Arab Journal of Gastroenterology - Articles in Press

End-points in hepatitis B treatment - Corrected Proof

Nancy Leung — 2010-03-08

High prevalence of viral hepatitis B infection is associated with chronic hepatitis and serious liver diseases. The health burden of chronic hepatitis B (CHB) is high in Asia-Pacific region and, to a certain extent, significant in many Eastern European countries, Middle East, and certain part of Africa. Whether recent advances in chronic hepatitis B therapy can soon revert this is still controversial. However, gathering evidence showed that effective viral suppression is usually followed by normalization of serum alanine aminotransferase, resolution of histologic necroinflammation. Progression of fibrosis can be prevented by therapy, and the excitement is the demonstration of regression of fibrosis and reversion of cirrhosis, thereby improving the quality of life of the patients.

Left paraduodenal hernia causing acute small bowel obstruction - Corrected Proof

Shilpi Gupta, Onkar Singh, Ankur Hastir, Glossy Sabharwal — 2010-03-08

Abstract: Paraduodenal hernias are rare fascinating variety of hernias that arise in the potential spaces and folds of the posterior parietal peritoneum adjacent to the ligament of Treitz. These may present with chronic intermittent abdominal pain, acute small bowel obstruction or bowel ischaemia. Treatment is by surgery. We present a case of a 32-year-old male who had previously presented to us on multiple occasions with abdominal pain that had always relieved by its own. Only this time he presented with acute intestinal obstruction. The anatomy, management and significance of considering this uncommon diagnosis while examining a patient with acute small bowel obstruction are discussed.

Hepatitis A virus in Middle East countries: More evidence needed - Corrected Proof

Nastaran Mahboobi, Saeid Safari, Seyed Moayed Alavian — 2010-03-08

Hepatitis A virus (HAV) infection accounts for 75% of all cases of hepatitis in the world and approximately about 1.5 million symptomatic cases of hepatitis A occur annually in the world . This infection can easily spread by close contact with infected persons, by contaminated food, water and blood products . Prevalence of HAV infection differs greatly in various parts of the world according to the geographic area, sanitary conditions and socioeconomic levels . There are several reports about a shifting epidemiological pattern of HAV from high prevalence to lower endemicity as a result of improved living conditions from all over the world, even in underdeveloped and developing countries . Although this seems to be desirable, reports exist on higher risk of outbreaks among the adult population who have not been exposed to HAV in their life before and are, therefore, not immune . An effective strategy to protect non-immune populations against this disease is necessary. To achieve this, or at least, to evaluate the necessity of protecting susceptible populations, estimating the global prevalence of HAV, especially the epidemiological features in areas like the Middle East in which HAV is known to be endemic is mandatory. In spite of HAV endemicity in Middle East countries, there are not enough up to date data on the current situation of the disease. In this respect, there are great variations between different Middle East countries and even between various parts of the same country in some regions due to difference in sanitary and socioeconomic levels . The prevalence rates of anti-HAV antibodies has been demonstrated to vary in different parts and among different populations of the same country . For instance, the prevalence rate in Children less than 15years of age was 20.1%, 29%, 30.2%, 22.3% and 50% in United Arab Emirates , in Turkey , in Saudi Arabia , in Iran and in Egypt , respectively but it was higher in Lebanon and Syria according to published reports. Although this variation can be attributed to differences in design of various studies, yet an important factor remains different sanitary conditions and hygienic improvements in various parts of the studied countries. Hepatitis A virus is mainly transmitted via the faecal-oral route by a person to person spread, contaminated food products, contaminated water supplies, shellfish, oysters, fresh fruits and vegetables like green onions, tomatoes, strawberries, raspberries and even their frozen products . Water sources contaminated by sewage has been reported as the most likely identified responsible factor in some outbreaks, especially in developing countries . Travelling from low prevalence countries to those with higher prevalence has been reported as a causative factor . The booming tourism industry in the Middle East recommends efficient protective ways against hepatitis A.

