Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Systematic review and meta-analysis: full- vs. half-dose anti-microbials in clarithromycin-based regimens for Helicobacter pylori eradication.

BACKGROUND: Half-dose regimens may be equally effective but associated with diminished adverse events (AE) than standard-dose regimens. AIM: To assess efficacy and safety of full- vs. half-dose clarithromycin in the treatment of H. pylori. METHODS: Medline, EMBASE and PubMed databases were searched for randomised controlled trials (RCTs) that meet eligibility criteria. Only parallel group RCTs with ≥ 2 arms were eligible. Studies comparing triple, quadruple or sequential therapy for 7-14 days were selected. Regimens had to contain the same drug combination, differing only in dosage; the comparison of full- vs. half-dose clarithromycin was required, regardless if other drugs were dose-reduced or not. Data extraction was performed for primary outcome [eradication by intent-to-treat (ITT) and per-protocol (PP) analyses] and secondary outcome (AE). RESULTS: A total of 1622 articles were identified, of which 19 studies were eligible. Overall, eradication was achieved in 82.5% of half-dose (n = 2115) vs. 83.4% of full-dose recipients (n = 2109) on ITT (87.1% vs. 88.4% on PP respectively). Pooled relative risk in the half- vs. full-dose regimen was 0.98 (95% CI: 0.95-1.02) on ITT and 0.99 (95% CI: 0.97-1.01) on PP by the random effects model. Heterogeneity was significant (chi-squared statistic P = 0.05, I(2) = 37%). AE were reported in 29.3% of half- vs. 44.0% of full-dose recipients [pooled RR 0.67 (95% CI: 0.60-0.75)]. Pre-planned subgroup analyses of dose modification, sample size, study origin and treatment duration, as well as sensitivity analysis showed no significant differences between arms. CONCLUSION: A half-dose clarithromycin-based regimen is equally effective yet better tolerated than its full-dose counterpart in the treatment of H. pylori.

KIR genotype distribution among symptomatic patients with and without Helicobacter pylori infection: is there any role for the B haplotype?

UNLABELLED: Contact of peripheral blood lymphocytes with Helicobacter pylori was proved to induce non- major histocompatibility complex-restricted cytotoxicity and natural killer cells are thought to play an important role in the immunity against H. pylori. AIMS: In this research, we investigated any possible association between killer immunoglobulin-like receptors (KIR) genotypes and H. pylori infection. METHODS: KIR genotype was analysed in 101 Lebanese symptomatic patients (51 H. pylori positive and 50 H. pylori-negative) using the KIR Genotyping SSP kit. RESULTS: Among the H. pylori-positive patients, the AA, AB and BB genotypical frequencies were, respectively, 43.14%, 41.18% and 15.68% with an A:B ratio of 1.76:1. The AA, AB and BB genotypes frequencies for H. pylori-negative individuals were 18%, 62% and 20%, respectively, with an A:B ratio of 0.96:1. No significant difference between patients and controls was detected. CONCLUSIONS: We noticed a reduced distribution of A haplotype among the 'H. pylori-negative' patients as compared with the "H. pylori-positive" group. This is the first study in the international literature that targets the correlation between KIR genotypes and H. pylori.

A randomized single-blind trial of standard diet versus fiber-free diet with polyethylene glycol electrolyte solution for colonoscopy preparation.

BACKGROUND AND STUDY AIMS: Colonoscopy preparation usually involves the intake of large volumes of polyethylene glycol electrolyte solution (PEG-ES) in combination with a clear-liquid diet (CLD). Liberalization of the diet might enhance the tolerance to PEG-ES without compromising the quality of the preparation. The primary aims of this study were to evaluate the efficacy and tolerability of PEG-ES given with a CLD compared with a fiber-free diet (FFD) for colonoscopy preparation. The incidence of adverse events among patients in the two diet groups was also assessed as a secondary outcome. METHODS: This was a single-center randomized, prospective, single-blind study. A total of 200 patients undergoing colonoscopy were randomized to either CLD or FFD in addition to PEG-ES. RESULTS: Patients in the FFD group were able to drink more PEG-ES (mean +/- SD, 3.9 +/- 0.3 L) compared with those in the CLD group (3.3 +/- 0.7 L) ( P < 0.01). The quality of the preparation was significantly better in the FFD group, with more patients having satisfactory preparations than those in the CLD group (81.4 % vs. 52.0 %; P < 0.001). Tolerance to the preparation was higher in the FFD group compared with the CLD group, with significantly more patients adhering to the FFD regimen ( P < 0.001). There were more adverse events experienced in the CLD group, with odds ratios of 1.9 for nausea (95 % confidence interval [CI] 1.0 - 3.6), 3.8 for vomiting (95 % CI 1.3 - 11.3), and 3.0 for headache (95 % CI 1.5 - 5.9). CONCLUSION: FFD given with PEG-ES on the day before colonoscopy is a more effective regimen than the standard CLD regimen, and is better tolerated by patients.

