Fuad Hasan

Sampling variability on percutaneous liver biopsy in patients with chronic hepatitis C virus infection.

Background: Sampling variability on liver biopsy has been demonstrated in a variety of liver diseases. The objective of this study was to determine whether sampling variability exists on percutaneous liver biopsy in patients with chronic HCV infection. Methods: Two separate tissue samples were obtained from the right lobe of the liver, through a single skin puncture, in 29 patients (22 M, mean age 43.4 ± 8.1 years) with chronic HCV infection. The biopsies were assessed using a descriptive histological reporting system and Knodells Histological Activity Index (HAI) and compared for differences in necroinflammatory activity (grade) and fibrosis (stage). Results: Thirteen (44.8%) patients had a difference of ≥1 grade between the 2 biopsies on the descriptive system and 13 differed by ≥1 stage. On the HAI, 20 (69.0%) patients had a difference of ≥2 in the necroinflammatory activity score and 10 (34.5%) had a difference of ≥4; whereas, 11 (38.0%) patients had a difference of ≥1 in the fibrosis score and 6 (20.7%) had a difference of ≥2. The mean difference between the two sets of biopsies was 2.4 ±2.1 (range 0–7) for the necroinflammatory activity and 0.6 ±0.9 (range 0–3) for fibrosis. Spearmans correlation coefficient (r) was moderate for both necroinflammatory activity (r = 0.53, P < 0.01) and fibrosis (r = 0.62, P < 0.0001). Conclusions: Sampling variability exists on percutaneous liver biopsy in patients with chronic HCV infection and should be taken into consideration when decisions regarding prognosis and therapy are made based on biopsy, and when defining histological response to antiviral regimens.

Peginterferon Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C Genotype 4

BACKGROUND:The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited.OBJECTIVE:To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4.METHODS:Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 ± 9 years, and mean weight 74 ± 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 × 106 copies/ml (8.4 × 105 iu/ml) and median was 2.15 × 106 copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000–1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis.RESULTS:End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA ≥2 × 106 SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 × 106 (p = 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively.CONCLUSION:Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.

Ulcerative Colitis in Kuwait: A Review of 90 Cases

Background: Chronic ulcerative colitis is a disease of unknown etiology. Its incidence is on the rise in various developing countries as has been reported in studies from South-East Asia and the Middle East. There seems to be significant differences in the pattern and the clinical course of this disease in our patient population. The aim of our study is to assess the incidence and the clinical course of the disease in Kuwait. Methods: This is a retrospective study of cases identified over a period of 14 years (1985–1999). Three hundred forty-six patients were identified to have chronic ulcerative colitis. Ninety patients were interviewed for this study. Results: Chronic ulcerative colitis is being identified with increasing frequency. Our local incidence was 2.8 per 100,000 persons per year. The disease was seen in both sexes with equal frequency. It peaks at the third decade of life, with no second peak observed in the sixth decade. The disease was of mild to moderate severity in 93% of the cases. The distribution of the disease in the colon showed pancolitis in 45%, left-sided colitis in 14%, proctosigmoiditis in 21% and proctitis in 20%. Arthritis and arthralgia were the most frequent extraintestinal manifestation seen in 31%. Perianal disease, although rare in ulcerative colitis, was seen in 8%. Of interest is the fact that over 14 years of follow-up, none of our patients developed high-grade dysplasia or colorectal cancer. Four patients required total colectomy mainly due to failure of medical therapy. Conclusions: Chronic ulcerative colitis is occurring with increasing frequency similar to that seen in Western countries. The disease observed in our patient population was of mild to moderate severity, with fewer complications than reported in Western countries. It peaks in the third decade with no second peak. None of our patients developed high-grade dysplasia or colorectal carcinoma.

Diagnosis of Helicobacter pylori: improving the sensitivity of CLOtest by increasing the number of gastric antral biopsies.

