Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980-2019.

BACKGROUND: This cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980-2019. METHODS: Using oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model. RESULTS: Overall ASIR of oesophageal cancer was 10.51 (95% CI:  6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer.  Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly  (p < 0.005) declined in subsequent periods till 2015-19. CONCLUSIONS: A high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.

Modulation of Immune Cell Subsets by Hepatitis C Virus and Antiviral Therapy in Early Virological Response HCV Genotype 4-Infected Patients with Compensated Liver Disease.

BACKGROUND: Resolution of chronic hepatitis C virus (HCV) infection requires a complicated interaction between immune cell subsets. The effect of antiviral therapy on immune cell subsets remains to be defined. This study aimed to investigate the absolute count of certain immune cell subsets during therapy with pegylated interferon-α and ribavirin (PegIFN/RBV). MATERIALS AND METHODS: Sixty HCV genotype 4-infected patients with compensated liver disease were treated with PegIFN/RBV therapy for 52 weeks. Efficacy was measured by studying the early virological response (EVR) at post-therapy week 12. Absolute counts of mature T cells, T helper cells, T cytotoxic cells, activated T cells, natural killer cells, natural killer/T (NKT) cells, B cells, and T regulatory cells (Treg), and the ratio of T helper to T cytotoxic cells were longitudinally analyzed by flow cytometry throughout the treatment and follow-up course. RESULTS: Of the 60 genotype 4-infected subjects, 39 (65%) had EVR and 21 (35%) were non-EVR patients. In the first part of this study, there were significantly lower mean absolute count values of mature T, T cytotoxic, B, and NKT cells. Also, we detected statistically significantly lower mean values for the percentages of T cytotoxic, NKT, Treg, and activated T cells of HCV-infected patients at baseline values when compared with healthy subjects. After the initiation of PegIFN/RBV therapy, frequencies of T helper cells, activated T cells, Treg cells, B cells, and T helper:T cytotoxic ratio were found to be significantly lower in EVR patients than in non-EVR patients (p < 0.05). In contrast, frequencies of T cytotoxic and NKT cells were significantly increased in EVR patients when compared to non-EVR patients (p < 0.05). CONCLUSION: These results suggest a pattern of higher levels of T cytotoxic and NKT cells, and lower levels of T helper, activated T, Treg, and B cell populations in patients who respond favorably to PegIFN/RBV therapy.

What constitutes an Arabian Helicobacter pylori? Lessons from comparative genomics.

BACKGROUND: Helicobacter pylori, the human gastric pathogen, causes a variety of gastric diseases ranging from mild gastritis to gastric cancer. While the studies on H. pylori are dominated by those based on either East Asian or Western strains, information regarding H. pylori strains prevalent in the Middle East remains scarce. Therefore, we carried out whole-genome sequencing and comparative analysis of three H. pylori strains isolated from three native Arab, Kuwaiti patients. MATERIALS AND METHODS: H. pylori strains were sequenced using Illumina platform. The sequence reads were filtered and draft genomes were assembled and annotated. Various pathogenicity-associated regions and phages present within the genomes were identified. Phylogenetic analysis was carried out to determine the genetic relatedness of Kuwaiti strains to various lineages of H. pylori. The core genome content and virulence-related genes were analyzed to assess the pathogenic potential. RESULTS: The three genomes clustered along with HpEurope strains in the phylogenetic tree comprising various H. pylori lineages. A total of 1187 genes spread among various functional classes were identified in the core genome analysis. The three genomes possessed a complete cagPAI and also retained most of the known outer membrane proteins as well as virulence-related genes. The cagA gene in all three strains consisted of an AB-C type EPIYA motif. CONCLUSIONS: The comparative genomic analysis of Kuwaiti H. pylori strains revealed a European ancestry and a high pathogenic potential.