Clinical trial: a randomized controlled cross-over study of flupenthixol + melitracen in functional dyspepsia.

BACKGROUND: Functional dyspepsia is a prevalent condition associated with diminished quality of life (QoL) and high economic burden. AIM: To study the efficacy of a combination of flupenthixol and melitracen (F + M) with anxiolytic and antidepressant properties in functional dyspepsia using a randomized controlled cross-over design. METHODS: Patients met the Rome III criteria for functional dyspepsia and a validated questionnaire was used to exclude those with anxiety or depression. Moreover, patients had to have failed a trial of acid-suppressive therapy and Helicobacter pylori eradication when positive. End points included subjective global symptom relief and QoL assessed by the Nepean Dyspepsia Index (NDI). RESULTS: Twenty-five patients (14 females, 11 males; mean age = 34.3 +/- 9.9 years) were enrolled and 24 completed the 8-week study. There was a significant improvement in subjective global symptom relief with F + M vs. placebo (ITT: 73.9% vs. 26.1%, P = 0.001) and a significant drop in the NDI score vs. placebo (ITT: -9.0 +/- 11.9 vs. -2.4 +/- 8.9, P = 0.03). No difference was noted whether the initial treatment was F + M or placebo. No significant side effects were noted. CONCLUSIONS: A combination of F and M is safe and effective in the short-term treatment of functional dyspepsia. F + M is associated with significant improvement in QoL independent of the presence of anxiety or depression.

Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease.

Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C virus (HCV)-infected patients and it increased with increasing severity of the liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was 16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone positive patients compared to only 7.1% in healthy controls who were also anti-HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with increasing severity of the liver disease, but this increase was only marginally significant and, perhaps, could have been significant if more patients were involved in the study. Although Lebanon is an area of low endemicity for both HBV and HCV, occult HBV infection is common in HCV-infected patients. The presence of HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV detection methods are not used.

Genotypes of hepatitis C virus (HCV) among positive Lebanese patients: comparison of data with that from other Middle Eastern countries.

Recently we identified hepatitis C virus (HCV) genotype 4 as the principle genotype among Lebanese thalassaemics. In an attempt to confirm the predominance of genotype 4 in Lebanon and perhaps in the Middle East, genotyping was attempted on 142 HCV-infected Lebanese patients from five different hospitals in the country. These included 38 HCV-positive patients with symptomatic liver disease who were referred to gastroenterologists and 104 HCV-positive patients with no symptoms of liver disease: 27 patients with thalassaemia, 30 patients on haemodialysis, 32 multi-transfused and 15 intravenous drug users. HCV genotyping was performed on PCR HCV RNA-positive samples using a commercial line probe assay (LiPA; Innogenetics, Ghent, Belgium). HCV genotype 4 is found to be the predominant genotype among HCV-infected Lebanese patients (ranging from 34.2% to 53.3%) followed by 1a (ranging from 12.5% to 43.3%) and 1b (ranging from 8.0% to 34.4%). In patients with symptomatic liver disease, however, genotype 4 (34.2%) was preceded by genotype 1a (39.5%). The predominance of HCV genotype 4 in our population (45.7%) confirms the predominance of HCV genotype 4 in Lebanon and most of the Arab countries in the Middle East but contrasts with data reported from non-Arab Middle Eastern Countries as can be seen from the literature review. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.

Current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in Lebanon.

