Expression of Matrix Metalloproteinases in Human Cystic Echinococcosis.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease caused by the Echinococcus granulosus senso lato (E. granulosus s.l.) larval stages. Parasitederived products have been shown to regulate host matrix metalloproteinases (MMPs), contributing to CE pathogenesis and progressive liver fibrosis in intermediate hosts. The current study aimed to investigate the potential role of MMP1, 7, 8, and 13 in E. granulosus s.l-induced liver fibrosis. METHODS: Thirty CE patients with active, transitional, or inactive hydatid cysts were enrolled in this study to determine the inductive effects of E. granulosus on the expression of MMP-1, MMP-7, MMP-8, and MMP-13 in healthy liver tissue and fibrotic liver tissue using qRT-PCR. RESULTS: According to the WHO-IWGE classification, patients with functional cysts (CE1 and CE2) had the highest percentage (46.6%). MMP-1, MMP-7, MMP-8, and MMP-13 expression levels were significantly higher in fibrotic liver than in normal liver tissue. MMP-13 and MMP-1 had the highest and lowest expression levels among MMPs. Compared to the normal group, the fold change for MMP-13 in the fibrotic group was greater than 12 and had the highest AUC value (AUC= 0.8283). CONCLUSION: Our findings suggest that E. granulosus-derived products might be involved in regulating host MMPs. Thus, MMPs may be considered potential biomarkers for predicting CE prognosis. Because of the non-normal distribution of our patients' CE types, further research, particularly on circulation MMPs, is needed to confirm the potential role of MMPs in CE pathogenesis and to follow up on CE patients.

Pancreas Transplant Alone in the USA, Where Do We Stand?

BACKGROUND: Currently, over 63,000 pancreas transplant procedures have been performed worldwide, with only approximately 8% of all pancreas transplants having been a pancreas transplant alone. Our study aimed to quantify outcomes following pancreas transplant alone in the United States from 2001 to 2020, with an emphasis on graft and patient survival. METHODS AND MATERIALS: We performed a retrospective registry analysis utilizing the OPTN/UNOS database for pancreas transplants alone performed in the United States from January 2001 to May 2020 to assess transplant outcomes. The study population was divided into two subgroups: patients receiving a pancreas transplant between 2000 and 2009 and those receiving a pancreas transplant between 2010 and 2020. RESULTS: 3008 allograft recipients were included in the study. 1679 (54.87%) transplants were done from January 2000 to the end of 2009. 1381 (45.13%) transplants were done from 2010 to May 2020. Although the BMI and recipient sex comparison indicate a statistically significant difference, the differences are not clinically significant. The overall 5-year allograft survival rate was 52.17% in the 2000-2009 group, which increased to 58.82% in pancreas transplants alone from 2010 to 2020 (P = 0.02). The overall 5-year patient survival rate was 74.52% in the 2000-2009 group, which increased to 74.92% in pancreas transplants alone from 2010 to 2020 (P = 0.81). CONCLUSION: With all the progress in terms of surgical techniques, organ allocation and preservation, and immunosuppressive regimens, the pancreas transplant alone allograft survival has been improving over the years, although it has been still being underutilized around the US.

Can Echinococcus granulosus-Derived MicroRNAs be Biomarkers for Diagnosis and Follow-up of Cystic Echinococcosis Patients?

INTRODUCTION: Cystic echinococcosis (CE) is a neglected tropical disease caused by the larval stages of Echinococcus granulosus (E. granulosus). MicroRNAs (miRNAs) are small noncoding RNAs acting as mediators in host-parasite interaction. Recently, numerous studies have been conducted on miRNAs in infectious diseases; however, little data are available about the role of miRNAs in pathogenesis and early diagnosis of CE. METHODS: The current study evaluated the expression of four E. granulosus-derived miRNAs, including egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71 in fibrotic and healthy liver tissues of 31 CE patients with active and inactive hydatid cysts by qRT-PCR. RESULTS: Of the 31 patients, 48.4% had active cysts (CE1 and CE2), while the remainder had transitional (16.1%) and inactive (35.5%) CE types cysts. The qRT-PCR analysis revealed a significant increase of 11.2, 9.91, 6.2, and 13.1-fold in the fibrotic tissue group for egr-miR-125,5p, egr-let-7,5p, egr-miR-2, and egr-miR-71, respectively. Among these miRNAs, egr-miR-125-5p exhibited the highest area under the curve (AUC) value of 0.8050 for predicting liver fibrosis. CONCLUSIONS: Our findings provide new data about the role of E. granulosus-derived miRNAs in pathogenesis of CE. The high AUC of egr-miR125,5p reflecting the possibility of using egr-miR125,5p as biomarker in CE diagnosis. Further studies on serum of CE patients are needed to confirm the potential role of circulating egr-miR-2a-3p and egr-miR-125-5p in the early diagnosis of CE.