Endoscopic management of post-laparoscopic sleeve gastrectomy stenosis.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is becoming an increasingly popular form of bariatric surgery, accounting for more than 50% of these procedures performed in the USA. Given this popularity, more is being understood about the complications associated with LSG, which, though uncommon, include the formation of strictures and stenosis. The purpose of this study is to establish a safe and effective protocol for the treatment of stenosis post-LSG using endoscopic balloon dilatation. MATERIALS AND METHODS: This is a prospective review of 26 patients who had undergone LSG in Kuwait, followed by sleeve gastrectomy stenosis (SGS) and were then referred to Amiri Hospital for endoscopic balloon dilatation from October 2008 up to June 2016. RESULTS: A total of 26 patients (four males; 22 females) presented with symptoms of stenosis post-LSG during the study period. The mean age of the patients was 34.6 ± 10.8 years. The mean body mass index at the time of surgery was 43 ± 1.6 kg/m2. The median interval from the initial LSG surgery was 95 days. Nine patients had an early presentation (≤3 months from surgery), while 17 presented late (>3 months). The patients were followed for a mean duration of 156 ± 20 days from the last endoscopic balloon dilatation. A total of 23 (88.5%) patients had complete resolution of their symptoms. Adverse events were observed in one patients, who was removed from the study. CONCLUSIONS: Gastric stenosis is a rare but potentially serious complication of LSG. Serial dilatation of SGS employing endoscopic balloons is a safe method of treatment, with high efficacy rates. This new method may offer a less invasive alternative to surgical revision. However, if endoscopic treatment fails, surgery is necessary.

Demography and clinical course of ulcerative colitis in Arabs - a study based on the Montreal classification.

OBJECTIVE: Ulcerative colitis (UC) is generally considered a disease of the Caucasian populations in developed countries, but its incidence is increasing rapidly in many developing countries, including the Middle East. The objective of this study was to determine the clinical epidemiology of UC in Arabs. MATERIAL AND METHODS: This cross-sectional medical record-based descriptive study collected sociodemographic and clinical information on 182 Arab patients with UC in Kuwait. Age at diagnosis, extent and severity of disease were determined according to the Montreal classification. results: Among the 182 patients, 91 (50.0%) were males. The median age at diagnosis was 28.5 years. Family history of UC was reported by 26 (14.3%) patients. The extent of the disease was limited to the rectum in 34 (18.7%) patients, left sided in 67 (36.8%) and pan colitis in 81 (44.5%). At the time of inclusion in the study, 127 (69.8%) patients were in clinical remission, 53 (29.1%) had mild-to-moderate disease and 2 (1.1%) had severe colitis. Younger age at diagnosis and non-smoking were associated with more extensive colitis. The majority of patients were treated with mesalamine, steroids and immunomodulators, while biologic therapy and surgery were needed in 5% and 4% of the patients, respectively. CONCLUSIONS: UC presents more commonly at younger age among Arabs in Kuwait. Extensive disease at presentation is associated with younger age at diagnosis and absence of tobacco smoking. There also appears to be less need for surgery and biologic therapy for the disease in this population.

Pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C virus genotype 4 infection in patients with normal serum ALT.

BACKGROUND: Approximately one-third of patients with chronic hepatitis C virus infection have persistently normal liver enzymes reflected by a normal serum alanine transaminase (ALT). Data with regards the efficacy and safety of treatment in patients chronically infected with Hepatitis C virus genotype 4 and normal serum ALT are limited. AIM: To evaluate the efficacy and safety of peginterferon alfa-2b plus ribavirin combination therapy in this population. MATERIAL AND METHODS: Twenty-two patients with chronic hepatitis C virus genotype 4 infection were enrolled in an open-labeled, uncontrolled pilot study. All patients had biopsy proven chronic hepatitis and persistently normal serum ALT levels. Patients were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 µg/kg body weight once per week plus oral ribavirin (15 mg/kg/day) for 48 weeks. Patients were followed for 24 weeks post-treatment. RESULTS: Sixteen patients out of twenty two completed the study (9 [40.9%] females, mean age 43.8 years). The ALT level were normal in all patients, with a mean of 38.6 U/L. Sustained viral response was achieved in 13 patients (59%), 4 patients (18.1%) were non-responders and 2 patients (9%) relapsed while 1 patient had a viral breakthrough during treatment. Two patients (9%) discontinued the treatment because of adverse events. CONCLUSIONS: Combination therapy of pegylated interferon-alpha2b and ribavirin is safe and resulted in a sustained virological response in a significant number of patients with chronic Hepatitis C, genotype 4, and persistently normal serum ALT.

Mechanism of regulation of Na-H exchanger in inflammatory bowel disease: role of TLR-4 signaling mechanism.

