). RESULTS: One hundred and eight patients had blunt liver trauma (46 patients with liver parenchymal injury and 62 patients with TBI). TBI were; 55 patients with bile leak, 3 patients with haemobilia, and 4 patients with late obstructive jaundice. Eight patients with major bile leak and 12 patients with minor bile leak had been resolved with a surgical drain or percutaneous pigtail drainage. Nineteen patients (34.5%) with major and minor bile leak underwent successful endoscopic retrograde cholangiopancreatography (ERCP). Sixteen patients (29.1%) underwent surgical repair for bile leak. In Multivariate analysis, the possible risk factors for prediction of biliary injuries were central liver injuries (P = 0.032), high grades liver trauma (P = 0.046), elevated serum level of bilirubin at time of admission (P = 0.019), and elevated gamma glutamyl transferase (GGT) at time of admission (P = 0.017). CONCLUSION: High-grade liver trauma, central parenchymal laceration and elevated serum level of bilirubin and GGT are possible risk factors for the prediction of TBI. Bile leak after blunt trauma can be treated conservatively, while ERCP is indicated after failure of external drainage.

Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation.

AIM: To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome (SFSS) after living donor liver transplantation (LDLT). METHODS: Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT (A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range (0-144 m). RESULTS: SFSS was diagnosed in 20 (11.5%) of our recipients. While extra-small graft [small for size graft (SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis (P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis (P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10 (40%) SFSS vs 3/7 (42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe (RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10 (28.6%) SFSS vs 52/152 (34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7- and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference (P = 0.00). CONCLUSION: SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention (i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).

Verrucous Hemangioma Treated with Electrocautery.

Verrucous hemangioma is a rare vascular malformation consisting of a proliferation of dilated blood vessels of different sizes that occupy the dermis and hypodermis. The epidermis of the affected area shows a strong proliferative reaction that presents as a warty appearance. Here, we report the case of a 17-year-old male who presented with an asymptomatic warty growth above the lateral malleolus on the right leg, which healed after electrocautery.

Iatrogenic biliary injuries: multidisciplinary management in a major tertiary referral center.

Background. Iatrogenic biliary injuries are considered as the most serious complications during cholecystectomy. Better outcomes of such injuries have been shown in cases managed in a specialized center. Objective. To evaluate biliary injuries management in major referral hepatobiliary center. Patients & Methods. Four hundred seventy-two consecutive patients with postcholecystectomy biliary injuries were managed with multidisciplinary team (hepatobiliary surgeon, gastroenterologist, and radiologist) at major Hepatobiliary Center in Egypt over 10-year period using endoscopy in 232 patients, percutaneous techniques in 42 patients, and surgery in 198 patients. Results. Endoscopy was very successful initial treatment of 232 patients (49%) with mild/moderate biliary leakage (68%) and biliary stricture (47%) with increased success by addition of percutaneous (Rendezvous technique) in 18 patients (3.8%). However, surgery was needed in 198 patients (42%) for major duct transection, ligation, major leakage, and massive stricture. Surgery was urgent in 62 patients and elective in 136 patients. Hepaticojejunostomy was done in most of cases with transanastomotic stents. There was one mortality after surgery due to biliary sepsis and postoperative stricture in 3 cases (1.5%) treated with percutaneous dilation and stenting. Conclusion. Management of biliary injuries was much better with multidisciplinary care team with initial minimal invasive technique to major surgery in major complex injury encouraging early referral to highly specialized hepatobiliary center.