Serum Level of egr-miR-2a-3p as a Potential Diagnostic Biomarker for Cystic Echinococcosis.

INTRODUCTION: Cystic Echinococcosis (CE) is a chronic parasitic disease caused by the metacestodes of Echinococcus granulosus senso lato (E. granulosus s.l.). The larval stages of this parasite, hydatid cyst, are usually diagnosed using imaging modalities and serological testing; however, several studies have recently suggested using the parasite-derived microRNAs (miRNAs) as novel diagnostic biomarkers. MATERIALS AND METHODS: The present study included 31 CE patients who were older than 5 years and were admitted to the hospitals of Ahvaz, Iran for hydatid cyst removal surgery during 2019-2021. The egr-miR-125-5p and egr-miR-2a-3p levels were evaluated in the sera of the CE patients before and 6 months after the surgery using Quantitative Real-Time PCR (qRT-PCR), and the results were compared with the serum samples from 15 healthy volunteers. Then, the intergroup comparisons were performed using the t test. RESULTS: The patients' age range was 6-72 years, with a mean age of 34.6 years. Moreover, based on the classification by the WHO-IWGE, one patient (3.2%) had CE1, 14 patients (45.2%) had CE2, 5 patients (16.1%) had CE3, 2 patients (6.5%) had CE4, and 9 patients (29%) had CE5. Also, 21 patients (67.74%) had a positive antigen test using the ELISA method, while 10 patients (32.26%) had a negative ELISA. The pre-operative expression level of egr-miR-2a-3p was 10.36 folds higher compared to 6 months after the surgery, with an AUC value of 0.8176. However, the expression levels of egr-miR-125-5p did not change significantly 6 months after the surgery compared to pre-operative levels. CONCLUSIONS: According to the present study results, the serum levels of egr-miR-2a-3p can be a promising non-invasive biomarker for diagnosing CE and monitoring its potential recurrence after cystectomy.

Evaluation of the Protoscolicidal Effectiveness of Hypertonic Saline, Silver Nitrate, Ethanol, Using Sponge Pad Method and Injecting into Fertile Hydatid Cysts.

Background: We aimed to evaluate currently protoscolices agents by using two methods including injection and impregnated sponges with protoscolices agents. Methods: Hypertonic saline 20%, silver nitrate 0.5% and Ethanol 96% were injected into sheep hydatid cysts. Then, after different exposure times (5, 10, and 15 min), the protoscolices were aspirated from the cyst and viability of the protoscolices were evaluated microscopically using vital staining. In the second part, the live protoscolices were sprayed on the soaked sponge with the mentioned protoscolicidal agents. After different exposure times live protoscolices were counted microscopically. One-way ANOVA and Tukey tests were used for showing difference significant between studied groups. Results: Cyst injection method showed that ethanol, Nacl and AgNo3 have 80%, 60% and 6% protoscolocidal efficacy, respectively (P<0.05). In sponge method the most and fastest protoscolocidal efficacy were observed in all used protoscolicidal agents. Conclusion: Ethanol and NaCl and AgNo3 with sponge method is more effective than the injection of protoscolices agents in the cyst.

The Role of Tissue Inhibitor of Metalloproteinase-1 and 2 in Echinococcus granulosus senso lato-Induced Human Hepatic Fibrosis.

