Autoantibodies profile in autoimmune liver diseases and chronic viral hepatitis.

Despite their low prevalence, autoimmune liver diseases (AILD) cause liver cirrhosis, progress and leads to mortality from liver failure. Autoantibodies are confirmed to have significance in the early screening of AILD patients, especially in those who are asymptomatic before onset of clinical signs. This study aimed to assess levels of liver autoantibodies and their association with clinical manifestations of autoimmune liver diseases and chronic viral hepatitis (CVH) patients. This case-control study included 50 patients (case group of 25 patients with AILD and control group of 25 patients with CVH). They were investigated for presence of antibodies against LKM-1, AMA-M2, PML, M2-3E (BPO), gp210, Sp100, LC-1, Ro52 and SLA/LP using the line immune blot technique, and for the presence of antinuclear antibodies (ANA), as non-organ specific autoantibodies, using indirect immunofluorescence technique. Specific autoantibodies were detected in all AILD cases and some of their levels were significantly higher when compared with CVH group. Among AILD patients, 52% were positive for ANA, whereas 61.1% of chronic hepatitis C and 28.6% of chronic hepatitis B patients were positive for ANA with no significant difference (p=0.3). In conclusion, early diagnosis of autoimmune liver diseases has been linked to assessment of autoantibodies, allowing for prompt therapeutic intervention to stop the progression of liver cirrhosis and the accompanying complications.

Schistosomal (bilharzial) polyps: Travel through the colon and beyond.

Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not uncommon presentation of this infection. Although the colon is the most commonly affected organ, many other organs are affected. S. polyps are associated with a variable range of morbidity independent of the Schistosomal infection. S. polyps are frequently described in endemic areas and increasingly reported in non-endemic areas mainly among immigrants and visitors to the endemic areas. This review aimed to increase awareness of practitioners, especially gastroenterologists, for this peculiar type of polyps caused by this neglected infection hence improving patient outcomes. Web-based search of different databases was conducted for the literature focusing the development of S. polyps in the colon and other organs with analysis of the clinical manifestations, diagnosis and treatment. The following key words were used in the search, "Schistosomiasis" OR "Bilharziasis" AND "Polyps" OR "Polyp" AND "Colon" OR "Small intestine" OR " Duodenum" OR " Stomach" OR "Esophagus" OR " Gallbladder" OR" Pharynx" OR "Larynx" OR "Trachea" OR "Urinary bladder" OR " Ureter" OR "Renal Pelvis" OR "Urethra". All publication types including case reports, case series, original research, and review articles were retrieved and analyzed. S. polyps are not infrequent presentation of acute or chronic Schistosomal infection. S. polyps are described in many organs including the bowel, genitourinary tract, skin, gallbladder and the larynx. Presentation of S. polyps is variable and depends on the site, number as well as the polyp size. The relationship of S. polyps to malignant transformation is a matter of discussion. Presence of S. polyps is sometimes the only manifestation of Schistosomiasis. Small polyps can be treated medically with praziquantel, while large accessible polyps are amendable for endoscopic excision through different polyp resection techniques. However, huge, complicated, non-accessible and suspicious polyps are indicated for surgical management or advanced endoscopic resection when appropriate. Clinicians and endoscopists should be aware about these facts when treating patients living in, immigrated from or visiting endemic areas.

Post-cholecystectomy iatrogenic bile duct injuries: Emerging role for endoscopic management.

Post-cholecystectomy iatrogenic bile duct injuries (IBDIs), are not uncommon and although the frequency of IBDIs vary across the literature, the rates following the procedure of laparoscopic cholecystectomy are much higher than open cholecystectomy. These injuries caries a great burden on the patients, physicians and the health care systems and sometime are life-threatening. IBDIs are associated with different manifestations that are not limited to abdominal pain, bile leaks from the surgical drains, peritonitis with fever and sometimes jaundice. Such injuries if not witnessed during the surgery, can be diagnosed by combining clinical manifestations, biochemical tests and imaging techniques. Among such techniques abdominal US is usually the first choice while Magnetic Resonance Cholangio-Pancreatography seems the most appropriate. Surgical approach was the ideal approach for such cases, however the introduction of Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was a paradigm shift in the management of such injuries due to accepted success rates, lower cost and lower rates of associated morbidity and mortality. However, the literature lacks consensus for the optimal timing of ERCP intervention in the management of IBDIs. ERCP management of IBDIs can be tailored according to the nature of the underlying injury. For the subgroup of patients with complete bile duct ligation and lost ductal continuity, transfer to surgery is indicated without delay. Those patients will not benefit from endoscopy and hence should not do unnecessary ERCP. For low-flow leaks e.g. gallbladder bed leaks, conservative management for 1-2 wk prior to ERCP is advised, in contrary to high-flow leaks e.g. cystic duct leaks and stricture lesions in whom early ERCP is encouraged. Sphincterotomy plus stenting is the ideal management line for cases of IBDIs. Interventional radiologic techniques are promising options especially for cases of failed endoscopic repair and also for cases with altered anatomy. Future studies will solve many unsolved issues in the management of IBDIs.