OBJECTIVE: We investigated the role of toll-like receptor-4 (TLR-4) signal transduction in the regulation of Na-H exchanger-1 isoform (NHE-1) in ulcerative colitis (UC). METHODS: Colonic biopsies from control and UC patients were selected from four groups: controls (group 1), untreated UC patients (group 2), UC patients treated with 5'-aminosalicylic acid (5'-ASA) plus steroid (group 3), and UC patients treated with 5'-ASA plus azathioprine (AZA) (group 4). Patients presenting with abdominal pain (n = 13) and a normal colon on endoscopy served as controls. NHE-1, TLR-4, MyD88, NFkB and actin protein levels were estimated using Western blot analysis and sodium pump activity (PNPase) by a spectrophotometeric method. Myeloperoxidase (MPO) activity and histologic evaluation confirmed inflammation. RESULTS: PNPase activity decreased significantly (P < 0.05) in the untreated UC patients as compared to the controls or treated UC groups 3 and 4. There was a significant decrease of NHE-1 and a significant increase (P < 0.05) of TLR-4, MyD88 and NFkB protein levels in the untreated UC or 5'-ASA plus steroid treated UC patients as compared to the controls. NHE-1, TLR-4, MyD88 and NFkB protein levels were not significantly different in 5'-ASA plus AZA treated biopsies as compared to controls. The level of actin remained unaltered. Inflammatory cells' infiltration and MPO activity increased significantly in the untreated UC, but was significantly lower in the treated UC groups 3 and 4 (P < 0.05). CONCLUSIONS: These findings suggest that NHE-1 in UC is regulated by NFkB induced through TLR-4 and MyD88 signaling mechanism. These findings identify TLR-4 as a putative therapeutic target for IBD.

Modulation of Production of Th1/Th2 Cytokines in Peripheral Blood Mononuclear Cells and Neutrophils by Hepatitis C Virus Infection in Chronically Infected Patients.

This study investigated the influence of Hepatitis C virus (HCV) infection on the cytokine production profiles of the peripheral blood monoculear cells (PBMC) and neutrophils in chronically naïve HCV-infected patients. Seventy-five genotype-4 naïve HCV-infected patients (HCV+) and healthy subjects (HCV-) were enrolled. The neutrophils and the PBMC were separated by density gradient sedimentation and stimulated with a mitogen. The culture supernatants were evaluated for levels of IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, and TNF-α using anti-cytokine antibody MACSPlex capture beads. The PBMC cytokine profiles of HCV+ patients showed significantly lower mean values for IFN-γ, IL-2, IL-6, IL-9, and IL-10 (p < 0.0001) as compared to HCV- subjects. In contrast, HCV+ patients showed higher mean levels of PBMC cytokine values for IL-5 and TNF-α (p < 0.0001). As for neutrophils, HCV+ patients showed significantly lower mean levels of IFN-α, IFN-γ, IL-2, IL-4, IL-6, IL-9, and IL-10 (p < 0.0001). In contrast, the neutrophils from HCV+ patients showed higher mean levels of IL-5, IL-12, and TNF-α (p < 0.0001). Th1-Th2 cytokine ratios suggested a lower Th1 bias in HCV+ subjects as compared to HCV- subjects. Our results suggest that chronic HCV infection brings about an immunomodulatory effect not only on neutrophils, but also to a lower extent on PBMCs.

Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease.

Background: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait. Methods: Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the "CT" or "TT" genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22-0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19-5.97). Conclusions: In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait.

Prevalence of Helicobacter pylori infection among new outpatients with dyspepsia in Kuwait.

BACKGROUND: Testing and treatment for Helicobacter pylori has become widely accepted as the approach of choice for patients with chronic dyspepsia but no alarming features. We evaluated H. pylori status among outpatients with uninvestigated dyspepsia in Kuwait. METHODS: A prospectively collected database for 1035 patients who had undergone 13C-urea breath tests (UBT) for various indications was reviewed for the period from October 2007 to July 2009. The status of H. pylori in dyspeptic patients was determined by UBT. RESULTS: Among the 362 patients who had undergone UBT for uninvestigated dyspepsia, 49.7% were positive for H. pylori (95% CI = 44%-55%) and the percentage increased with age (35.8% at 20-29 years, 95% CI = 25.4% - 47.2%; 59.3% at 30-39 years, 95% CI = 48.5% - 69.5%) (P = 0.013). The prevalence of H. pylori was 42.6% among Kuwaitis (95% CI = 35%-50%) and 57.6% (95% CI = 49.8%-65%) among expatriates (p = 0.004). The prevalence among males was 51.3%, while in females it was 48.6%. CONCLUSIONS: Almost half of the patients with dyspeptic symptoms in Kuwait were positive for H. pylori, though the prevalence varied with age and was higher among expatriates. The American Gastroenterology Association guidelines recommending testing and treatment for H. pylori for patients with uninvestigated dyspepsia should be endorsed in Kuwait.