INTRODUCTION: The main mechanism underlying hepatic fibrosis is the imbalance between tissue Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs). This study aimed to investigate the potential role of TIMP-1 and TIMP-2 in the process of hepatic fibrosis caused by Echinococcus granulosus senso lato (E. granulosus s.l.). METHODS: The expressions levels of TIMP-1 and TIMP-2 mRNAs were evaluated in fibrotic and normal hepatic tissues of 30 patients with Cystic Echinococcus (CE) using qRT-PCR. Moreover, their serum levels of TIMP-1 were assessed before CE cyst removal and 6 months after surgery using ELISA. RESULTS: The qRT-PCR results showed that the expression levels of TIMP-1 and TIMP-2 mRNAs were significantly higher in the fibrotic hepatic tissue compared to the normal liver tissue, in a way that the TIMP-1 and TIMP-2 mRNA expression levels were 19.07 and 6.58 folds higher in the fibrotic tissue compared to the normal liver tissue. Among these TIMPs, TIMP-1 exhibited the higher area under the curve (AUC) value for predicting liver fibrosis. However, we could not find a significant difference in the serum levels of TIMP-1 before and after the cyst removal procedure (p = 0.48). CONCLUSIONS: For the first time, our study showed that the significant overexpression of both TIMP mRNAs in the fibrotic liver tissue of the CE patients may be due to the increased expression of MMPs in the peri-cystic tissue. However, we could not find a significant difference in the pre- and post-operative TIMP-1 levels, which may be due to recurrence or heterogeneity in the cyst type. Therefore, performing further studies with a larger sample size of the CE patients is recommended.

Primary disseminated intraabdominal hydatidosis: a case report.

BACKGROUND: Hydatidosis, a zoonotic disease caused by the larvae of Echinococcus granulosus sensu lato (E. granulosus s.l.), can be primary or secondary. However, primary disseminated intraabdominal hydatidosis is a rare form of the disease, accounting for about 2% of all intraabdominal cysts. CASE PRESENTATION: We report herein a case of primary disseminated intraabdominal hydatidosis with multiple organ involvement in a 51-year-old Iranian man presenting to a healthcare facility with abdominal pain. During the physical examination, two abdominal masses were palpated. Ultrasound and computed tomography revealed six cystic lesions in the patient's liver, subhepatic region, pelvic, and omentum. Afterward, he underwent surgery, during which the cystic lesions were completely removed. The patient received albendazole (400 mg/kg/day) postoperatively and was recommended to continue the treatment for 4 months. CONCLUSIONS: Although primary disseminated intraabdominal hydatidosis is rare, this problem is of great importance due to the fertility of cysts and the high risk of recurrence. Therefore, it is recommended to follow such patients with imaging modalities and enzyme-linked immunosorbent assay for native antigen B (AgB). In addition, patients should undergo albendazole therapy postoperatively for 4 months.

Gene expression in human liver fibrosis associated with Echinococcus granulosus sensu lato.

Liver fibrosis is a dynamic process that occurs in response to chronic liver disease resulting from factors such as chronic infections, autoimmune reactions, allergic responses, toxins, radiation, and infectious agents. Among the infectious agents, multicellular parasites cause chronic inflammation and fibrosis. Twenty-five patients with different stages of cystic echinococcosis (CE) were enrolled in the study. The expression of ACTA2, COL3A1, IFN-γ, MMP2, MMP9, TGF-ß1, and TNF-α genes was determined by qRT-PCR in healthy and fibrotic liver tissue of the CE patients. TGF-ß1 expression was evaluated by immunohistochemistry, and histology was conducted to assess the development of liver fibrosis. Expression of MMP9, ACTA2, COL3A1, and MMP2 was found significantly higher in the fibrotic tissue compared to healthy tissue. We observed a significant correlation between TGF-ß1 and TNF-α gene expressions and liver fibrosis. The mRNA level of IFN-γ was lower in the fibrotic than in the healthy hepatic tissue. Immunohistochemistry analysis revealed TGF-ß1 upregulation in the fibrotic tissue. Histology showed inflammation and fibrosis to be significantly higher in the fibrotic tissue. The findings of this study suggest that Echinococcus granulosussensu lato can promotes fibrosis through the overexpression of TGF-ß1, MMP9, ACTA2, COL3A1, and MMP2. The downregulation of IFN-γ mRNA in fibrotic samples is probably due to the increased production of TGF-ß1 and the suppression of potential anti-fibrotic role of IFN-γ during advanced liver injury caused by E. granulosussensu lato.

