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 In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature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.

Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-alpha in vivo.

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) gamma and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-alpha serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-alpha caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-alpha also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-alpha therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-alpha treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-alpha-treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-alpha-enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-alpha treatment of cells in vitro or administration of IFN-alpha to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-alpha in hepatitis C infection.

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.

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.

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.

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.

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.

Hepatitis C in pregnancy.

OBJECTIVE: To review the epidemiology and clinical course of hepatitis C virus (HCV) infection, to examine current data on the vertical transmission of HCV to neonates, and to develop recommendations for intrapartum and postpartum follow-up of neonates born to HCV-infected mothers. DATA SOURCES: The English-language medical literature from 1988 to 1996 was reviewed through MEDLINE. METHODS OF STUDY SELECTION: Case series evaluating vertical transmission of HCV infection in neonates, determined by HCV RNA testing, after delivery and breast-feeding were reviewed and summarized. TABULATION, INTEGRATION, AND RESULTS: Vertical transmission of HCV infection was examined with respect to maternal human immunodeficiency virus (HIV) status (as heterosexual transmission of HCV is enhanced in HIV-positive patients) and chronicity of HCV infection. Vertical transmission of HCV from HIV-negative mothers with chronic hepatitis C ranged from 0 to 18%. The risk of HCV vertical transmission from HIV-negative mothers with acute hepatitis C may be higher than that from mothers with chronic HCV infection. Vertical transmission of HCV was proportional to maternal HCV RNA levels; no transmission was noted in women without HCV RNA, whereas the greatest transmission was noted in women with HCV RNA greater than 1 million copies/mL. Vertical transmission of HCV from HIV-positive mothers with chronic hepatitis C ranged from 6 to 36%. In colostrum, HCV RNA was found to be present in low titers. No studies have documented transmission of HCV infection to infants via breast-feeding. CONCLUSION: Vertical transmission of HCV complicates up to 18% of pregnancies in HCV-positive, HIV-negative women and 6-36% in HCV-positive, HIV-positive women. The highest rates of vertical transmission of HCV were noted in women with high HCV RNA or concurrent HIV infection. Breast-feeding has not been associated with vertical transmission of HCV infection.

Acute granulomatous schistosomal cholecystitis.

Schistosomal cholecystitis is a rare entity with less than 10 cases described in the medical literature [1-3]. It is unclear whether schistosomal eggs deposited in the wall of the gallbladder trigger a clinically manifest acute cholecystitis, since most of the cases described were also found to have concomitant gallstones. Herein, we report a patient who developed acute schistosomal granulomatous acalculous cholecystitis. The clinical presentation, chronology of events and pathological findings strongly support the association between cholecystitis and schistosomal infection.

Ultrashort regimen of lansoprazole-amoxicillin-azithromycin for eradicating Helicobacter pylori.

The efficacy and safety of two ultrashort azithromycin-containing regimens for Helicobacter pylori infection were studied. Patients positive for H. pylori infection were assigned to receive either a three-day drug regimen (group A) or a five-day regimen (group B). In both groups, patients received lansoprazole 30 mg p.o. twice daily on day 1 and, on days 2 and 3, lansoprazole 30 mg p.o. twice daily, amoxicillin 1 g (of anhydrous amoxicillin) p.o. twice daily, and azithromycin 500 mg (of anhydrous azithromycin) p.o. twice daily. Group B patients received lansoprazole 30 mg p.o. twice daily and amoxicillin 1 g p.o. twice daily for two additional days. Gastric biopsy specimens were subjected to culture and susceptibility testing. A minimum of four weeks after the completion of therapy, the patients underwent a 14C-urea breath test to determine whether H. pylori had been eradicated. A total of 28 patients were enrolled (15 in group A and 13 in group B). Treatment was well tolerated. H. pylori was eradicated in 4 (36%) of 11 patients in group A and 2 (22%) of 9 group B patients (26.6% and 15.4%, respectively, in intention-to-treat analysis). None of the isolates of H. pylori showed resistance to amoxicillin or clarithromycin. Regimens consisting of lansoprazole plus two or four days of azithromycin and amoxicillin therapy eradicated H. pylori in 36% and 22% of patients, respectively.

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.

Diagnosis and management of chronic hepatitis C.

Chronic HCV infection is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. The disease is indolent or subclinical in the majority of patients but alcohol consumption and older age at infection may be associated with an accelerated course. Current diagnostic modalities are highly sensitive and specific in confirming the diagnosis and may help predict response to therapy. Treatment with interferon is effective in clearing the virus in a small number of patients but the addition of ribavirin results in an enhanced overall chance of viral eradication. The development of an effective vaccine to HCV is presently encumbered by the presence of multiple viral genomic subtypes and the high rate of spontaneous viral mutation leading to limited efficacy of neutralizing antibodies.