Biliary stent migration: why, how, and what?

BACKGROUND AND PURPOSE: The frequency, risk factors as well as the sites of biliary stent migration are variable in the literature. This retrospective study investigated the frequency of biliary stent migration, why biliary stents migrated, how the migrated stents affected the patients, and what are the different techniques retrieved the migrated stents. PATIENTS AND METHODS: Out of 876 stented patients, 74 patients (8.4%) had their stents migrated. Patients with and without migrated stents were compared regarding endoscopy and stent-related parameters. The sequels of stent migrations were reported. Furthermore, the methods used for stent retrieval were reviewed. RESULTS: Proximal and distal stent migration occurred at a rate of 3 and 5.5%, respectively. The independent predictors for stent migration were moderate to marked common bile duct (CBD) dilation, complete sphincterotomy, the use of balloon dilation, and stent insertion for more than 1 month. Cholangitis and stent obstruction was the most commonly reported adverse event (n = 18, 24.3%). Distal stent migration associated with two cases of bleeding due to duodenal wall injury, and two cases of duodenal perforation. All the retained migrated stents in the current study were retrieved by endoscopy using extraction balloon, Dormia basket, snares, and foreign body forceps. CONCLUSION: Biliary stent migration occurs at a rate of 8.4%. Stents do migrate because of dilated CBD, wide sphincterotomy, and biliary balloon dilation. Furthermore, wide, straight stents inserted for more than 1 month easily migrate. The migrated stents migrated intraluminal in the CBD, duodenum or the colon. All the retained migrated stents were retrieved endoscopically.

Huge bilharzial polyp mimicking colon cancer.

Bilharziasis (Schistosomiasis) is the third devastating tropical disease globally and is endemic in many countries including Egypt. The pathology of chronic colonic schistosomiasis results from egg-induced immune response, granuloma formation, and associated fibrotic changes that may manifest as bloody diarrhea, cramping, and, eventually, inflammatory colonic polyposis. Huge polyps complicating schistosomiasis are not frequently reported in the literature. Also, huge polyps as a sole manifestation of intestinal bilharziasis are rather rarely reported. Here, we report an Egyptian male patient who presented with bleeding per rectum with a huge polyp on colonoscopy, with morphological traits that mimicked colon cancer and proved to be of bilharzial etiology after surgical excision.

Circulating methylated RUNX3 and SFRP1 genes as a noninvasive panel for early detection of colorectal cancer.

OBJECTIVE: This study was conducted to assess the methylation status of runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1) genes in paired tissue and serum samples of colorectal cancer (CRC), adenomatous, and control subjects and elucidate the association between methylation status on RUNX3 and SFRP1 mRNA expression. METHODS: Methylation status of RUNX3 and SFRP1 in paired tissue and serum samples and RUNX3 and SFRP1 mRNA expression in tissue from 85 patients with CRC, 40 with adenoma, and 40 healthy controls were determined using methylation-specific PCR and reverse transcription PCR. RESULTS: The frequency RUNX3 and SFRP1 genes methylation was significantly higher in both tissues and serum of CRC patients and was significantly associated with absence of its corresponding mRNA expression. The concordance between tissue and serum methylation status was 94.4% for RUNX3 and 94.3% for SFRP1. Tissue RUNX3 methylation status detected CRC with 63.53% sensitivity and 80.00% specificity, while serum RUNX3 methylation status detected CRC with 60.00% sensitivity and 82.50% specificity. Tissue SFRP1 methylation status showed a sensitivity of 82.35% and specificity of 65.00%, while serum SFRP1 methylation status showed a sensitivity of 77.65% and specificity of 70.00% in detection of CRC. RUNX3/SFRP1/carcinoembryonic antigen (CEA) panel identified CRC with sensitivity of 89.41% in tissue and 84.71% in serum. CONCLUSION: Our results verified the reliability of using serum RUNX3 and SFRP1 methylation status as a noninvasive biomarker for diagnosis of CRC and that combined detection of RUNX3/SFRP1/CEA panel might be a promising strategy for early detection of CRC.