A Young Man with Hemobilia Due to a Fistula between Hepatic Artery and Biliary Tract.

A 22-year-old man who had suffered two attacks of brisk upper gastrointestinal bleeding (UGIB) within a month prior to admission was diagnosed as having hemobilia because of fistula formation between the hepatic artery and intrahepatic bile duct due to inflammation and abrasion. He was managed by surgery.

Ameliorating effect of encapsulated hepatocyte-like cells derived from umbilical cord in high mannuronic alginate scaffolds on acute liver failure in rats.

OBJECTIVES: In this study, effects of encapsulated umbilical cord stem cells (UCSCs)-derived hepatocyte-like cells (HLCs) in high mannuronic alginate scaffolds was investigated on CCl4-induced acute liver failure (ALF) in rats. MATERIAL AND METHODS: UCSCs were encapsulated in high mannuronic alginate scaffolds. Then the UCSCs differentiated into HLCs for treatment of CCl4-induced ALF in rats. Thirty rats randomly divided into 5 groups: Intoxicated group received only CCl4 to induce ALF. In other groups including cell-free, UCSCs and HLCs, alginate scaffolds were transplanted into the liver 4 days after CCl4 injection. Biochemical markers including albumin (ALB), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. Histological changes and gene expression of ALB, alpha-fetoprotein (AFP), and cytokeratin 18 (CK-18) were also assessed. RESULTS: Expression of CK-18 significantly increased in HLCs compared to the UCSCs in vitro. This indicates that UCSCs can effectively differentiate into the HLCs. In CCl4-intoxicated group, BUN, AST and ALT levels, and histological criteria, such as infiltration of inflammatory cells, accumulation of reticulocytes, nuclear pyknosis of hepatocyte and sinusoidal dilation, significantly increased. In this group, ALB secretion significantly decreased, while AFP expression significantly increased. Both UCSCs and HLCs encapsulated in alginate scaffolds effectively attenuated biochemical tests, improved liver cytoarchitecture, increased expression of ALB and reduced AFP expression. CONCLUSION: Finding of the present study indicated that encapsulation of UCSCs or HLCs in alginate mannuronic scaffolds effectively improve CCl4-induced ALF.

The Comparison of the Effect of Mannitol and N Acetyl Cysteine on Liver Function in Partial Hepatectomy.

The alterations in liver function in patients after major liver resection are complex. Partial hepatectomy surgery is considered as a selective therapeutic approach in many benign and malignant liver tumors, secondary metastases, and liver trauma. According to surgical techniques most often based on vascular control and hepatic venous closure (Pringle maneuver), related complications such as ischemia and decreased venous return during and after surgery can be seen. In this study, the effects of Mannitol and N-acetylcysteine, on liver function, after hepatectomy surgery, were compared. This study was shown that infusion N-acetylcysteine next to mannitol, in partial hepatectomy surgeries, was not the significant difference to improve liver function, hemodynamic status, and laboratory tests.

Associating liver partition and portal vein ligation for staged hepatectomy: A surgical technique for liver resections.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel surgical technique liver resection in traditionally nonresectable primary intrahepatic tumors or colorectal liver metastases. MATERIALS AND METHODS: From June 2013 to March 2014, patients with primary tumor of liver or colorectal tumors with liver metastasis were selected to evaluate whether they met the initial criteria for ALPPS procedure. RESULTS: Nine patients enrolled in the study with primary diagnoses of colon and rectosigmoid cancer, carcinoid tumor, gastrointestinal stromal tumor of small intestine, hepatocellular carcinoma, and pancreatic neuroendocrine tumor (PNET). Four candidates excluded from the study prior or during the first step operation due to fatty liver, hepatic fibrosis, peritoneal seeding, and multiple small intestine metastases. Five patients underwent two stages of ALPPS with the interval of about 1 week. Liver hypertrophy was 100% among our candidates after the initial step. One postoperative death happened because of massive pulmonary thromboembolism Recurrence of liver metastasis was seen in one patient. Hepatic failure Class B and A were observed in two patients which did not progress during follow-up period. One patient developed an enterocutaneous fistula. DISCUSSION: We recommend to use 2 organ bags, one for wrapping right lobe and the other one for covering visceral organs and also do liver biopsy in suspicious cases of damaged liver parenchyma and laparoscopic exploration of abdomen for seeding and multiple metastases prior to laparotomy. CONCLUSION: As the procedure has not been well established and verified by oncologists yet, further studies are required to define the exact indications of ALPPS.

