The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Serum antibodies to enterohepatic Helicobacter spp. in patients with chronic liver diseases and in a population with high prevalence of H. pylori infection.

BACKGROUND: Enteric Helicobacter species might be a risk factor for chronic liver and biliary tract diseases. AIMS: To analyse serum antibody levels to three enteric Helicobacter species in patients with various biliary tract and chronic liver diseases and compare results with corresponding parameters for an adult population group, known to have a high prevalence of Helicobacter pylori infection, and with healthy blood donors, to explore a possible association of enteric Helicobacter with chronic liver diseases. SUBJECTS: Sera of 90 patients with various chronic liver diseases, 121 Estonian adult persons and 68 blood donors were analysed. METHODS: Sera, previously tested for H. pylori were analysed for IgG to Helicobacter hepaticus, Helicobacter bilis and Helicobacter pullorum. ELISA was initially used for screening and exclusion of negative cases. Sera with positive ELISA results were further analysed by immunoblot. To remove cross-reactive antibodies between H. pylori and the enteric species, sera were pre-absorbed with lysed H. pylori cells. RESULTS: Liver patients showed a significantly higher seroprevalence to H. hepaticus and H. bilis, compared with the adult population group (p=0.0001 and 0.04, respectively), and to H. hepaticus, compared with blood donors (p=0.01). Patients with autoimmune hepatitis showed no significant antibody reactivity to the enteric Helicobacter spp. in contrast to patients with other chronic liver diseases. CONCLUSION: Patients with chronic liver diseases, except autoimmune hepatitis patients, showed increased antibody levels to H. bilis/H. hepaticus compared with the population and blood donors indicating a possible role of enteric Helicobacter in the natural course of chronic liver diseases. Immunoblot seems to be a promising method for serodiagnosis of infections with these fastidious pathogens.

Hepatitis C virus genotypes in Estonia.

Distribution of hepatitis C virus (HCV) geno(sub)types among 215 Estonian patients hospitalized with acute or chronic hepatitis and with HCV RNA-positive sera was investigated. For genotyping, both multiplex PCR with subtype-specific primers of the core region and RFLP analysis of cDNA of the 5' NCR region were used. These two methods permitted a correct characterization of genotypes, a more truthful characterization of mixed infections, and combined use of single-tube performances. They revealed, respectively, 200 and 202 (93.0% and 93.9%) HCV-positive samples of sera, subtype 1a- 0.9% and 0.9%, 1b- 56.3% and 64.2%, 3a- 13.9% and 22.3%, 2a- 6.5% and 5.6%, type 4 0.5% and 0%, mixed infections- 13.5% and 0%, and unidentified- 1.4% and 0.9%. In the majority of cases (84.7%) both methods gave completely or partially concordant results; in mixed infections, as determined by subtype-specific PCR, only one subtype was revealed by the RFLP method. In the remaining 15.3% of the cases (Ohno- 7.0%, RFLP- 8.3%) only one of the methods was positive. The epidemiological analysis of the dynamics of the subtypes' relative participation may indicate increasing 3a and decreasing 1b subtype infection during recent years.

Polymorphisms in tumour necrosis factor and adhesion molecule genes in patients with inflammatory bowel disease: associations with HLA-DR and -DQ alleles and subclinical markers.

BACKGROUND: When investigating susceptibility to inflammatory bowel disease (IBD), a multifactorial disorder with a genetic predisposition, polymorphisms of molecules with immunoregulatory function are of potential interest. This is the first time that the polymorphisms of HLA-DR and -DQ, tumour necrosis factor (TNF), E-selectin (CD62E), L-selectin (CD62L), and intercellular adhesion molecule 1 (ICAM-1, CD54) were determined in Estonians, a population with a low IBD incidence rate, and their occurrence investigated in subgroups of a total of 53 IBD patients. METHODS: The reverse hybridization principle and sequence specific primers were used for HLA genotyping. To analyse the TNF and adhesion molecule polymorphisms, the polymerase chain reaction with subsequent restriction fragment length polymorphism or single-strand conformation polymorphism method was used. RESULTS: In the subgroup of antineutrophil cytoplasmic antibody (ANCA)-positive ulcerative colitis (UC) patients we found a higher frequency of the TNF2 (20.8% versus 0.0% in ANCA-negative UC patients, P = 0.051) and HLA-DRB1*15 allele (35.4% versus 15.7% in controls; P = 0.004). Of ANCA-positive UC patients 87.5% were carriers of one of these alleles (22.2% among ANCA-negative UC patients (P<0.001, Pc = 0.039) and 51.4% among controls (P = 0.002). Specific typing of HLA-DRB1*15 alleles showed that the HLA-DRB1*1501 allele was responsible for the HLA-DRB1*15 association with ANCA-positive UC. Associations of ICAM-1, E-selectin, or L-selectin polymorphisms with IBD were not found. CONCLUSIONS: TNF2 and HLA-DRB1*15 alleles were associated with ANCA-positive UC in the investigated population. ANCA might be a useful marker, at least in some ethnic groups, for dividing IBD patients into genetically more homogeneous subgroups.

High frequency of antigliadin antibodies and absence of antireticulin and antiendomysium antibodies in patients with ulcerative colitis.

Several authors have described an association between celiac disease (CD) and ulcerative colitis (UC), but this has not yet been established. The aim of our study was to examine the frequency of antigliadin antibodies (AGA), antireticulin antibodies (ARA) and antiendomysium (AEM) antibodies in the sera of patients with UC (n = 50), and to evaluate their correlation with clinical variables. Sixteen patients with irritable bowel syndrome (IBS) and 37 healthy individuals served as controls. An enzyme-linked immunosorbent assay was used for the detection of IgA- and IgG-type AGA. IgG-type ARA were determined by an indirect immunofluorescence assay (IIF) using rat kidney, liver, and stomach as antigen substrates. IgA-type AEM antibodies were measured by IIF, using cryostat sections from human umbilical cord. Seventeen of the 50 patients with UC (34%) were positive for IgA- or/and IgG-type AGA. There was no correlation between the presence of AGA and the duration or extent of the disease, or disease activity. However, 5 patients with both IgA- and IgG-types of AGA had extensive colitis. Only 2 controls (4%) were positive for IgG-AGA. ARA and AEM were not detected in any individuals studied. Since the ARA and AEM test results were negative, we conclude that none of the UC patients in this series had CD.

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role.

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.

[Gastrin cells and the basal level of serum gastrin in patients with insulin-dependent diabetes mellitus]. / Gastrinovye kletki i bazal'nyi uroven' syvorotochnogo gastrina u bol'nykh insulinzavisimym sakahrnym diabetom.

In 40 patients with insulin-dependent diabetes mellitus, the number of gastrin cells in the mucous membrane of the antrum of the stomach was measured by immunohistochemistry according to the method of L. Sternberger. The number of the cells depended on the gravity of antral gastritis, namely their number decreased as the lesion was aggravated. The basal level of serum gastrin was determined by radioimmunoassay in 144 patients with insulin-dependent diabetes mellitus. The high basal level of gastrin was recorded in patients with achlorhydria. However, no correlation was established between the gravity of antral gastritis and the basal level of serum gastrin. If the basal gastrin level is too high, the possibility of asymptomatic paresis of the stomach should be taken into account together with the other factors.