Dental x-rays and the risk of thyroid cancer: a case-control study.

UNLABELLED: The thyroid gland is highly susceptible to radiation carcinogenesis and exposure to high-dose ionising radiation is the only established cause of thyroid cancer. Dental radiography, a common source of low-dose diagnostic radiation exposure in the general population, is often overlooked as a radiation hazard to the gland and may be associated with the risk of thyroid cancer. An increased risk of thyroid cancer has been reported in dentists, dental assistants, and x-ray workers; and exposure to dental x-rays has been associated with an increased risk of meningiomas and salivary tumours. METHODS: To examine whether exposure to dental x-rays was associated with the risk of thyroid cancer, we conducted a population-based case-control interview study among 313 patients with thyroid cancer and a similar number of individually matched (year of birth +/- three years, gender, nationality, district of residence) control subjects in Kuwait. RESULTS: Conditional logistic regression analysis, adjusted for other upper-body x-rays, showed that exposure to dental x-rays was significantly associated with an increased risk of thyroid cancer (odds ratio = 2.1, 95% confidence interval: 1.4, 3.1) (p=0.001) with a dose-response pattern (p for trend <0.0001). The association did not vary appreciably by age, gender, nationality, level of education, or parity. DISCUSSION: These findings, based on self-report by cases/controls, provide some support to the hypothesis that exposure to dental x-rays, particularly multiple exposures, may be associated with an increased risk of thyroid cancer; and warrant further study in settings where historical dental x-ray records may be available.

Efficacy of standard triple therapy in the treatment of Helicobacter pylori infection: experience from Kuwait.

INTRODUCTION: Recent studies suggest that the initial treatment success rates for H. pylori infection are falling below 80% in many parts of the world. AIM: The aim of this study was to evaluate the efficacy of standard triple therapy in the treatment of H. pylori infection in Kuwait. METHODS: Consecutive H. pylori positive patients were enrolled in the study to receive clarithromycin, amoxicillin and omeprazole for 10 days. H. pylori status was checked with 13C urea breath test 6 weeks after the end of therapy. Endoscopic findings was recorded in all patients. RESULTS: One hundred forty-one patients (82 male and 59 females; mean age 41.8 years) were enrolled in the study. A total of seven patients were excluded from the per protocol analysis. The eradication rates in intention to treat (ITT) and per protocol (PP) were 72.3% (95% CI 64.2-79.5%) and 76.1% (95% CI 68-83%), respectively. The main endoscopic findings were normal in 47.5% and gastritis in 37.6%. CONCLUSION: The efficacy of the current standard triple therapy for H. pylori eradication in our community is suboptimal. Confirmation for H. pylori eradication with noninvasive tests is recommended, especially in high-risk patients. New antimicrobial regimens for H. pylori eradication are considered necessary.

Endoscopic internal drainage by double pigtail stents in the management of laparoscopic sleeve gastrectomy leaks.

BACKGROUND: Leaks and fistulas after laparoscopic sleeve gastrectomy (SG) are major adverse events of bariatric surgery. Endoscopic management of post-SG leaks has evolved from closure with covered self-expanding metallic stents to endoscopic internal drainage (EID). OBJECTIVE: To report our experience with the management of post-SG leaks treated with EID, either as primary therapy or after failure of closure therapy with self-expanding metallic stents. SETTING: Single-center observational study. METHODS: A retrospective study of 20 patients treated for post-SG leaks with EID by deployment of double pigtail stents across the leak orifice, positioning one end inside the collection and the other end in the lumen of the stomach. RESULTS: There were 13 (65%) males and 7 (35%) females with a mean age of 34.2 ± 11.6 years. EID was performed after a mean 62 days after SG. Three patients had gastrobronchial fistula. Seventeen (85%) patients had failed some form of prior therapy for the leak. The mean duration of EID was 83 days and 17 (85%) patients had complete healing of the leak with a mean follow-up of 16 months. There were 2 (10%) adverse events and no mortalities. The success of EID in healing post-SG leak was significantly associated with the absence of a gastrobronchial fistula (P < .05). CONCLUSIONS: EID is an effective and safe endoscopic treatment of leaks after SG and is well tolerated. It allows early feeding and has fewer adverse events than other techniques. The presence of a gastrobronchial fistula is associated with higher failure rates. Long-term follow-up confirms a good outcome with no mortality.