Effects of N-Acetylcysteine Addition to University of Wisconsin Solution on the Rate of Ischemia-Reperfusion Injury in Adult Orthotopic Liver Transplant.

OBJECTIVES: One of the main concerns in liver transplant is the prolonged ischemia time, which may lead to primary graft nonfunction or delayed function. N-acetylcysteine is known as a hepato-protective agent in different studies, which may improve human hepatocyte viability in steatotic donor livers. This study investigated whether N-acetylcysteine can decrease the rate of ischemia-reperfusion syndrome and improve short-term outcome in liver transplant recipients. MATERIALS AND METHODS: This was a double-blind, randomized, control clinical trial of 115 patients. Between April 2012 and January 2013, patients with orthotopic liver transplant were randomly divided into 2 groups; in 49 cases N-acetylcysteine was added to University of Wisconsin solution as the preservative liquid (experimental group), and in 66 cases standard University of Wisconsin solution was used (control group). We compared postreperfusion hypotension, inotrope requirement before and after portal reperfusion, intermittent arterial blood gas analysis and potassium measurement, pathological review of transplanted liver, in-hospital complications, morbidity, and mortality. RESULTS: There was no significant difference between the groups regarding time to hepatic artery reperfusion, hospital stay, vascular complications, inotrope requirement before and after portal declamping, and blood gas analysis. Hypotension after portal reperfusion was significantly more common in experimental group compared with control group (P = .005). Retransplant and in-hospital mortality were comparable between the groups. CONCLUSIONS: Preservation of the liver inside Univer-sity of Wisconsin solution plus N-acetylcysteine did not change the rate of ischemia reperfusion injury and short-term outcome in liver transplant recipients.

Five Years Survival of Patients After Liver Transplantation and Its Effective Factors by Neural Network and Cox Poroportional Hazard Regression Models.

BACKGROUND: Transplantation is the only treatment for patients with liver failure. Since the therapy imposes high expenses to the patients and community, identification of effective factors on survival of such patients after transplantation is valuable. OBJECTIVES: The current study attempted to model the survival of patients (two years old and above) after liver transplantation using neural network and Cox Proportional Hazards (Cox PH) regression models. The event is defined as death due to complications of liver transplantation. PATIENTS AND METHODS: In a historical cohort study, the clinical findings of 1168 patients who underwent liver transplant surgery (from March 2008 to march 2013) at Shiraz Namazee Hospital Organ Transplantation Center, Shiraz, Southern Iran, were used. To model the one to five years survival of such patients, Cox PH regression model accompanied by three layers feed forward artificial neural network (ANN) method were applied on data separately and their prediction accuracy was compared using the area under the receiver operating characteristic curve (ROC). Furthermore, Kaplan-Meier method was used to estimate the survival probabilities in different years. RESULTS: The estimated survival probability of one to five years for the patients were 91%, 89%, 85%, 84%, and 83%, respectively. The areas under the ROC were 86.4% and 80.7% for ANN and Cox PH models, respectively. In addition, the accuracy of prediction rate for ANN and Cox PH methods was equally 92.73%. CONCLUSIONS: The present study detected more accurate results for ANN method compared to those of Cox PH model to analyze the survival of patients with liver transplantation. Furthermore, the order of effective factors in patients' survival after transplantation was clinically more acceptable. The large dataset with a few missing data was the advantage of this study, the fact which makes the results more reliable.

Differentiation of adipose-derived stem cells into Schwann-like cells: fetal bovine serum or human serum?