Large pancreatic hydatid cyst presenting with obstructive jaundice - Corrected Proof

M. Boubbou, S. Boujraf, N.H. Sqalli, M. Maaroufi, S. Tizniti — 2010-03-08

Abstract: Primary hydatid disease of the pancreas is very rare. We report about the case of a 38-year-old man who presented with jaundice, abdominal pain and epigastric mass. Abdominal ultrasound and computed tomography (CT) scan demonstrated a large, thick-walled pancreatic cystic mass compressing the common bile duct and causing obstructive jaundice.The treatment involved eccentration and the resection of the protruding mass by cystogastrostomy. The procedure was successful and no recurrence or complication occurred postoperatively.Hydatid disease should be considered in the differential diagnosis of all cystic masses in the pancreas, especially in the geographical regions where the disease is endemic.

Using a recombinant single chain antibody for targeting liver myofibroblasts with anti-fibrogenic therapeutics - Corrected Proof

2010-03-02

Abstract: Chronic liver disease results in a liver scarring response termed fibrosis. Excessive scarring leads to cirrhosis which is associated with high morbidity and mortality. The only treatment for liver cirrhosis is liver transplantation, therefore much attention has been directed toward therapies that will slow or reverse fibrosis. Although anti-fibrogenic therapeutics have been shown to be effective in experimental animal models, licensed therapies have yet to emerge. A potential problem for any anti-fibrogenic therapy in the liver is the existence of the body’s major drug metabolising cell (the hepatocyte) adjacent to the primary fibrosis-causing cell, the myofibroblast. A human recombinant single chain antibody that binds to the surface of myofibroblasts was therefore developed. This antibody bound specifically to myofibroblasts in fibrotic mouse livers. When conjugated with a compound that stimulates myofibroblast apoptosis, the antibody directed the specific apoptosis of myofibroblasts with greater specificity and efficacy than the free compound. The antibody also reduced the side-effect of liver macrophage apoptosis and – in contrast to the free compound – reversed fibrosis in the sustained injury model used. These data suggest that specifically stimulating the apoptosis of liver myofibroblasts using a targeting antibody has potential in the treatment of liver fibrosis.

Insulin resistance and liver fibrosis progression in patients with chronic hepatitis C virus infection - Corrected Proof

Mohamed Yaqoot Abdel-Azziz, Kkaled Refaat Zalata, Mahmoud M. El-Bendary — 2010-03-02

Abstract: Background and study aims: Hepatitis C virus (HCV) infection can predispose to development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicating that diabetes might be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. This study aims to determine the prevalence of insulin resistance in non-diabetic patients with chronic hepatitis C and its relation to liver fibrosis.Patients and methods: This study included a cohort of 38 patients with chronic liver diseases. They were subdivided into two groups: chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Twelve age- and sex-matched healthy subjects were considered as the control group. The cohort was subjected to careful history and complete examination stressing upon the signs and symptoms of chronic liver diseases. Investigations include liver function tests, viral markers (anti-HCV antibodies and polymerase chain reaction (PCR) for HCV), serum fasting glucose, serum fasting insulin and homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound.Results: Liver fibrosis was found to be considerably more severe among HCV patients with elevated serum transaminases levels. No correlation between viral load and hepatic fibrosis in HCV-infected patients was found. Insulin resistance was present in HCV-infected cases compared with the control group and it correlated with liver fibrosis positively.Conclusion: The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non-diabetic patients with chronic HCV. Follow-up of hyperinsulinaemia by serial measurement of HOMA test in non-diabetic HCV-infected patients may be a biochemical indicator for progression of liver fibrosis.

Helicobacter pylori infection in Saudi children; clinical, endoscopic and pathological findings - Corrected Proof