Double plastic stenting for inoperable malignant biliary stricture among cirrhotic patients as a possible cost-effective treatment: a pilot study.

BACKGROUND AND STUDY AIM: Endoscopic retrograde cholangiopancreatography (ERCP) has evolved as the main therapeutic intervention for hepatobiliary disorders. Palliative stenting for inoperable cases is associated with better morbidity and mortality than surgery. This work aimed at assessing the effect of insertion of two plastic stents in inoperable malignant biliary stricture among cirrhotic patients regarding stent patency, quality of life (QOL), and cost. PATIENTS AND METHODS: This multicenter study included 72 cirrhotic patients presented for ERCP with an inoperable malignant biliary stricture. All patients underwent ERCP after preoperative optimization with sphincterotomy, balloon dilatation, and insertion of two plastic stents of 10 Fr. Evaluation included stent patency at 6 months, effect on the QOL using EORTC QLQ-C30 (version 3), adverse events, and the cost. RESULTS: Patients included 67% of males and had an age range of 48-88 years (mean: 70 years). In all, 92% of stents were patent at 6 months. Significant improvement in serum total bilirubin and all items of QOL questionnaire at 6 months after the procedure was reported. Cholangitis and pancreatitis were reported in 25 and 8% of cases, respectively. The cost of insertion of two plastic stents and the daily cost of the procedure regarding the effect on QOL were low. CONCLUSION: Double plastic stenting of the common bile duct seems effective at 6 months of follow-up among cirrhotic patients with inoperable malignant biliary obstruction. Furthermore, it seems also valuable in improving laboratory findings and QOL among those patients with an acceptable cost.

RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma.

BACKGROUND: DNA methylation status is one of the most prevalent molecular alterations in human cancers. Identification of powerful diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) without a biopsy is urgently required. OBJECTIVE: The purpose of this study was to determine the methylation status of RASSF1A and SOCS-1genes as a non-invasive biomarker for HCC identification and prognosis. METHODS: Methylation specific-PCR technique was performed to recognize the methylation status of RASSF1A and SOCS-1 genes in 100 patients with HCC, 100 patients with liver cirrhosis (LC) but without HCC were considered as cirrhotic liver control group and 100 healthy control. RESULTS: Methylation of RASSF1A and SOCS-1 genes were detected in 40% and 38% of HCC patients respectively, 14% and 20% of LC patients respectively. Methylation of SOCS-1 gene in peripheral blood of healthy control was 23%. Methylation of RASSF1A gene was associated with age, tumor size, vascular invasion and α fetoprotein (AFP), while SOCS-1 gene methylation was significantly associated with tumor size and AFP. Furthermore, using RASSF1A/ SOCS-1/ AFP panel improve diagnostic sensitivity for HCC 86% and specificity of 75%. CONCLUSION: RASSF1A and SOCS1 genes methylation status may play an important role in the process of hepatocarcinogenesis and may be used as diagnostic and prognostic noninvasive biomarkers for HCC when combined with serum AFP.

Large Balloon Dilatation Versus Mechanical Lithotripsy After Endoscopic Sphincterotomy in the Management of Large Common Bile Duct Stones in Cirrhotic Patients: A Randomized Study.

BACKGROUND AND STUDY AIM: Removal of large common bile duct (CBD) stones is one of the challenges faced during endoscopic retrograde cholangiopancreatography, and it seems more difficult in cirrhotic patients because of suspected higher rates of adverse events, especially bleeding diathesis. This study aimed at comparing the success rate and complications between mechanical lithotripsy (ML) and large balloon dilation (LBD) after endoscopic sphincterotomy in patients with liver cirrhosis. PATIENTS AND METHODS: Ninety-eight cirrhotic patients with calcular obstructive jaundice were included and randomly divided into 2 groups: group A comprising 49 patients treated by LBD and group B comprising 49 patients treated by ML. All patients underwent sphincterotomy initially. All patients were subjected to thorough history taking and complete clinical examination. Pancreatic enzyme concentrations were measured 4 hours before and 24 hours after the procedure, and complete blood cell count and liver function tests were performed before and the morning after the procedure. Before and during endoscopic retrograde cholangiopancreatography, stone size and number were verified. RESULTS: The success rate for CBD clearance was 98% and 93.8% for LBD and ML, respectively. The rate of adverse events in this study was 10.2% (10/98), and bleeding was the commonest reported complication (5/10). Group B developed more (16.3%) adverse events than group A (4.1%), and the difference was statistically significant (P=0.04). CONCLUSION: Endoscopic sphincterotomy followed by LBD is a safe and effective treatment for large CBD stones in cirrhotic patients in comparison with sphincterotomy followed by ML.

