Protocol liver biopsy predicts graft survival after liver transplantation.

BACKGROUND: The use of protocol liver biopsy to monitor liver allograft status remains controversial. There is limited data from modern transplantation populations that includes protocol biopsies to evaluate its value in predicting clinical outcomes. METHODS: All protocol liver biopsies were identified from 875 patients who underwent liver transplantation at Helsinki University Hospital between 2000 and 2019. Each histologic component was analyzed for its ability to predict long-term outcomes, especially graft survival. We determined the frequency of significant biopsy findings based on the Banff working group definition. Liver function tests (LFTs) and clinical markers were evaluated for their ability to predict significant biopsy findings. RESULTS: In total, 867 protocol liver biopsies were analyzed. Significant findings were identified in 20.1% of the biopsies. In the first protocol biopsy, steatohepatitis (hazard ratio [HR] 3.504, p = .03) and moderate or severe congestion (HR 3.338, p = .04) predicted graft loss. The presence of cholangitis (HR 2.563, p = .04), necrosis (HR 7.635, p < .001), mild congestion (HR 4.291, p = .009), and significant biopsy finding (HR 2.540, p = .02) predicted inferior death-censored graft survival. While the degree of elevation of LFTs was positively associated with significant biopsy findings, the discrimination was poor (AUC .572-.622). Combined LFTs and clinical risk factors remained suboptimal for discriminating significant biopsy findings (AUC .696). CONCLUSIONS: Our findings support the use of protocol liver biopsies after liver transplantation since they frequently revealed changes associated with long-term outcomes, even when LFTs were normal.

Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. APPROACH AND RESULTS: Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77-0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow-up (> 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSC ≤ 12 patients, all positive for the biomarkers, included both early-stage and late-stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19-9 levels. CONCLUSIONS: Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 41-50 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P < .001 and HR, 0.90; P = .03, respectively) and malignancy (HR, 0.68; P = .008 and HR, 0.77; P = .004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P < .001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P = .002 and HR, 0.68; P < .001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P < .001 and adjusted HR for women, 0.48; P = .003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P < .001) or no IBD (HR, 1.15; P = .002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.

Value of brush cytology for optimal timing of liver transplantation in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis is associated with a high risk of cholangiocarcinoma. Here, we investigated the value of surveillance for dysplasia using brush cytology, to determine the optimal timing of liver transplantation in primary sclerosing cholangitis. We compared our preoperative findings, with the final explanted liver histopathology. METHODS: 126 consecutive patients were transplanted for primary sclerosing cholangitis from 1984 to 2012. Patients were divided into two groups: symptomatic (n=91), and asymptomatic (n=35). RESULTS: Brush cytology was available for 101 patients; 66 symptomatic and 35 asymptomatic. Suspicious cytological findings were found in nine patients (14%) in the symptomatic group and 17 (49%) in the asymptomatic group. DNA flow cytometry was available for 49 patients (25 symptomatic, 24 asymptomatic), with aneuploidy detected in six patients (24%) in the symptomatic group and 15 (63%) in the asymptomatic group. Explanted liver histology showed biliary dysplasia or cholangiocarcinoma in 11 symptomatic patients (12%) and 15 asymptomatic patients (43%). A combination of cytological and DNA flow cytometry findings resulted in a test sensitivity of 68%, with a specificity of 86%. Ten-year survival in the asymptomatic group was 91%. CONCLUSIONS: Dysplasia surveillance using brush specimens may help to select those patients likely to benefit from early liver transplantation. It remains unclear as to whether surveillance with brush cytology improves long-term survival, but there is presently no better method with which to predict transplantation timing.

Surveillance of primary sclerosing cholangitis with ERC and brush cytology: risk factors for cholangiocarcinoma.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to bile duct strictures and fibrosis, and predisposing to cholangiocarcinoma (CCA). Biliary dysplasia is a known precursor of CCA. In our unit, PSC patients undergo regular surveillance with ERC and brush cytology (BC), and liver transplantation is an option in case with biliary dysplasia. We evaluated the risk factors for biliary dysplasia and CCA based on ERC imaging, BC and liver function tests. PATIENTS AND METHODS: Seven hundred and eighty-eight ERCs were performed with BC for 447 PSC patients. ERC images were evaluated using the modified Amsterdam score, neutrophilic inflammation was assessed in BC, and liver function tests were collected. Ploidy analysis with DNA flow cytometry was performed in cases with advanced PSC or previous suspicious BC/aneuploidy. The endpoint was either a benign disease course (follow-up for ≥2.4 years after the latest ERC), benign histology, biliary dysplasia or CCA. RESULTS: Benign disease course was seen in 424/447 (including 23 cases with biliary dysplasia), and CCA in 17 (3.8%) patients. Gallbladder carcinoma/carcinoma in situ was diagnosed in three patients. Advanced ERC findings, male gender, suspicious BC, aneuploidy in flow cytometry, inflammation, and elevation of ALP, bilirubin, ALT, AST, GGT, CEA and CA19-9 represented significant risk factors for CCA in univariate analysis. CONCLUSIONS: PSC patients with advanced bile duct disease and elevated liver enzymes, CEA or CA19-9, inflammation or suspicious BC are most likely to develop CCA. These patients may benefit from surveillance with BC if early liver transplantation is possible.

Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. PATIENTS AND METHODS: Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. RESULTS: PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. CONCLUSIONS: Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.

Outcome of inflammatory bowel disease patients treated with TNF-α inhibitors: two-year follow-up.

BACKGROUND: Biological medications, particularly TNF-α inhibitors, are used increasingly for active inflammatory bowel disease (IBD). Even though they are superior to many older medications in achieving remission and mucosal healing, primary nonresponse and loss of response remain significant problems, and a remarkable proportion of patients still need surgery at some point. OBJECTIVE: To study the outcome of IBD patients treated with TNF-α inhibitors, either infliximab or adalimumab, with a two-year follow-up. PATIENTS AND METHODS: Patient data from the hospital electronic patient documents of IBD patients treated with TNF-α inhibitors were studied. The main targets of interest were treatment response, the remission rate and the number of patients operated, as well as reasons for the discontinuation of treatment. Remission was defined both endoscopically and by faecal calprotectin. RESULTS: Altogether 100 patients were included. Only 29% of the patients achieved remission during the two-year follow-up. 26% of the Crohn's disease patients and 36% of the ulcerative colitis patients underwent surgery during the follow-up. A significant proportion of patients experienced side effects of the medication (21%) or discontinued the therapy for other reasons (altogether 63%). CONCLUSIONS: In this single centre study of 100 IBD patients treated with TNF-α inhibitors, less than one-third of the patients achieved remission, and a significant proportion had side effects and needed surgery during the two-year follow-up. There is an obvious need for more effective therapies with less side effects for IBD patients.

Does oral α-galactosidase relieve irritable bowel symptoms?

OBJECTIVE: Abdominal bloating is reported by a majority of irritable bowel syndrome (IBS) patients. Excess colonic fermentation may cause gaseous symptoms. Several foodstuffs contain oligosaccharides with an α-galactosidic linkage that is resistant to mammalian hydrolases. Assisted hydrolysis by exogenous α-galactosidase enzyme (AG) could offer a way of controlling IBS symptoms by reducing colonic fermentation and gas production. The aim of this study was to assess the effect of AG on symptom severity and quality of life in IBS patients with abdominal bloating or flatulence. METHODS: A total of 125 subjects with IBS received AG or placebo at meals for 12 weeks. IBS-Symptom Severity Score (IBS-SSS) and quality of life (QoL) were assessed at baseline, during the treatment and at 4-week follow-up. RESULTS: AG showed a trend toward a more prominent decrease in IBS-SSS. The responder rate at week 16 was higher for the AG group. No difference was detected in QoL between AG and placebo groups. A total of 25 patients (18 in AG group and 7 in placebo group, p = 0.016) withdrew from the study. Abdominal pain and diarrhea were more often reported as reason for withdrawal in AG group. CONCLUSIONS: We found no evidence to support the use of AG routinely in IBS patients. Improvement of clinical response at 4-week follow-up may suggest a long-term effect of unknown mechanism, but could also be attributed to non-responder drop out. Gastrointestinal (GI) side effects may be a coincidence in this study, but irritation of GI tract by AG administration cannot be excluded.