Suppression of Na+/H+ exchanger isoform-3 in human inflammatory bowel disease: lack of reversal by 5'-aminosalicylate treatment.

OBJECTIVE: Na+/H+ exchanger isoform 3 (NHE-3) is responsible for net uptake of NaCl and water from the gastrointestinal (GI) tract. However, its status in human inflammatory bowel diseases (IBDs) such as ulcerative colitis(UC) and Crohn's disease (CD) remains poorly understood. The aim of this study was to investigate the underlying mechanism of NHE-3 isoform expression and its modulation by 5'-aminosalicylate in human CD and UC. MATERIAL AND METHODS: Subjects were divided into three groups: 1) controls; 2) untreated/new IBD cases (n = 13) and 3) 5'-aminosalicylate-treated IBD patients (n = 13). Subjects presenting with abdominal pain but with endoscopically normal colons served as normal controls. Inflammation was confirmed by the level of myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentrations and by histologic evaluation. Expressions of NHE-3 protein and mRNA, sodium pump activity and IL-1beta and TNF-alpha mRNA were estimated in the colonic biopsies using ECL-Western blot analysis,reverse transcription-polymerase chain reaction (RT-PCR) and enzyme assays. RESULTS: The level of NHE-3 protein and sodium pump activity was reduced (p < 0.05) in both the untreated and treated CD and UC patients. NHE-3 mRNA was reduced only in CD patients but not in those with UC. The treatment reversed the symptoms, but levels of MPO activity, MDA concentration, IL-1beta, TNF-alpha and infiltration of inflammatory cells remained high with the exception of IL-1beta mRNA in the treated patients. CONCLUSIONS: NHE-3 suppression is regulated differentially in CD and UC, which together with suppression of sodium pump activity will reduce NaCl and water uptake from the colonic lumen. These findings suggest a role of TNF-a in the regulation of NHE-3 expression in IBD.

A Complication of an Endoscopic Pigtail Stent Migration into the Cavity during Deployment as a Treatment for Gastric Leak.

Gastric leak following gastrointestinal surgery is the most dreadful complication, which implies long hospital stay, morbidities, and not irrelevant mortalities. There is no standard recommendation for treating postlaparoscopic sleeve gastrectomy leak, which makes its management challenging. Endoscopic internal drainage by double-pigtail drains currently became the recommended approach. Complications to this approach include bleeding, ulceration at the tip of the double-pigtail stent, and uncommon migration. Here, we report our experience with drain displacement into the cavity while deployment in a patient who experienced gastric leakage after undergoing sleeve gastrectomy.

Appropriateness of indication and diagnostic yield of colonoscopy: first report based on the 2000 guidelines of the American Society for Gastrointestinal Endoscopy.

AIM: To assess the appropriateness of referrals and to determine the diagnostic yield of colonoscopy according to the 2000 guidelines of the American Society for Gastrointestinal Endoscopy (ASGE). METHODS: A total of 736 consecutive patients (415 males, 321 females; mean age 43.6+/-16.6 years) undergoing colonoscopy during October 2001-March 2002 were prospectively enrolled in the study. The 2000 ASGE guidelines were used to assess the appropriateness of the indications for the procedure. Diagnostic yield was defined as the ratio between significant findings detected on colonoscopy and the total number of procedures performed for that indication. RESULTS: The large majority (64%) of patients had colonoscopy for an indication that was considered "generally indicated", it was "generally not indicated" for 20%, and it was "not listed" for 16% in the guidelines. The diagnostic yield of colonoscopy was highest for the "generally indicated" (38%) followed by "not listed" (13%) and "generally not indicated" (5%) categories. In the multivariable analysis, the diagnostic yield was independently associated with the appropriateness of indication that was "generally indicated" (odds ratio=12.3) and referrals by gastroenterologist (odds ratio =1.9). CONCLUSION: There is a high likelihood of inappropriate referrals for colonoscopy in an open-access endoscopy system. The diagnostic yield of the procedure is dependent on the appropriateness of indication and referring physician's specialty. Certain indications "not listed" in the guidelines have an intermediate diagnostic yield and further studies are required to evaluate whether they should be included in future revisions of the ASGE guidelines.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.