Omar I. Saadah — 2010-03-02

Abstract: Background and study aims: Helicobacter pylori (H. pylori) infection is common in the Saudi paediatric population. The aim of this study was to describe the clinical presentation, endoscopic abnormalities and associated histopathological changes in a group of Saudi children with H. pylori infection.Patients and methods: This is a chart review of all Saudi children diagnosed at King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia, between September 2001 and July 2005 with H. pylori infection.Results: A total of 230 children were identified. One hundred and thiry six (55%) were females. The mean age was 11±3.9 years (range, 2–17). Thirty-two (14%) were underweight and 12 (5%) were stunted. The main symptom was epigastric pain in 128 (56%). Nodular gastritis was the most frequent endoscopic finding in 94 patients (40%). The histopathological findings in the antrum showed moderate chronic inflammatory activity in 65%, mild glandular atrophy in 14% and intestinal metaplasia in 2%. In the corpus, moderate chronic inflammatory activity was found in more than 50%, glandular atrophy in 7%, and no cases with intestinal metaplasia. The density of H. pylori in the antrum was mild in 67% and moderate in 26% of cases. In the corpus, it was mild in 49% and moderate in 21% of patients.The mean gastritis score was 4.2±1.3 in the antrum and 3.4±1.3 in the corpus. Nodular gastritis was associated with the highest mean gastritis score of 4.9±1.2 in the antrum (ANOVA<0.001). The severity of gastritis in the antrum and the corpus was associated with higher density of H. pylori (ANOVA<0.001).Conclusion: Saudi children with H. pylori infection were commonly found to have abnormal endoscopic findings which were associated with significant gastric mucosal inflammation.

Randomized trial comparing human albumin and hydroxyethyl starch 6% as plasma expanders for treatment of patients with liver cirrhosis and tense ascites following large volume paracentesis - Corrected Proof

Ehab E. Abdel-Khalek, Salah E. Arif — 2010-02-26

Abstract: Background and study aims: Cirrhosis is the commonest cause of ascites accounting for almost 85% of all cases. Approximately 10% of patients with cirrhosis develop diuretic-resistant tense ascites that requires other therapeutic interventions. Large-volume paracentesis with plasma expander infusion, mainly albumin, has been used for the management of ascites in cirrhotic patients. We aimed at investigating whether human albumin can be substituted by a less expensive plasma expander, hydroxyethyl starch 6% following paracentesis.Patients and methods: One-hundred and thirty-five patients (60% with cirrhosis and schistosomal periportal fibrosis combined, 26.7% with posthepatitic cirrhosis and 13.3% with schistosomal periportal fibrosis) with tense ascites were randomized to treatment by one-session of a nearly-total paracentesis plus intravenous human albumin (68 patients) or hydroxyethyl starch 6% (67 patients). These were given at a dose of 8g/l of ascitic fluid removed. The two groups were compared for incidence of complications, recurrence of massive ascites after hospital dismissal and survival rate.Results: Both groups showed no significant changes in renal or hepatic function or serum electrolytes. The incidence of complications following paracentesis was similar in both groups. The number of readmissions during follow up and causes of readmission and survival were also comparable. The effect of paracentesis on the effective intravascular volume was indirectly assessed by plasma renin activity and plasma aldosterone concentration before treatment, 2 and 6days after treatment. None of the mean values of these changed significantly in the two groups after paracentesis. Postparacentesis transient hypotension was observed more in the hydroxyethyl starch 6% group than in those treated with albumin (23.9% versus 8.8%, p=0.018).Conclusions: Hydroxyethyl starch 6% is safe and as effective as human albumin in protecting patients treated with nearly-total paracentesis from developing renal and electrolyte complications. Transient hypotension following paracentesis was, however, commoner in the hydroxyethyl starch group.

Pathology of NASH and fibrosis - Corrected Proof

Puja Sakhuja — 2010-02-25

Abstract: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease that has gained recognition in the last two decades. It may even account for some of the cases previously diagnosed as cryptogenic cirrhosis. Association of this entity with obesity, insulin resistance and type-II diabetes is well documented. In this review, patterns of liver fibrosis in NASH, its pathogenesis and staging systems are discussed.

Non-invasive systems for staging compensated cirrhosis - Corrected Proof

Massimo Pinzani — 2010-02-24

Progressive fibrosis and cirrhotic transformation of liver tissue are common pathological outcomes of most chronic liver diseases (CLDs). Although the histopathological analysis of liver tissue still represents the reference standard for the evaluation of disease progression in CLD, a distinct change in clinical practice is currently occurring and the tendency to substitute liver biopsy with ‘non-invasive methods’ has grown to a level of complexity that needs clarification and guidance.

