Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Audit of state-funded antiviral treatment for chronic hepatitis C in Qatar.

Hepatitis C virus (HCV) infection is a major public health problem in the Middle East. A database of 400 patients with chronic HCV in Qatar was retrospectively analysed: 242 patients underwent antiviral treatment, of whom 212 (87.6%) were naïve to treatment. The response to treatment and the predictors of response were studied. The largest group of patients were of Egyptian origin. The rate of sustained virological response (SVR) varied significantly between patients with HCV genotypes 2 or 3 (79.6%) and genotype 1 (45.6%) and 4 (the predominant genotype) (51.0%). Multivariate analysis showed that the independent predictors of SVR were age < 45 years, infection with genotypes 2 or 3, low fibrosis score on liver biopsy and naïve treatment status.

Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatment.

Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively).In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X(2) = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X(2) = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X(2) = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X(2) = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment.

Viral kinetic of HCV genotype-4 during pegylated interferon alpha 2a: ribavirin therapy.

Kinetics of hepatitis C virus (HCV) during pegylated interferon (PEG-IFN) and early monitoring of viral decline were recently described to predict treatment outcomes and in turn reduce the course of treatment, adverse effects and cost. However, there is limited (if any) information on the viral dynamics of HCV-4. Our aim is to follow the HCV-RNA kinetics during PEG-IFN alpha 2a and ribavirin therapy and the best time for predicting sustained viral response (SVR) in genotype-4 patients. Serum HCV-RNA levels before initial dosing (baseline level) and at 24 h, week 1, week 4, week 12, week 24, week 48 and week 72 were assessed in 84 HCV genotype-4 patients treated weekly by PEG-IFN alpha 2a and daily ribavirin. At the end of treatment, out of the 84 treated patients, 19 (22.6%) were non-responders while 65 (77%) showed end-of-treatment response (ETR). However, 8 patients relapsed (9.5%), thus the SVR was observed in 57 patients (67.9%). Younger patients were more likely to attain SVR, where the odds of SVR increased by a factor of 0.94 for each year increase in age (95% CI: 0.90-0.99, P = 0.019). Although a significant negative correlation between stage of fibrosis and rate of viral decline at weeks 1 and 4 (P < 0.005 and 0.001, respectively) was seen, neither fibrosis stage (χ(2) = 3.4882, P > 0.1) nor grade of inflammation (χ(2) = 0.0057, P > 0.1) significantly predicted response to treatment. Non-responders had no or only a limited decline at week 1 and week 4, whereas sustained virological responders had a significant decline at both week 1 and week 4. Area under the (receiver operating characteristic) curve (AUC) revealed that week 12 is better than any other time point in predicting the SVR (AUC = 0.97; 95% CI: 0.94-1.01), (sensitivity 98.3%; 95% CI: 90.7-99.9), (specificity 88.5%; 95% CI: 71.0-96.0), positive predictive value of 94.9% and negative predictive value of 95.8%. A drop of more than 1.17 log viral load at week 1 and viral clearance or decline >3 log were considered as the earliest predictors of SVR. In genotype-4 patients, while failure to achieve an EVR at week 12 predicts non-response, an RVR at week 1 and week 4 98% guaranteed SVR. These findings further re-enforce the value of week 12 in the course of IFN treatment. Genotype-4 patients who show significant viral clearance (>1.17 log viral load) by the first week of treatment and viral clearance >3 log by week 4 are expected to show SVR and should therefore be assigned to a shorter drug regimen lasting for 24 weeks. Those unfortunate cases who do not achieve viral clearance by week 1 or week 4 should not be deprived from the treatment but rather given more time till week 12 before being classified as non-responders.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: impact of bilharziasis and fibrosis stage.

AIM: To evaluate pegylated interferon alpha2a (PegIFN-alpha2a) in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS: A total of 73 naive patients (61 with history of bilharziasis) with compensated chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients) received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS: Significant improvement in both end of treatment response (ETR) (P < 0.002) and sustained response (SR) (P < 0.05) was noted with pegylated interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B could retain negative viraemia by the end of follow up period. Sustained virological response (SVR) showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR (P < 0.001), but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis (grade 3 and 4) with PegIFN-alpha2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect; both drugs were comparable. CONCLUSION: PegIFN-alpha2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.

Frequency of peptic ulcer disease during and after Ramadan in a United Arab Emirates hospital.

We aimed to study the effect of Ramadan fasting on the occurrence of peptic ulcer disease and its complications in patients presenting to the Accident and Emergency Department at Al-Ain hospital, United Arab Emirates (UAE). We retrospectively reviewed patient records over the 10-year period, 1992 to 2002. Of 470 patients treated for peptic ulcer disease, 215 were seen during Ramadan and 255 in the month after Ramadan. The frequency of peptic ulcer disease was higher after Ramadan than during Ramadan but this was not statistically significant. Peptic ulcer disease occurred more frequently in the age group 30-49 years. Peptic ulcer perforation occurred more frequently after Ramadan but the difference was not significant. Regression analysis identified the following variables as predictors of peptic ulcer disease: anorexia, pain, hypertension, smoking, epigastric pain, diabetes and family history.

A comparative ultrastructural study of the Helicobacter pylori in duodenal ulcer patients before and after treatment.

Full text is available as a scanned copy of the original print version.

Hepatitis C virus infection in hemodialysis patients in qatar.