Real time endoscopic ultrasound elastography and strain ratio in the diagnosis of solid pancreatic lesions.

AIM: To evaluate the accuracy of the elastography score combined to the strain ratio in the diagnosis of solid pancreatic lesions (SPL). METHODS: A total of 172 patients with SPL identified by endoscopic ultrasound were enrolled in the study to evaluate the efficacy of elastography and strain ratio in differentiating malignant from benign lesions. The semi quantitative score of elastography was represented by the strain ratio method. Two areas were selected, area (A) representing the region of interest and area (B) representing the normal area. Area (B) was then divided by area (A). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated by comparing diagnoses made by elastography, strain ratio and final diagnoses. RESULTS: SPL were shown to be benign in 49 patients and malignant in 123 patients. Elastography alone had a sensitivity of 99%, a specificity of 63%, and an accuracy of 88%, a PPV of 87% and an NPV of 96%. The best cut-off level of strain ratio to obtain the maximal area under the curve was 7.8 with a sensitivity of 92%, specificity of 77%, PPV of 91%, NPV of 80% and an accuracy of 88%. Another estimated cut off strain ratio level of 3.8 had a higher sensitivity of 99% and NPV of 96%, but with less specificity, PPV and accuracy 53%, 84% and 86%, respectively. Adding both elastography to strain ratio resulted in a sensitivity of 98%, specificity of 77%, PPV of 91%, NPV of 95% and accuracy of 92% for the diagnosis of SPL. CONCLUSION: Combining elastography to strain ratio increases the accuracy of the differentiation of benign from malignant SPL.

Emerging Role of Probiotics in the Management of Helicobacter pylori Infection: Histopathologic Perspectives.

BACKGROUND: There is growing evidence from preclinical and clinical studies that emphasizes the efficacy of probiotics in the management of Helicobacter (H) pylori infection; it increased the eradication rate, improved patient clinical manifestations and lowered treatment associated side effects. AIM: In this review we documented the potential ability of probiotics to ameliorate H. pylori induced histological features. MATERIALS AND METHODS: We searched the available literature for full length articles focusing the role of probiotics on H. pylori induced gastritis from histologic perspectives. RESULTS: Probiotics lowered H. pylori density at the luminal side of epithelium, improved histological inflammatory and activity scores both in the gastric corpus and antrum. This effect persists for long period of time after discontinuation of probiotic supplementation and this is probably through an immune mechanism. CONCLUSIONS: The current evidence support the promising role of probiotics in improving H. pylori induced histopathological features both in gastric antrum and corpus and for long periods of time. Because increased density of H. pylori on the gastric mucosa is linked to more severe gastritis and increased incidence of peptic ulcers, we can infer that a reduction of the density might help to decrease the risk of developing pathologies, probably the progression toward atrophic gastritis and gastric adenocarcinoma. These effects together with improving the H. pylori eradication rates and amelioration of treatment related side effects might open the door for probiotics to be added to H. pylori eradication regimens.

Hemobilia and Melena After Liver Biopsy: A Case Report and Review of Literature.

Liver biopsy is the gold standard for assessment of hepatic fibrosis although it is associated with many complications. We reported a 28-year-old chronic HCV patient who developed gall bladder hematoma with hemobilia and melena after liver biopsy. The hematoma resolved with conservative management.

Cytokines genes polymorphisms in chronic hepatitis C: impact on susceptibility to infection and response to therapy.

BACKGROUND: Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection, the production of abnormal cytokine levels appears to contribute in the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes polymorphisms located within the coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the study was to evaluate the association of of IL28B rs12979860, TGF-ß1-509, TNF-α 308, and IL-10-1082 polymorphisms with the susceptibility to hepatitis C virus genotype 4 infection and response to pegylated interferon-α and ribavirin therapy. METHODS: IL28B, TGF-ß1 and TNF-α genes polymorphisms were genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay while IL-10 gene polymorphism was detected by sequence specific primer-PCR in 220 healthy individuals and 440 hepatitis C infected patients (220 sustained virological response and 220 non-responder to combination therapy). RESULTS: IL28 B CT and TT, TGF-ß1 CT and TT and TNF-α AG and AA genotypes were significantly associated with susceptibility to hepatitis C infection and response to therapy. While no association was found between IL-10 gene polymorphism and susceptibility to HCV infection and response to treatment. CONCLUSIONS: These results suggested that inheritance of IL28B CT and TT, TGF-ß1 CT and TT and TNF-α AG and AA genotypes which appear to affect the cytokine production may be associated with susceptibility to HCV infection and resistance to combined antiviral therapy.

