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 In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were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.

Emerging role for colorectal cancer screening in Asian countries.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading causes of cancer related mortality globally. Though Asia has traditionally been considered a relatively low incidence area for colorectal cancer, the incidence is reportedly increasing. The Asia Pacific Working Group for Colorectal Cancer has recommended screening of individuals at average risk starting from 50 years of age. Based on these recommendations we conducted a pilot study to assess the need and feasibility of a colorectal cancer screening program in the state of Qatar. METHODS AND RESULTS: We screened 1385 individuals by fecal immunochemical testing for occult blood, at the primary health center level and positive cases were referred for colonoscopy. Among those who tested positive for fecal occult blood, we picked up five patients with cancers and seven with neoplastic polyps. CONCLUSION: Our results compare with the yield of screening programs in western countries thus suggesting an emerging role for colorectal cancer screening in Asian countries.

Embryo transfer into anestrous recipient mares prepared using clomiphene citrate and short-acting progesterone.

Embryo transfer (ET) is an important technology for genetic improvement programs in the equine industry. Many protocols have been used for preparation of recipients. This study evaluates a new protocol for preparation of acyclic embryo recipient mares using clomiphene citrate (CC) and short-acting oral progesterone (Altrenogest). Seventy-two native breed recipient mares were divided into 2 groups. Group 1(G1) included 60 non-cyclic mares with follicular structures ≤ 15 mm in diameter that received CC and Altrenogest. Group 2 (G2) included 12 cyclic recipient mares that served as a control group. G1 mares were treated with oral CC at a dose of 250 mg for 4 days followed by oral administration of Altrenogest for 6 days. Ultrasonography was carried out for evaluation of uterine echotexture response to hormonal treatment, and pregnancy diagnosis post ET. Serum estradiol and progesterone concentrations were also assessed. All data were statistically analyzed. The results revealed that the serum progesterone concentrations in G1 were higher than G2 (P < 0.001). There was no difference in the estradiol concentrations between both groups during diestrus phase (P > 0.05). The pregnancy rate was higher in G1 (83.3 %) than G 2 (66.6 %). In conclusion, using oral CC and Altrenogest, as a new protocol, was effective for preparation of acyclic recipient mares in this study.

A novel method for equine embryo transfer from contaminated recipient mares into second healthy recipients for surviving embryos.

Embryo transfer (ET) is regarded as one of the reproductive methods for genetic improvement initiatives in the horse business. The current study aimed to increase the success rate of ET by re-flushing and re-transferring of embryos from contaminated recipient mares into second healthy recipients. The study involved 25 recipient mares that demonstrated embryonic vesicles inside intraluminal fluid (ILF) on ultrasound scanning 2 ± 0.5 days after ET. Seven recipient mares were left without re-flushing and re-transferring of embryos (control group) and 18 recipient mares (treated group) were subjected to re-flushing and re-transferring of the embryos to second healthy and prepared recipients. The retrieved fluid from treated mares was subjected to microbiological and cytological examinations. The results revealed mixed and single infections, as well as polymorphonuclear neutrophils (PMNs). The total bacterial count and cytology findings revealed that all first recipient mares had endometritis. All control mares showed embryonic death at 14 ± 1.1 days (13-15 days) of embryonic age. In treated group, microscopic evaluation of retrieved embryos revealed a well-developed thick capsule in 12/18 (66.7 %) of them and a normal capsule in 6/18 (33.3 %). The pregnancy rate in well-developed capsule embryos was greater (66.7 %) than in typical capsule embryos (33.3 %). This study illustrates the value of swabbing the uterus of the recipient mares during estrus prior to ET and their checking at 2 days after ET. In addition to boosting pregnancy rates in ET commercial programs, our novel method can protect the embryos from the harmful effects of the inflammatory process and help them survive.

A case of a twin surviving to term following the abortion of its co-twin at 9 months in an Arabian mare.

Twin pregnancy in mares is one of the leading causes of abortions. Abortion invariably impacts both fetuses. This report describes an unusual case of a twin surviving to term following the abortion of its co-twin at 9 months in a 7-year-old Egyptian Arabian mare. At the time of abortion at 9 months of gestation, the size of the aborted fetus was equivalent to one of approximately 5 months of age while the age of the live co-twin was 9 months. Both fetuses were males. A skin sample was collected from the aborted fetus and hair samples were collected from the dam, sire and live foal for parentage analysis. The parentage analysis confirmed that both fetuses were by the same dam and sire stallion. The authors suggest several scenarios to explain this condition. This report describes a unique case of a twin surviving to term following the abortion of its co-twin at 9 months in a mare.

Hepatitis C virus genotype 4 with normal transaminases: histological changes, schistosomiasis and response to treatment.