Background and Goal The rapid urease CLOtest is commonly used during endoscopy to diagnose the presence of Helicobacter pylori. The aim of this study was to determine whether the sensitivity of the CLOtest can be improved by increasing the number of gastric antral biopsies from 1 to 4. Methods The study included 100 adult patients who were referred for upper gastrointestinal endoscopy and tested positive for H. pylori infection on 13C urea breath test (“gold standard”). These 100 patients were then randomly divided into 4 equal groups (groups 1 to 4), and underwent an upper gastrointestinal endoscopy. Patients in group 1 had 1 gastric antral biopsy during endoscopy, whereas those in groups 2, 3, and 4 had 2, 3, and 4 biopsies, respectively. The biopsies were placed in the rapid urease CLOtests, which were incubated at room temperature for up to 24 hours, and read for positive results at 1, 6, and 24 hours. Results About half of the patients (52%) had a positive CLOtest in group 1, compared to 68% in group 2, 76% in group 3, and 96% in group 4 (group 1 vs. 4 P<0.01). After 1 hour of incubation 96% of the patients in group 4 had a positive CLOtest, compared to 40% in group 3, 12% in group 2, and 4% in group 1. Conclusions Increasing the number of gastric antral biopsies from 1 to 4 significantly improves the sensitivity of the CLOtest, eliminates sampling error, and hastens the time needed by the test to become positive for the diagnosis of H. pylori infection.

Transjugular Liver Biopsy in Patients with EndStage Renal Disease

PURPOSE To assess the efficacy and safety of transjugular liver biopsy (TJLB) in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis treatment. MATERIALS AND METHODS Forty-six consecutive patients with liver disease who were undergoing hemodialysis were included in this study. An 18-gauge Tru-cut transjugular needle with a 20-mm throw was used to obtain liver tissue. All procedures were performed under fluoroscopic guidance. A single pathologist reviewed the biopsy specimens and assessed the size of fragments, number of portal tracts, and adequacy of the specimens for histologic diagnosis. All complications were recorded. The results were compared with the outcomes of percutaneous liver biopsy carried out at our institution in 32 patients with ESRD. RESULTS TJLB and percutaneous biopsy techniques yielded adequate specimens for histologic diagnosis in all patients. The mean length of the largest fragments of tissue obtained via the transjugular and percutaneous routes were 16 mm +/- 4 and 14 mm +/- 3, respectively (P = NS). There were no major complications among patients who underwent TJLB. Percutaneous liver biopsy was complicated by hemorrhage in four of 32 patients (12%), three of whom required blood transfusion. CONCLUSION TJLB is an effective and safe technique to obtain liver tissue in patients with ESRD and is associated with a lower complication rate than percutaneous liver biopsy.

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 Crohns 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-1β and TNF-α 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-1β, TNF-α and infiltration of inflammatory cells remained high with the exception of IL-1β 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-α in the regulation of NHE-3 expression in IBD.

Comparative evaluation of INNO-LiPA HBV assay, direct DNA sequencing and subtractive PCR-RFLP for genotyping of clinical HBV isolates.

Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to antiviral therapy in HBV-infected patients. Several methods have been developed for rapid genotyping of HBV strains. However, some of these methods may not be suitable for developing countries. The performance of INNO-LiPA HBV Genotyping assay (LiPA), direct DNA sequencing and subtractive PCR-RFLP of genotype-specific HBV genome regions were evaluated for accurately determining the HBV genotypes by analyzing sera (n = 80) samples from chronic HBV patients. Both, LiPA and DNA sequencing identified 63, 4 and 13 HBV strains as belonging to genotype D, genotype A and mixed genotype A and D, respectively. On the contrary, the PCR-RFLP-based method correctly identified all 4 genotype A but only 56 of 63 genotype D strains. Seven genotype D strains yielded indeterminate results. DNA sequence comparisons showed that a single nucleotide change in the target region generated an additional restriction site for Nla IV that compromised the accuracy of this method. Furthermore, all the mixed genotype A and D strains were identified only as genotype A strains. The data show that the PCR-RFLP-based method incorrectly identified some genotype D strains and failed to identify mixed genotype infections while LiPA and DNA sequencing yielded accurate results.