Influence of transforming growth factor-ß1 and tumor necrosis factor-α genes polymorphisms on the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND: Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. This study aimed to evaluate transforming growth factor-ß1 (TGF-ß1)-509 and tumor necrosis factor-α (TNF-α)-308 genes polymorphisms as a risk factors for cirrhosis and hepatocellular carcinoma (HCC) in chronic hepatitis C patients. MATERIALS AND METHODS: Two hundred and eighty HCV patients (152 patients with cirrhosis, 128 patients with HCC) and 160 controls were enrolled in the study. Polymorphisms of TGF-ß1-509 and TNF-α-308 gene were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum TGF-ß1 and TNF-α were determined using ELISA. RESULTS: TGF-ß1-509 TT, TNF-α-308 AA and GA genotypes frequencies were significantly increased in cirrhotic and HCC groups. Serum TGF-ß1 and TNF-α level were significantly increased in TGF-ß1-509 TT and TNF-α-308 AA genotypes respectively. CONCLUSION: TGF-ß1-509 and TNF-α-308 genes polymorphisms are associated with risk of liver cirrhosis and HCC in patients with chronic HCV infection.

Interleukin-4 polymorphisms and response to combination therapy in Egyptian chronic hepatitis C patients.

In hepatitis C infection, the production of inappropriate cytokines levels may contribute to viral persistence and may affect the response to antiviral therapy. We investigate the effect of IL4 C-590T and C-33T polymorphisms on the response to combination therapy with interferon and ribavirin in chronic HCV patients. These single nucleotide polymorphisms were determined by PCR-RFLP in 235 responder and 210 non-responder to combination therapy. The IL4-590 T/T and -33 T/T genotypes were associated with resistance to the therapy (p<0.001, p=0.001 respectively). Haplotypes T(-590) T(-33) and T(-590) C(-33) were associated with a higher risk in non-responder patients than the responders (p<0.001 for each) while frequency of haplotype C(-590) C(-33) (with all wild alleles) was significantly higher in responders as compared to non-responders (p<0.001). These results suggest that inheritance of the IL4 polymorphisms may be associated with resistance to combined antiviral therapy in Egyptian HCV patients.

MAGE-3 and MAGE-4 genes as possible markers for early detection of metastases in hepatitis C virus Egyptian patients complicated by hepatocellular carcinoma.

The dissemination of hepatocellular carcinoma (HCC) cells into the circulation plays a critical role in post-operative recurrence and metastasis. Early detection of metastatic tumor cells is critical to identify HCC patients at high risk of relapse. MAGE-3 and -4 genes were evaluated by reverse transcription polymerase chain reaction for the possibility of using them as new markers for early detection of metastases in 160 chronic HCV Egyptian patients, 115 of them were complicated with HCC. The expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with metastatic HCC were 36 and 52%, respectively. While the expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with localized HCC were 12.5 and 15%, respectively. Moreover, at least one type of mRNA was found in the peripheral blood of 68% of the metastatic HCC patients and in 20% of the localized HCC patients. While neither the controls nor the cirrhotic patients show expression of MAGE-4 mRNA in their peripheral blood. MAGE-3 and MAGE-4 may be a promising diagnostic tool for monitoring the prognosis of HCC patients and early detection of occult hematogenous metastasis of HCC.

Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient.

We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy.

Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma.

Hereditary hemochromatosis and alpha-1antitrypsin deficiency are genetic diseases characterized by endoplasmic reticulum (ER) stress with subsequent development of liver disease. Our aim was to estimate the frequency of hemochromatosis gene (HFE) mutant alleles (C282Y and H63D) and alpha-1 antitrypsin S/Z variants among Egyptian HCV cirrhotic patients and in hepatocellular carcinoma patients and to evaluate their effects on disease progression. HFE and alpha-1 antitrypsin polymorphisms were characterized in 200 Egyptian patients with HCV infection (100 patients complicated with cirrhosis, 100 patients with HCC) and 100 healthy subjects who had no history of any malignancy. The frequencies of HD genotype of H63D mutation were significantly increased in HCC patients compared to control group and to cirrhosis group. Also, the frequencies of DD genotype were significantly increased In HCC group compared to control group and to cirrhosis group. Our results suggested that Carriers of the D allele of H63D mutation were significantly more likely to develop HCC.