Access to autologous Schwann cells is limited due to lack of donor site and its difficult isolation and culture. Therefore, one of the possible ways to obtain to Schwann cells is to differentiate mesenchymal stem cells into glial pathway using various materials and protocols. The aim of this study was to compare the effects of fetal bovine serum and human serum on Schwann cell differentiation of adipose-derived stem cells to choose the best serum for use in future research. For this purpose, after isolation of human adipose-derived stem cells, it was characterized and differentiated into Schwann cell lineage using two protocols which one of them contained fetal bovine serum and the other human serum. At the end, morphological evaluation declared an increased detachment of cells in response to human serum. On the other side, immunocytochemistry showed that there was a significant increase in the number of cells expressing glial fibrillary acidic proteins and S100 in fetal bovine serum-treated group when compared to human serum-treated one (P<0.05). It was concluded that fetal bovine serum was more effective than allogeneic human serum in Schwann cell differentiation of adipose-derived stem cells.

De novo malignancy after liver transplant.

OBJECTIVES: Patients who have liver transplant are at high risk of developing de novo malignancies. The purpose of this study was to evaluate incidence and histologic type of de novo malignancies after liver transplant in a liver transplant center. MATERIALS AND METHODS: In 1700 patients who had orthotopic liver transplant from deceased and living donors from January 1992 to October 2012, de novo malignancies after transplant were analyzed. RESULTS: There were 38 patients (2.2%) who developed de novo malignancy. Pathologic diagnosis was posttransplant lymphoproliferative disorder in 24 patients (63%), gastrointestinal adenocarcinoma in 4 patients (10%), Kaposi sarcoma in 3 patients (8%), pancreatic head adenocarcinoma in 2 patients (5%), papillary thyroid carcinoma in 1 patient (3%), lumbosacral multiple myeloma in 1 patient (3%), conjunctive carcinoma in 1 patient (3%), testicular cancer in 1 patient (3%), and metastatic adenocarcinoma to the vertebrae of unknown origin in 1 patient (3%). In the 24 patients who had posttransplant lymphoproliferative disorder, 20 patients (83%) were children aged <10 years, and 5 patients (21%) died of this disease. CONCLUSIONS: Posttransplant lymphoproliferative disorder was the most common malignancy among liver transplant recipients. This disease primarily involved children and was a major cause of morbidity and mortality. Preventive and early diagnostic strategies are justified to decrease morbidity and mortality from de novo malignancy after liver transplant.

En-bloc liver-pancreas transplant in Iran.

Liver transplant can be challenging in cirrhotic patients with diabetes mellitus. In chronic liver disease, the glucose metabolism is altered; uncontrolled diabetes negatively influences the outcome of liver transplantation and poses difficulty in the management of immediate post transplantation period. Simultaneous liver-pancreas transplantation is an option to prevent early complications due to diabetes and also to improve the quality of life after transplantation in patients with Insulin-Dependent Diabetes Mellitus (IDDM) and chronic liver disease. We report the first en-bloc liver-pancreas transplant done in the transplant history of Iran. We describe the technical details of the procedure as well as the short term outcome after transplantation. In this case report, we also discuss in some details, the surgical, medical and immunological advantages of combined liver-pancreas transplantation as opposed to separate implantation of both organs.

Clinical experience in organ transplant from the Shiraz Transplant Center: 2011.

OBJECTIVES: The Shiraz Organ Transplant Center, the largest transplant center in Iran, has expanded its program of organ transplant during recent years. This article seeks to summarize organ transplantation over the last 2 decades and evaluate its status as of 2011. MATERIALS AND METHODS: We retrospectively analyzed the clinical records of all organ transplants performed in our center in 2011. We reviewed the patients' demographics, underlying disease, operation details as well as postoperative complications. RESULTS: During this period, 655 organ transplants including 345 liver, 297 kidney, 29 pancreas, and 11 intestine and multivisceral transplants were done. Among 345 liver transplants, 291 patients received a deceased-donor graft including 18 cases of split liver transplants while 54 patients received living-donor liver transplants. The 1-year graft and patient survival rates were 90.1% and 91%. CONCLUSIONS: In recent years, our program in organ transplants has expanded in number and variety of organs transplanted. This improvement is related to our multidisciplinary strategies to expand the donor pool and the experiences obtained during our transplant activities.