Association of MnSOD Ala16Val genotype and activity with hepatocellular carcinoma risk in HCV-infected Egyptian patients - Corrected Proof

Amany Ibrahim, Shymaa Abd El-Azim, Marwa Abd El-Azim — 2010-02-24

Abstract: Background and study aims: Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. Chronic infection with hepatitis C virus (HCV) is a risk factor for HCC occurrence. HCV infection causes oxidative stress in hepatic cells through overproduction of reactive oxygen species (ROS) that cause carcinogenesis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that quenches free radicals. Ala16Val MnSOD polymorphism has been associated with cancer. It results from substitution of T to C at nucleotide 47 causing a change of valine to alanine on the 16th residue of 24-amino acid of mitochondrial-targeting sequence (MTS) of MnSOD.This work aimed to assess the relationship between MnSOD Ala16Val genotype and activity and HCC development in HCV-infected Egyptian patients.Patients and methods: This study was conducted on 75 HCV-infected HCC patients, 24 asymptomatic HCV-infected patients and 58 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis. MnSOD activity was measured using a superoxide dismutase assay kit.Results: The HCC group included 56 males and 19 females. The mean±standard deviation (SD) of their age was 53.3±1.85 years. The Ala/Ala genotype frequency in HCC patients (36.0%) was significantly higher than that in asymptomatic HCV-infected patients (12.5%, p=0.029) and in the healthy controls (18.9%, p=0.031). There was a significant difference between MnSOD activity in HCC patients and those in asymptomatic HCV-infected patients and healthy controls (p=0.000). Moreover, there was a highly significant increase in MnSOD activity in HCC patients with Ala/Ala and Val/Ala than in those with Val/Val genotypes (p=0.007).Conclusion: There is an evidence of association between Ala16Val MnSOD polymorphism and HCC occurrence in HCV-infected Egyptian patients. Furthermore, serum MnSOD activity was significantly higher in those patients compared to control subjects.

Targeting fibrosis with selective drug carriers - Corrected Proof

Klaas Poelstra, Rick Greupink, Leonie Beljaars — 2010-02-22

Abstract: This review summarises the progress that has been made in recent years in the field of drug delivery to the hepatic stellate cells (HSCs). HSCs are the crucial cells in the pathogenesis of liver fibrosis and consequently the main target cell for antifibrotic therapies. To enhance cell specificity, such antifibrotic drugs can be coupled to drug carriers that accumulate in this cell type. In recent years, several drug carriers directed at HSCs have become available and many drugs have now been coupled to these carriers. Using this strategy, high drug accumulation in HSCs has been achieved. Several drugs, such as kinase inhibitors, viral vectors, apoptosis-inducing drugs and drugs that inhibit cell proliferation or inflammation, have been targeted to HSCs. Receptor-mediated endocytosis subsequently leads to the release of internalised drugs and the pharmacological effects of these drugs have been demonstrated in HSCs. The selective delivery of drugs to HSCs may therefore provide a new approach to study crucial pathways or new treatments in liver fibrosis. This method may also be applied to those drugs whose adverse effects have prevented their systemic application in the past.

Molecular basis and clinical endopoints for the development of antifibrogenic drugs - Corrected Proof

Massimo Pinzani — 2010-02-22

The last two decades have witnessed a considerable progress in the understanding of the mechanisms responsible for the fibrogenic progression of chronic liver diseases. However, no drugs have been approved as antifibrotic agents in humans. Considering the central role attributed to hepatic stellate cells (HSCs) in liver fibrosis, this cell type has represented, and still represents, a major focus of antifibrotic research. Indeed, the well-described pathway of HSC activation, subsequent fibrogenesis, with the potential for apoptosis and reversibility, provides a logical framework to define the sites of intervention. Consequently, the search for effective antifibrogenic strategies is based on the knowledge gained in the area of HSC biology, including the biology of the factors (growth factors, cytokines, etc.) conditioning their pro-fibrogenic attitude. Regardless, it is absolutely clear that the best antifibrogenic treatment would be represented by any strategy able to eliminate the primary cause of parenchymal damage, metabolic overload or excessive oxidative stress. Since the fibrogenic process is essentially a compensatory phenomenon aimed at maintaining a sufficient tissue continuity and cohesion in the presence of a continuous microscopic parenchymal collapse, it would be erroneous to attempt to cure fibrogenic chronic liver diseases (CLDs) only with antifibrogenic drugs, once some effective compounds will become available for clinical use. Once this primary requirement is fulfilled, the association with an antifibrogenic drug would be relevant for stabilising the cure and favour an optimal remodelling. Putative antifibrogenic drugs include:

Hepatic progenitor cells in acute and chronic liver disease: Clinical aspects - Corrected Proof

Frederik Nevens, Aezam Katoonizadeh, Tania Roskams — 2010-02-19

In humans, increasing evidence supports the existence and activation of hepatic progenitor cells (HPCs) in different liver diseases, which are all characterised by a variable degree of hepatocyte loss and damage with impaired regeneration of remaining hepatocytes and/or bile duct epithelial cells . In chronic hepatitis, progenitor cell expansion is an important source of hepatocyte regeneration. The degree of activation and differentiation towards hepatocytes correlates with the degree of inflammatory activity and with the stage of the disease as well . However, little is known in humans about the response of HPCs in advanced stages of liver failure, such as acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).

A note from the Editor’s desk - Corrected Proof

Gamal Shiha — 2010-02-19

Hepatic fibrosis is a hot topic in basic and clinical hepatology. I had the honor of organizing the APASL single topic conference on hepatic fibrosis (Cairo 2008) and secured the participation of the leading world experts in this field. Their reviews cover the basic, translational and clinical aspects of liver fibrosis. The progress in defining novel approaches to the diagnosis and therapy of hepatic fibrosis is clearly demonstrated by the experts; moreover, the concept of fibrosis reversibility is emerging as a reality and its evaluation in large clinical trials for antifibrotic and antiviral drugs is highly recommended.

Steatosis, fibrosis and hepatitis C virus infection - Corrected Proof

Daniel Dhumeaux — 2010-02-17

Hepatic steatosis is a common histological feature in chronic hepatitis C. Its prevalence varies between 40% and 85% (mean 55%), depending on the characteristics of the population studied in terms of alcohol intake, overweight, diabetes and other factors of steatosis . If all known causes of fatty liver are excluded, the prevalence of steatosis in chronic hepatitis C remains elevated (about 40%), which is higher than that found in chronic hepatitis B (25–55%) and in the general population of Western countries (20–30%) . Such observations suggest that the hepatitis C virus (HCV) itself may induce steatosis. In patients with chronic hepatitis C, steatosis is usually mild or moderate. Severe steatosis, involving more than 60% of hepatocytes, is observed in less than 10% of the patients . Steatosis in chronic hepatitis C is predominantly macrovesicular and is located in the periportal area rather than in the centrilobular area. This is in contrast to what is observed in non-alcoholic fatty liver disease and alcoholic liver disease .

Cellular and molecular basis of fibrogenesis in NASH - Corrected Proof

2010-02-08

Fibrosis due to nonalcoholic steatohepatitis (NASH) develops primarily in the pericentral areas, where thin bundles of fibrotic tissue surround groups of hepatocytes and thicken the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The major cell type responsible for extracellular matrix deposition in this context is represented by activated hepatic stellate cells (HSCs) . The profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, particularly alcohol-mediated liver damage. Nonetheless, some specific molecular actions are related to the excess adiposity and fat-mediated liver damage.