Recently the prevalence of hepatitis B virus (HBV) genotypes and the association between these genotypes and the clinical status of HBV-infected patients were recently investigated in the Lebanese population. The aim of the additional study reported here was to determine the current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in this Lebanese population. Two hundred and fifty-eight HBsAg-positive patients (107 asymptomatic blood donors, 92 with chronic hepatitis, 24 with cirrhosis, 15 with hepatocellular carcinoma, 20 patients on haemodialysis) from ten medical centers in Lebanon were tested for antibody to hepatitis D virus (anti-HDV). Those testing positive were analysed further for HDV-RNA and for genotyping by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Three samples (1.2%) were anti-HDV positive and out of these, only one was HDV-RNA positive (0.6%) and was analysed as HDV genotype I. Our results point to a low endemicity of HDV in the Lebanese population which is in sharp contrast to data reported from Lebanon 20 years ago and to the situation in neighbouring Arab and non-Arab countries in the Mediterranean region. HDV genotype I seems to be the predominant genotype in Lebanon and the Middle East.

Association of gastroduodenal disease phenotype with ABO blood group and Helicobacter pylori virulence-specific serotypes.

AIMS: To investigate the prevalence of Helicobacter pylori infection in Lebanon and the association between virulence factors (cytotoxin-associated gene A and vacuolating cytotoxin gene A), ABO blood groups, and disease phenotype. METHODS: One hundred and thirty symptomatic patients with H. pylori-associated endoscopic findings and 104 healthy male donors (age range 18-55) were evaluated. Both, patients and donors underwent ABO blood typing and Western blot for cytotoxin-associated gene A and vacuolating cytotoxin gene A. RESULTS: The prevalence of H. pylori infection in healthy donors is 68.3%. Type I (cytotoxin-associated gene A- and vacuolating cytotoxin gene A-positive) was the predominant phenotype in all groups, though significantly less common in the asymptomatic population (46.5%) than in patients with benign disease (71.4%, p<0.01) or malignancy (71.6%, p<0.05). Type II (cytotoxin-associated gene A- and vacuolating cytotoxin gene A-negative) and vacuolating cytotoxin gene A-only strains were more common in the asymptomatic cohort. Overall, 35.2% of asymptomatic individuals and 10.8% of patients with benign disease were cytotoxin-associated gene A-negative (p<0.01). There was no significant association between immunoserotypes, ABO groups or benign gastroduodenal disease. All gastric malignancies (lymphoma and adenocarcinoma) were cytotoxin-associated gene A-positive but this was not significantly different from patients with benign disease. We found a higher prevalence of blood group A in patients with gastric malignancy than in the general population [47.6% versus 25%, p=0.037; RR=2.73 (1.04-7.16; 95% CI)]. CONCLUSIONS: The seroprevalence of H. pylori is moderately high in Lebanon. Phenotypic classification identifies a higher prevalence of Type I in symptomatic patients. A significant relationship between infection with a cytotoxin-associated gene A-positive strain in blood type A patients and the risk of gastric malignancy was noted.

Recurrent massive haemorrhage from an endoscopically inevident isolated rectal varix.

Anorectal varices are identified endoscopically in up to 40% of patients with liver cirrhosis [Misra SP, Dwivedi M, Misra V. Prevalence and factors influencing haemorrhoids, anorectal varices, and colopathy in patients with portal hypertension. Endoscopy 1996;28:340-5] but are an infrequent cause of bleeding and their management remains controversial. We present a patient with chronic hepatitis C virus infection who developed recurrent haemorrhage from an isolated, endoscopically inevident rectal varix in the absence of clinical or endoscopic evidence of portal hypertension. The difficulties in diagnosis and management of anorectal varices are highlighted.

Five-year trial of deferiprone chelation therapy in thalassaemia major patients.

Twelve thalassaemia major patients have been given deferiprone 75 mg/kg body weight daily as iron chelation therapy for 5 years. Their ages ranged from 18 to 34 years (mean 24.2) at the end of the study. Two patients were hepatitis C virus (HCV) mRNA positive and a further 5 were positive for HCV antibody. The mean serum ferritin level fell significantly from 4,302 +/- 2,245 microg/l SD at baseline to 3,032 +/- 1,155 microg/l at 2 years (p = 0.037) and 2,229 +/- 1,070 microg/l (p = 0.007) at 5 years. At the end of the study, liver iron ranged from 3.59 to 23.7 mg/g dry weight (mean 11.9 +/- 5.4), 3 patients having levels >15 mg/g. There was no significant change in serum AST levels, but ALT levels fell significantly at 2 years (p = 0.019) and 5 years (p = 0.001). Liver biopsy at the end of the study showed no evidence of hepatic fibrosis caused by deferiprone. Cardiac studies showed no overall change in left ventricular ejection fraction but a significant improvement in isovolumic relaxation time (p = 0.045). We conclude that in this albeit small group of thalassaemia major patients, deferiprone was a safe long-term method of iron chelation. In a minority, higher doses of deferiprone or a combination with desferrioxamine would be needed to lower liver iron below 15 mg/g.