Among individuals with chronic hepatitis C virus (HCV) infection, approximately 30% of patients show persistently normal alanine aminotransferase (PNALT). Individuals with PNALT have been historically excluded from antiviral treatment. However, some studies have reported sudden worsening of disease in patients with PNALT, suggesting the need to treat such individuals. To evaluate this further, we compared fibrosis severity and response to treatment in patients with PNALT to patients with abnormal ALT. In addition, we investigated whether liver histology and schistosomiasis affect response to treatment differently in those with PNALT and abnormal ALT. A retrospective cohort study of 176 HCV-Genotype 4 (HCV-G4) patients treated with pegylated interferon (PEG-IFN) and ribavirin. Of 176 cases studied, 53 (30.1%) had normal ALT. Prevalence of pretreatment severe fibrosis, sustained virological response (SVR) and relapse were not significantly different in patients with PNALT (26%, 66% and 5.7% respectively) compared to those with abnormal ALT (32.5%, 60.7%, and 6.6% respectively). Multivariable logistic regression revealed that pretreatment ALT, pretreatment viral load, inflammation and schistosomiasis were not significantly associated with SVR [OR (95% CI), 0.75 (0.34-1.65); 0.92 (0.61-1.37); 1.64 (0.64-4.18); 0.90 (0.44-1.84) respectively]. Severe fibrosis was the only significant predictor of SVR [OR (95% CI), 0.38 (0.14-0.99)]. PNALT does not reflect the degree of fibrotic changes or predict SVR. Furthermore, schistosomiasis is a predictor of neither fibrosis nor poor response in patients with PNALT. Severe fibrosis is a strong and independent predictor of response to treatment. Therefore, it is important to treat individuals with PNALT levels regardless of schistosomiasis.

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.

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis jiroveci infection in orthotopic liver transplantation.

We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans organizing pneumonia (BOOP). We present this second case of BOOP associated with P. carinii pneumonia after OLT to highlight the risk of such disease combination in all transplant patients as well as discuss the protective effect of post-transplant prednisolone with trimethoprim-sulfamethoxazole prophylaxis and the possible duration of prophylaxis.

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.

Pegylated interferon-alpha 2b-ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis.

Egypt has a high prevalence rate of hepatitis C (HCV) infection and as much as 90% is genotype 4. Response to interferon (IFN) varies with viral genotype and degree of fibrosis. Genotype 4 is poorly sensitive to standard IFN and IFN-ribavirin combination. We evaluated pegylated interferon (PEG-IFN)-alpha2b in our patients. Sixty-one patients with compensated chronic HCV genotype 4 were enrolled in two groups: group A (31 patients) received IFN-alpha2b 3 MU three times per week and group B (30 patients) received 1.5 mug/kg PEG-IFN-alpha2b once weekly. Ribavirin was added to each regimen in a dose of 800-1200 mg based on body weight. Patients were followed up for 24 weeks to assess the sustained response (SR). End-of-treatment response (ETR) was achieved in 11 of 31 patients (35.48%) in group A, and 13 of 30 patients (43.33%) in group B (P < 0.05). Only eight patients in group A and 10 in group (B) achieved a sustained virological response (25.8 and 33.3%, respectively) (P < 0.05). By computing ETR, SR or relapse and pretreatment baseline data (pretreatment, viral load, alanine transaminases, necroinflammatory and hepatic fibrosis), both inter- and intragroup, no significant correlations could be detected. In terms of safety and tolerability, PEG-IFN-alpha2b and IFN-alpha2b were comparable. In spite of mild insignificant increase in ETR and SR with the pegylated form, the poor response of genotype 4 in Egypt (genotype 4a) to different forms of IFNs may be related to an intrinsic resistance to the direct antiviral effect of IFN.

A monoclonal antibody diagnoses active Fasciola infection in humans.

Monoclonal antibodies (MABs) were produced after fusion of spleen cells of Fasciola antigen immunized BALB/c mice and non secreting murine myloma cells (P3x63 Ag8). Six MAbs, showing the highest reactivity with purified Fasciola antigen, were prepared. All 6 MABs were IgG2 with Kappa light chain. Reactive epitopes recognized by the six MAbs were glycoprotein in nature, and each MAb recognized a single epitope of Fasciola antigen. No cros reactions were observed with Schistosomal AWSA, hydatid Ag and Entamoeba Ag. EITB technique showed a specific diagnostic band at 17.5 kDa for each of the six MAbs. Anti-Fasciola MAb (AD2) was conjugated with peroxidase and was used with anti-rabbit anti-Fasciola polyclonal antibody in sandwich-ELISA to detect circulating Fasciola antigen in serum and urine samples of 57 fascioliasis patients, 51 schistosomiasis patients, 45 patients infected with other parasites and 47 healthy controls. Sensitivity of the assay in detection of circulating Fasciola antigen in sera and urines of Fasciola infected patients was 100%. The specificity of the assay was calculated among patients infected with schistosomiasis and other parasites and was 98% in serum and 97% in urine. A positive correlation was found between levels of circulating Fasciola antigen in serum and urine samples of fascioliasis patients (r = 0.825, p < 0.05).

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