Interferon-Alpha in Combination with Ribavirin for the Treatment of Chronic Hepatitis C in Patients with Persistently Normal Aminotransferase Levels

Background and Aims: A substantial proportion of patients with chronic hepatitis C virus infection have persistently normal serum transaminase levels. The aim of this study was to assess the efficacy and safety of interferon plus ribavirin combination therapy in this population. Methods: In this prospective open trial 152 patients with biopsy-proven chronic hepatitis C were enrolled, 32 of whom had persistently normal alanine aminotransferase levels (group A). The remaining 120 patients served as a comparison (group B). Patients were treated for 12 months with 4.5 million units of interferon-α2a thrice weekly in combination with ribavirin 1,000 or 1,200 mg daily. They were followed up for at least 6 months after therapy. Serum hepatitis C RNA was detected by polymerase chain reaction and quantified by a branched DNA assay. Results: At the end of treatment, 12 (37.5%) and 48 patients (40%) were negative for HCV-RNA in groups A and B, respectively (p = 0.33). After 24 weeks of follow-up, 9 patients (28%) from group A and 36 patients (30%) from group B were still HCV-RNA negative (p = 0.4). Treatment was well tolerated by both groups. There were no alanine transferase elevations among group A patients during therapy. Conclusion: Interferon-ribavirin combination therapy was safe and induced a sustained virologic response in a significant proportion of patients with chronic hepatitis C and repeatedly normal serum transaminase levels.

Dyspepsia and Helicobacter pylori infection: Analysis of 200 Kuwaiti patients referred for endoscopy.

BACKGROUND Dyspepsia is a very common symptom, and is the reason for most referrals for esophagogastroduodenoscopy (EGD). Peptic ulcer disease (PUD), gastroesophageal reflux and gastric cancer account for a minority of such patients. However, the majority have no significant endoscopic abnormalities (non-ulcer dyspepsia). Recently, infection with Helicobacter pylori (HP) has been implicated in the pathogenesis of PUD and gastric cancer. Since HP can be diagnosed by noninvasive techniques, it has been suggested that endoscopy should be restricted to HP-positive patients who do not respond to empirical therapy with antimicrobials. The aim of this study was to establish the prevalence of HP among Kuwaiti dyspeptic patients referred for endoscopy and to determine whether demographic and clinical screening, or the presence of HP, can help distinguish groups of patients with significant gastroduodenal pathology from those with non-ulcer dyspepsia. PATIENTS AND METHODS Two hundred randomly selected Kuwaiti patients referred for endoscopy were evaluated prospectively. A detailed personal interview was conducted to establish the demographic and clinical profile of each patient and a diagnostic EGD was performed after the interview. Finally, antral mucosal biopsies were taken to determine the presence of HP. The pre-coded data were analyzed. RESULTS The main endoscopic findings were normal (32%), non-erosive antral gastritis (26%), duodenitis (17.5%), duodenal ulcer (11.5%), deformed bulb (4%), esophagitis (7%), and erosive gastritis (2%). The demographic and clinical characteristics of patients did not correlate with endoscopic findings. The overall prevalence of HP infection was 88.5%. There were no statistically significant differences in the prevalence of HP among patients with various endoscopic findings. CONCLUSION HP infection is common in Kuwaiti dyspeptic patients referred for endoscopy, irrespective of their demographic and clinical features or the underlying cause of dyspepsia. Noninvasive methods to detect HP are not valid alternatives to endoscopy in the work-up of dyspeptic patients.

Clinical epidemiology of Crohn's disease in Arabs based on the Montreal classification

Background: There has been a remarkable increase in the incidence of Crohns disease (CD) among Arabs in recent years. We conducted this study to determine the clinical epidemiology of CD in Kuwait. Methods: Sociodemographic and clinical information was collected for a continuous series of 206 Arab patients with CD and age at diagnosis and location and behavior of disease was determined according to the Montreal Classification. Results: Among the 206 patients, 100 (48.5%) were males and 106 (51.5%) females. The mean age at diagnosis (±SD) was 21.9 ± 10 years. Family history of CD was reported by 39 (18.9%) patients. The disease was limited to the ileum in 115 (55.8%) patients, whereas in 28 (13.6%) it involved the colon and in 63 (30.6%) it involved both the ileum and colon. The behavior of the disease was nonstricturing, nonpenetrating in 146 (70.9%) patients, whereas 49 (23.8%) had stricturing and 11 (5.3%) penetrating disease. Perianal disease was present in 41 (19.9%) patients. In the multivariate analysis, the use of biologic therapy and duration of the disease for ≥6 years were significantly associated with the presence of perianal disease, and the need for surgery was significantly associated with stricturing and penetrating disease behavior. Conclusions: CD among Arabs is equally common in males and females, presents at a relatively younger age, and in about half of the patients is limited to the small bowel. These features may indicate an underlying genetic predisposition for the disease in this population, which needs further investigation. (Inflamm Bowel Dis 2012;)