Cytomegalovirus appendicitis following acute Epstein-Barr virus infection in an immunocompetent patient.

Acute appendicitis due to cytomegalovirus is exceedingly rare. It occurs mostly in individuals with the acquired immunodeficiency syndrome and has been reported once in an immunocompetent patient. This report describes a man who developed acute appendicitis following acute Epstein-Barr virus infection, and in whom cytomegalovirus was incriminated based on pathological examination.

Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study.

BACKGROUND: The measurement of the hepatic venous pressure gradient may identify a suboptimal response to beta-blockers in patients with varices at risk for bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide primary prophylaxis has not been examined. METHODS: We used decision analysis to evaluate two hepatic venous pressure gradient measurement strategies relative to standard beta-blocker therapy in a hypothetical cohort of patients with high-risk varices: (i) hepatic venous pressure gradient measurement 4 weeks after the initiation of beta-blocker therapy; and (ii) hepatic venous pressure gradient measurement prior to and 4 weeks after the initiation of beta-blocker therapy. The total expected costs, variceal bleeding episodes and deaths were calculated over a 1-year time horizon. RESULTS: Beta-blocker therapy was associated with total costs of $1464, seven variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. One hepatic venous pressure gradient measurement was associated with total costs of $5015, four variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. Two hepatic venous pressure gradient measurements were associated with total costs of $8657, four episodes of variceal bleeding, one variceal bleeding episode-related death and 15 deaths. Compared with beta-blocker therapy alone, the incremental costs per variceal bleeding episode prevented and death averted were, respectively, $108 185 and $355 100 (one hepatic venous pressure gradient measurement) and $202 796 and $719 300 (two hepatic venous pressure gradient measurements). The results were sensitive to the time horizon of the analysis, the probability of bleeding whilst on beta-blockers and the cost of hepatic venous pressure gradient measurement. CONCLUSION: Hepatic venous pressure gradient measurement to guide primary prophylaxis is an expensive strategy for reducing variceal bleeding or death, especially in patients with limited life expectancy, such as those with advanced, decompensated cirrhosis.

Effect of aggressive therapy on laryngeal symptoms and voice characteristics in patients with gastroesophageal reflux.

Gastroesophageal reflux (GER) is associated with a variety of laryngopharyngeal signs and symptoms. Injury of the laryngopharynx as a result of GER can be refractory to conventional antireflux therapy. This prospective study was undertaken to evaluate the prevalence of laryngopharyngeal signs and symptoms in patients with documented GER and to assess the response to a high-dose combination antireflux therapy consisting of cisapride and pantoprazole. Twenty-two patients with symptoms of GER were enrolled. After baseline evaluation using a history questionnaire for symptoms, laryngeal endoscopy and vocal acoustic analysis, patients were started on treatment consisting of pantoprazole 40 mg b.d. and cisapride 20 mg twice daily. Repeat history and otolaryngologic evaluation was performed at 4 weeks. Laryngopharyngeal symptoms were frequent in most patients, with throat clearing and globus being the most prevalent symptoms followed by vocal fatigue and excess mucus production. Almost 90% of the patients had abnormal endoscopic laryngeal findings but the acoustic parameters did not show any abnormal results except for mild elevation in the shimmer. After treatment, all symptoms and endoscopic abnormalities improved significantly except for intermittent dysphonia and laryngeal mucosal redness. Acoustic abnormalities did not change significantly following therapy. Laryngeal symptoms and voice abnormalities are highly prevalent in patients with GER. Combination antireflux therapy with a proton pump inhibitor and a prokinetic agent results in rapid symptomatic and endoscopic response in the majority of patients.