BACKGROUND: A significant proportion of hepatitis C patients treated with unmodified interferon plus ribavirin fail to respond. The optimal therapy for these patients has not been established yet. The objective of this study was to assess the efficacy and safety of peginterferon plus ribavirin with or without amantidine in such patients. METHODS: In this open-label, prospective controlled trial, a total of 63 patients were randomly divided into groups A and B with a ratio of 1:2. Group A (21 patients) received weekly peginterferon alpha-2b, 1.5 microg/kg concomitantly with ribavirin 1000-1200mg per day. Group B (42 patients) received peginterferon and ribavirin as in group A, plus amantadine [corrected] 200 mg per day. RESULTS: At the completion of treatment, serum levels of hepatitis C virus RNA were undetectable in 14% and 12% of patients in groups A and B, respectively (P=NS). Hepatitis C virus RNA remained undetectable 24 weeks after the end of treatment in one patient (5%) in group A and three patients (7%) in group B (P=NS). Sustained viral clearance was associated with sustained normalization of serum alanine aminotransferase level. Both drug regimens had similar side effect profiles. CONCLUSION: Peginterferon plus ribavirin therapy with or without amantadine [corrected] is associated with a low sustained virological response in patients who failed interferon and ribavirin combination therapy.

CLIP score as a prognostic indicator for hepatocellular carcinoma: experience with patients in the Middle East.

OBJECTIVE: To assess the prognostic ability of the Cancer of the Liver Italian Programme (CLIP) score and compare it with the Okuda system in patients with hepatocellular carcinoma from the Middle East, where the majority (70%) present with intermediate or advanced stages of the disease and do not receive any tumour-specific treatment. METHODS: The medical records of 145 patients (113 males; mean age, 58.8 +/- 12.2 years) diagnosed with hepatocellular carcinoma over a 6-year period were reviewed and the disease was staged according to the CLIP and Okuda systems. The survival was compared by Kaplan-Meier curves and Cox regression analysis. RESULTS: The overall median survival of patients with hepatocellular carcinoma was 8.3 months (95% confidence interval, 6.6-9.4). The median survivals for CLIP score 0, 1, 2, 3 and 4-6 were 35, 29, 9, 6, and 2 months, respectively; for Okuda stages I, II and III, they were 24, 9 and 4 months, respectively. The CLIP system was judged to be statistically more efficient and consistent than the Okuda in predicting survival in the Cox proportional hazard model. CONCLUSIONS: These data from patients with hepatocellular carcinoma in the Middle East suggest that the CLIP score is more reliable than the Okuda system in predicting survival and can be used efficiently to determine prognosis in patients who present with intermediate or late stage of the disease.

Role of Na+/H+ exchanger isoform-1 in human inflammatory bowel disease.

BACKGROUND: Na+/H+ exchanger (NHE) is responsible for a net uptake of sodium chloride and water from the gastrointestinal tract and maintains electrolyte and water homeostasis. However, its status in human inflammatory bowel disease such as ulcerative colitis (UC) and Crohn's disease (CD) remains poorly understood. OBJECTIVES: To investigate the role of NHE-1 isoform in human CD and UC. METHODS: Expression of NHE-1 protein and messenger ribonucleic acid and sodium pump activity were examined in the colonic biopsy samples taken from UC (n=11) and CD (n=13) patients using enhanced chemiluminescence-Western blot analysis, reverse transcription polymerase chain reaction and spectrophotometry. Subjects presenting with abdominal pain and endoscopically normal colon served as normal controls (n=11). Myeloperoxidase (MPO) activity and histology were performed to confirm tissue inflammation. RESULTS: MPO activity increased significantly (P<0.05) in both UC and CD patients compared with the normal controls. Parallel to MPO activity profile, there was also a significantly higher infiltration of inflammatory cells in both cases. P-nitrophenylphosphatase activity, a marker of the sodium pump, remained unchanged in CD but increased significantly (P<0.05) in UC compared with the normal controls. On the contrary, the level of NHE-1 protein and messenger ribonucleic acid was significantly decreased (P<0.05) in both cases, whereas the internal control, a-actin remained unaltered. CONCLUSIONS: These findings demonstrate a transcriptionally regulated suppression of NHE-1 in both UC and CD. This NHE-1 suppression may reduce an uptake of sodium chloride and water from the inflamed colonic lumen and thus contribute to diarrhea and neuromuscular alterations in these conditions.