To evaluate the prevalence of hepatitis C virus (HCV) infection and the histopathological aspects of this infection among regular hemodialysis patients, we followed 130 patients on regular dialysis screened for HCV antibodies by enzyme-linked immunosorbent assay (ELISA). Confirmatory testing was done using a second generation recombinant immunosorbant assay (RIBA). Fifty eight patients (44.6%) were antibody positive at the start of the study. There was a significant relationship between the presence of anti-HCV antibody and the increased period on dialysis (54.3 months in the sero-positive group, compared to 22.2 months in the sero-negative group, (P < 0.001). There was no statistical correlation with the history of blood transfusion or the serum iron level. Liver biopsies in eight sero-positive patients with abnormal liver enzymes showed chronic active hepatitis in six and chronic persistent hepatitis in two cases. Such findings of gross hepatic involvement in anti-HCV positive hemodialysis patients strongly support the arguments for antiviral therapy with Interferon in these patients, in the attempt to prevent further hepatic damage, before they receive renal allografts.

The Impact of Hepatitis C Infection and Antiviral Therapy on clinical Outcome in Renal Transplantation Recipients.

Hepatitis C viral infection (HCV) is presently a major problem in renal transplant recipients (RTR) with a high risk of chronicity resulting in liver cirrhosis. We screened 120 RTR (50 live related, 53 live unrelated, and 17 cadaveric); mean age of 45.2 years and mean post-transplant period of 6.8 years. Positive HCV antibodies using RIBA-2 test were detected in 43 patients (35.8%). Polymerase chain reaction was performed on 37 seropositive patients and confirmed viremia in 100% of hem. Forty-one seropositive patients (95.3%) had previous dialysis prior to transplantation; a mean of 4.5 years. Liver disease manifested in only five (11.6%) of the seropositive patients and hypertransaminasemia was detected in 14 (32.6%). Twelve seropositive patients with elevated transaminase levels and/or clinical evidence of liver disease, who all had positive PCR, underwent liver biopsy. Inflammation restricted to portal area was noticed in two, persistent hepatitis in three, chronic active hepatitis in four and cirrhosis in three. There was significantly higher incidence (P< 0.03) of acute graft rejection in the seropositive (23.3%) compared to the seronegative patients (9.1% ). While the difference did not amount to statistical significance for chronic rejection (9.3% and 6.5% respectively). Two patients had acute cellular rejection related to interferon therapy. The leading cause of death was related to liver failure in the seropositive patients and coronary artery disease in he seronegative RTR. In conclusion, there is high incidence of HCV in or renal transplant recipients associated with relatively high morbidity and mortality. At present we are lacking an efficient and well-tolerated antiviral drug.

Should doctors inform terminally ill patients? The opinions of nationals and doctors in the United Arab Emirates.

OBJECTIVES: To study the opinions of nationals (Emiratis) and doctors practising in the United Arab Emirates (UAE) with regard to informing terminally ill patients. DESIGN: Structured questionnaires administered during January 1995. SETTING: The UAE, a federation of small, rich, developing Arabian Gulf states. PARTICIPANTS: Convenience samples of 100 Emiratis (minimum age 15 years) and of 50 doctors practising in government hospitals and clinics. RESULTS: Doctors emerged as consistently less in favour of informing than the Emiratis were, whether the patient was described as almost certain to die during the next six months or as having a 50% chance of surviving, and even when it was specified that the patient was requesting information. In the latter situation, a third of doctors maintained that the patient should not be told. Increasing survival odds reduced the number of doctors selecting to inform; but it had no significant impact on Emiratis' choices. When Emiratis were asked whether they would personally want to be informed if they had only a short time to live, less than half responded in the way they had done to the in principle question. CONCLUSIONS: The doctors' responses are of concern because of the lack of reference to ethical principles or dilemmas, the disregard of patients' wishes and dependency on survival odds. The heterogeneity of Emiratis' responses calls into question the usefulness of invoking norms to explain inter-society differences. In the current study, people's in principle choices did not provide a useful guide to how they said they would personally wish to be treated.

Audit of state-funded antiviral treatment for chronic hepatitis C in Qatar

Hepatitis C virus [HCV] infection is a major public health problem in the Middle East. A database of 400 patients with chronic HCV in Qatar was retrospectively analysed: 242 patients underwent antiviral treatment, of whom 212 [87.6%] were naive to treatment. The response to treatment and the predictors of response were studied. The largest group of patients were of Egyptian origin. The rate of sustained virological response [SVR] varied significantly between patients with HCV genotypes 2 or 3 [79.6%] and genotype 1 [45.6%] and 4 [the predominant genotype] [51.0%]. Multivariate analysis showed that the independent predictors of SVR were age < 45 years, infection with genotypes 2 or 3, low fibrosis score on liver biopsy and naive treatment status

Frequency of peptic ulcer disease during and after Ramadan in a United Arab Emirates hospital

We aimed to study the effect of Ramadan fasting on the occurrence of peptic ulcer disease and its complications in patients presenting to the Accident and Emergency Department at Al-Ain hospital, United Arab Emirates [UAE]. We retrospectively reviewed patient records over the 10-year period, 1992 to 2002. Of 470 patients treated for peptic ulcer disease, 215 were seen during Ramadan and 255 in the month after Ramadan. The frequency of peptic ulcer disease was higher after Ramadan than during Ramadan but this was not statistically significant. Peptic ulcer disease occurred more frequently in the age group 30-49 years. Peptic ulcer perforation occurred more frequently after Ramadan but the difference was not significant. Regression analysis identified the following variables as predictors of peptic ulcer disease: anorexia, pain, hypertension, smoking, epigastric pain, diabetes and family history