Use of a standard gastroscope for colonoscopy at a general hospital in Venezuela: A prospective randomized trial - Corrected Proof

Jacobo Dib, Solangel Díaz, Andrés Ortiz, Natasha Bastardo — 2010-02-01

Abstract: Background and study aims: The use of an upper endoscope has been considered as a back-up method in case of incomplete caecal intubation. We compared caecal intubation rates between colonoscopic examinations done with a standard colonoscope and those in which a standard gastroscope was used, to determine if routine colonoscopies could be performed with a gastroscope if no colonoscope is available.Patients and methods: A prospective comparative study, analyzing continuous data was designed to evaluate the usefulness of a standard gastroscope in a group of outpatients with indication for colonoscopy in colorectal cancer screening. A total of 170 adult patients were randomly assigned to two similar study groups. All examinations were performed by a single endoscopist. Our primary end point was to achieve caecal intubation.Results: Successful caecal intubation was achieved in 162 patients that fulfilled our inclusion criteria, 83 patients in the colonoscope and 79 in the gastroscope group. Failure of caecal intubation was similar in male and female patients in both groups (p=0.34). Caecal intubation failure rates were similar in both study groups.Conclusions: We used the gastroscope as a first line method for routine colonoscopies and found no statistical difference between the colonoscope and gastroscope groups. If these results can be verified in larger multicenter studies, it may be possible in the future, to work with only one endoscope for both upper and lower digestive tract examinations in small centers, particularly in developing countries.

Antifibrotic agents emerging from traditional herbal medicine - Corrected Proof

Norifumi Kawada — 2010-01-20

Hepatic fibrogenesis is a complex and dynamic pathological process that is controlled by the synthesis and degradation of extracellular matrix materials, including fibril-forming collagens. The proliferation and apoptosis of fibroblastic cell populations in the liver participate in the process as well. Stellate cells comprise the hepatic sinusoidal wall and play multiple roles in the fibrotic process. Transformation of stellate cells from the vitamin A-storing to the ‘myofibroblastic’ phenotype closely correlates with hepatic fibrogenesis during chronic liver trauma. Molecular analyses of this phenotypic change of stellate cells, the so-called ‘activation’, have made great progress, in particular, in the field of intracellular signal transduction of transforming growth factor-β. TGF-β and platelet-derived growth factor-BB (PDGF-BB), as well as collagen gene expression. Using the information on stellate cell activation, therapeutic strategies against fibrosis in human liver disease are being developed.

Potential novel biomarkers for monitoring the fibrogenic process in liver - Corrected Proof

Axel M. Gressner, Mohamed Rizk, Chunfang Gao, Olav A. Gressner — 2010-01-18

Abstract: The clinical course of chronic liver diseases is significantly dependent on the progression rate of fibrosis, that is, the unstructured replacement of injured parenchyma by extracellular matrix. Fibrogenesis (i.e., the development of fibrosis) can be regarded as an unlimited wound-healing process, which is based on matrix synthesis in activated hepatic stellate cells, fibroblasts and, potentially, by hepatocytes and biliary epithelial cells converted to (myo-)fibroblasts. Blood biomarkers of fibrogenesis and fibrosis can be divided into class I and class II. Class I biomarkers are single tests, which are based on the pathophysiology of fibrosis, whereas class II biomarkers are mostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and follow-up of fibrosis. None of the presently available approach fulfils the criteria of an ideal test, but increased understanding of the pathogenesis of fibrosis offers additional ways for pathophysiologically well-based biomarkers. These include transforming growth factor (TGF)-β-driven marker proteins, bone-marrow-derived cells (fibrocytes) and cytokines, which govern pro- and anti-fibrotic activities. Proteomic and glycomic approaches of serum are under investigation to set up specific protein profiles in patients with liver fibrosis. These and other novel parameters will supplement liver biopsy/histology, high-resolution imaging analysis and elastography for the detection and monitoring of patients with liver fibrosis.

New developments in the treatment of chronic hepatitis B - Corrected Proof

Stephanos J. Hadziyannis — 2010-01-14

Effective treatment of chronic hepatitis B (CHB) is a rapidly evolving subject in medicine. It opened in the early 1990s when recombinant α-interferons, 2a (IFN-α2a) and α2b (IFN-α2b), became available. The treatment was revolutionised in the late 1990s with the introduction and approval of the first oral nucleoside analogue, lamivudine. During the last 5years, it has further expanded with the addition of newer compounds. The current defence against HBV includes two IFN-α preparations and four oral nucleos(t)ide analogues (NUCs), while many more drugs are expected to be licensed in the near future .