Health-related quality of life among patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: To assess health-related quality of life (HRQoL) of patients with primary sclerosing cholangitis (PSC), and to compare it with that of the general population. Also, to examine changes in HRQoL in newly diagnosed PSC patients at a follow-up 1-2 years later, and to compare their HRQoL with HRQoL of newly diagnosed inflammatory bowel disease (IBD) patients. Furthermore, sources of and need for disease-related information among PSC patients were surveyed. METHODS: Primary sclerosing cholangitis patients filled in the survey questionnaire when attending an endoscopic retrograde cholangiography examination. The 15D served as a general HRQoL instrument. The follow-up questionnaire was mailed to the newly diagnosed patients 1-2 years later. RESULTS: No significant difference was seen in 15D scores between PSC patients and general population, but the dimensions of excretion (P < 0.001), depression (P = 0.003), distress (P = 0.003) and vitality (P = 0.005) were significantly lower in PSC. Age and symptoms affected HRQoL but severity of biliary changes did not. Those with newly diagnosed IBD had lower 15D scores than those with PSC. No significant changes were observed in 15D scores of new PSC patients in the follow-up. Many patients were dissatisfied with information received. CONCLUSION: Newly diagnosed PSC patients have better HRQoL than do IBD patients, and no significant HRQoL changes were observed in the mean follow-up of 1.58 years after PSC diagnosis. ERC findings did not correlate with HRQoL or symptoms. HRQoL of PSC patients was mostly comparable with that of general population, but special attention should be paid to patients' psychological well-being.

Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case-control observational study based on registry data.

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR = 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.

The hidden epidemic: Uncovering incidental fatty liver disease and its metabolic comorbidities by datamining in a hospital data lake - A real-world cohort study.

AIMS: To identify individuals with incidental fatty liver disease (FLD), and to evaluate its prevalence, metabolic co-morbidities and impact on follow-up. METHODS: We leveraged the data-lake of Helsinki Uusimaa Hospital district (Finland) with a population of 1.7 million (specialist and primary care). A phrase recognition script on abdominal imaging reports (2008-2020) identified/excluded FLD or cirrhosis; we extracted ICD-codes, laboratory and BMI data. RESULTS: Excluding those with other liver diseases, the prevalence of FLD was 29% (steatosis yes/no, N=61,271/155,521; cirrhosis, N=3502). The false positive and negative rates were 5-6%. Only 1.6% of the FLD cases had the ICD code recorded and 32% had undergone full clinical evaluation for associated co-morbidities. Of the 35-65-year-old individuals with FLD, 20% had diabetes, 42% prediabetes and 28% a high liver fibrosis index. FLD was independently predicted by diabetes (OR 1.56, CI 1.46-1.66, p = 2.3 * 10^-41), BMI (1.46, 1.42-1.50, p = 1.7 * 10^-154) and plasma triglyceride level (1.5, 1.43-1.57, p = 3.5 * 10^-68). Alanine aminotransferase level mildly increased (1.12, 1.08-1.16, p = 2.2 * 10^-9) and high age decreased the risk (0.92, 0.89-0.94, p = 4.65*10^-09). Half of the cases had normal ALT. CONCLUSIONS: The incidental radiological finding of FLD is reliable and associated with metabolic risks but largely ignored, although it should lead to metabolic and hepatic follow-up.

Malignancies in patients with inflammatory bowel disease: a nationwide register study in Finland.

OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients.

Medication use among inflammatory bowel disease patients: excessive consumption of antidepressants and analgesics.

OBJECTIVE: Little is known about differences in the use of medications between inflammatory bowel disease (IBD) patients and the general population. The aims of this study were to observe those differences and to discuss reasons for them. The relation between medication use and HRQoL of IBD patients was examined. MATERIAL AND METHODS: The use of prescribed medication of 2831 IBD patients and 5662 control subjects were scrutinized and compared by utilizing a national reimbursement register. Annual costs and number of defined daily doses (DDD) of medications were calculated. The relationship between medications and health-related quality of life (HRQoL) of IBD patients was examined by using a postal questionnaire including a generic (15D) and a disease-specific (IBDQ) HRQoL tool. The questionnaire also included demographic questions and questions about IBD patients' use of biological medications. RESULTS: Use of antidepressants (OR: 1.44, 95% CI: 1.28-1.61), anxiolytics (OR: 1.52, 95% CI: 1.31-1.78), oral bisphosphonates (OR: 6.08, 95% CI: 4.56-8.11), cardiovascular medications (OR: 1.38, 95% CI: 1.24-1.54), antibiotics (OR: 4.01, 95% CI: 3.57-4.51), proton pump inhibitors (OR: 3.90, 95% CI: 3.48-4.36), and nonsteroidal anti-inflammatory analgesics (OR: 1.17, 95% CI: 1.07-1.28) was significantly more common in IBD than among the controls. Those who used antidepressants, anxiolytics, or analgesics had significantly impaired HRQoL (p < 0.001). CONCLUSIONS: IBD patients and general population differ in terms of their medicine use in many respects, and especially use of analgesics and antidepressants is more common among IBD patients. Use of antidepressants, anxiolytics, and analgesics was related to impaired HRQoL.

Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up.

OBJECTIVE: We assessed esophageal morbidity and relationships between surgical complications, symptoms, endoscopic findings, immunohistochemistry, and esophageal motility in adults with repaired esophageal atresia (EA). SUMMARY OF BACKGROUND DATA: There exist no previous population-based long-term follow-up studies on EA. METHODS: Participants were interviewed, and they underwent esophageal endoscopy and manometry. Matched control subjects (n = 287) served as controls. RESULTS: A total of 101 (42%) individuals representative of the entire study population participated at a mean age of 36 years (range, 21-57). Symptomatic gastroesophageal reflux had occurred in 34% and dysphagia in 85% of the patients and in 8% and 2% of the controls (P < 0.001 for both). Endoscopic findings included hiatal hernia (28%), Barrett's esophagus (11%), esophagitis (8%), and anastomotic stricture (8%). Immunohistochemistry revealed esophagitis in 25%, and CDX2-positive columnar epithelial metaplasia in 21%, with additional goblet cells and MUC2 positivity in 6%. Gastroesophageal reflux and dysphagia were equally common in individuals with normal histology, esophagitis, or epithelial metaplasia. Manometry demonstrated nonpropagating peristalsis in 80% of the patients, and low distal wave amplitudes of the esophagus in all the changes being significantly worse in those with epithelial metaplasia (P < or = 0.022 metaplasia vs. esophagitis/normal). Anastomotic complications (odds ratio [OR]: 8.6-24, 95% confidence interval [CI]: 1.7-260, P = 0.011-0.008), age (OR: 20, 95% CI: 1.3-310, P = 0.034), low distal esophageal body pressure (OR: 2.6, 95% CI: 0.7-10, P = 0.002), and defective esophageal peristalsis (OR: 2.2, 95% CI: 0.4-11, P = 0.014) predicted development of epithelial metaplasia. CONCLUSIONS: Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict development of epithelial metaplasia after repair of EA.

Societal costs for irritable bowel syndrome--a population based study.

OBJECTIVE: Irritable bowel syndrome (IBS) is associated with increased use of health care services. This study aims to estimate the costs of IBS in relation to differing diagnostic criteria of IBS, duration of symptoms, gender, and age. MATERIAL AND METHODS: A two-phase postal survey. Questionnaire I covering gastrointestinal (GI) symptoms by Manning and Rome II criteria was mailed to 5000 randomly selected adults. Questionnaire II, mailed to those fulfilling IBS criteria of Questionnaire I, recorded data on physician visits, medications, and diagnostic procedures performed. RESULTS: Proportion of GI consulters was 48% (95% CI 41-55%) and 32% (95% CI 28-36%) for Rome II and Manning groups. Annual GI related individual costs were euro 497 (95% CI euro 382-621) and euro 295 (95% CI euro 246-347) by Rome II and Manning criteria. Societal GI costs were euro 82 million and euro 154 million by Rome II and Manning criteria. Direct non-GI costs amounted to euro 43 million and euro 126 million by Rome II and Manning criteria. Duration of GI symptoms, gender, or age had no impact on GI costs. CONCLUSIONS: IBS incurs substantial GI and non-GI costs corresponding to a share of up to 5% of the national direct outpatient and medicine expenditures. The more restrictive Rome II criteria identify an IBS population incurring higher GI related individual costs than Manning criteria. Costs due to GI endoscopies are not lower for those with a long history of symptoms suggesting that guideline recommendations for avoiding repeated diagnostic procedures may not be followed.

Health-related quality of life in inflammatory bowel disease measured with the generic 15D instrument.

OBJECTIVES: In many surveys, inflammatory bowel disease (IBD) has been shown to have a negative impact on health-related quality of life (HRQoL), especially when the disease is active. The purpose of this study was to compare a disease-specific HRQoL tool (Inflammatory Bowel Disease Questionnaire, IBDQ) and a generic HRQoL tool (15D) in a large cohort of IBD patients, to assess the ability of the 15D to detect differences in HRQoL between disease states and to compare the HRQoL of IBD patients with that of the general population. METHODS: The study population comprised 2,931 IBD patients over 18 picked from a national Social Insurance Institute register and from a patient organization register. The 15D data for the general population came from the National Health 2000 Health Examination Survey. RESULTS: For patients with IBD, the 15D tool was feasible and had good discriminatory power. The total 15D score was significantly higher among patients with less active disease estimated by frequency of IBD symptoms and was strongly correlated with total IBDQ score. The general population scored significantly higher than did the study subjects on most of the 15D dimensions. CONCLUSIONS: The 15D was a fast and easy-to-apply method for the examination of HRQoL in IBD patients. In addition to HRQoL studies it could be used in everyday practice as well. Patients with IBD have worse HRQoL than do gender- and age-standardized controls.

Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C.

BACKGROUND/AIMS: The role of liver biopsy has been questioned in the management of patients with hepatitis C viral (HCV) infection. The aims of this study were to determine the impact of clinical parameters and degree of inflammation and steatosis on liver fibrosis. PATIENTS/METHODS: Clinical data and liver histology findings in 510 HCV patients were analysed. RESULTS: Hepatitis C virus genotype 1 (GT-1) was found in 38%, GT-2 in 15% and GT-3 in 45% of patients. In liver biopsy specimens, inflammation activity was present in 68%, increased fibrosis in 19% and marked steatosis in 17% of patients. Independent clinical risk factors for the increased fibrosis were patients' age at biopsy, body mass index (BMI) and duration of HCV. Steatosis and inflammation activity were independent histological risk factors for fibrosis only in GT-1; in GT-3, only inflammation correlated independently with fibrosis. CONCLUSIONS: Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in GT-1. When scoring liver biopsies of HCV patients, the degree of steatosis should be included in addition to fibrosis and inflammation activity.

Impact of demographic factors, medication and symptoms on disease-specific quality of life in inflammatory bowel disease.

OBJECTIVES: To investigate the relation of demographic factors, medication and symptoms to health-related quality of life in patients with inflammatory bowel disease, and to identify patients in need of special support. METHODS: A questionnaire packet comprising the Inflammatory Bowel Disease Questionnaire (IBDQ) and the European Federation of Crohn's and Colitis Associations' (EFCCA) Survey Questionnaire was sent to 3,852 adult members of the Crohn and Colitis Association of Finland. IBDQ was used for measuring health-related quality of life (HRQoL), and the EFCCA questionnaire gave information about demographics, symptoms and medication. RESULTS: Altogether 2,386 questionnaires (62%) were available for analysis. Patients reporting symptoms affecting leisure activities or work had significantly lower total IBDQ scores (indicating worse HRQoL) than patients with less disturbing symptoms. Satisfaction with current therapy, female gender and age affected the scores. Subjects who had undergone surgery scored lower than those who had not. Patients currently receiving corticosteroids and newly diagnosed patients had lower scores than other patients. CONCLUSIONS: In everyday practice, paying attention to and reducing patients' symptoms and their impact on daily life is important when aiming at improving HRQoL. Special attention should be given to patients who have undergone surgery, and to newly diagnosed patients.

Effect of smoking on gastric histology in Helicobacter pylori-positive gastritis.

OBJECTIVE: Smoking and Helicobacter pylori are both deleterious to the gastric and duodenal mucosa. Smoking also seems to modify inflammation in H. pylori infection. The aim of this study was to investigate the relationship between smoking and H. pylori in the Finnish population. MATERIAL AND METHODS: We analysed the effect of smoking on gastric inflammation, humoral response to H. pylori and peptic ulcer disease among 318 Finnish H. pylori-positive patients (age 18-75 years; 73 smokers). Gastric histology was evaluated according to the updated Sydney system. RESULTS: Smoking affected neither antral inflammation nor atrophy. In the gastric body, smokers showed milder chronic and neutrophilic inflammation and less atrophy (4% versus 17%, p=0.004). In smokers, H. pylori infiltration was denser in the atrium (mean 2.14 versus 1.87, p=0.02) but less dense in the body (mean 1.55 versus 1.84, p=0.003). Smoking thus seems to decrease inflammation in the gastric body and to delay atrophic changes in the gastric body. Subsequently, the prevalence of duodenal ulcers increased (32% versus 11%, p<0.001), but not the prevalence of gastric ulcers. Smoking also reduced serum IgG antibody titres against H. pylori (mean 8535 versus 5587, p=0.002) and their percentage decrease after successful eradication, possibly affecting serological diagnostic efficacy. Smokers were younger than non-smokers, but when age was taken into account, the differences remained the same. CONCLUSIONS: In H. pylori-positive gastritis, smoking reduced inflammation and atrophy in the gastric body as well as humoral response to H. pylori.

Symptoms, endoscopic findings and histology predicting symptomatic benefit of Helicobacter pylori eradication.

OBJECTIVE: To analyse factors predicting changes in dyspeptic symptoms after Helicobacter pylori eradication. MATERIAL AND METHODS: Of a total of 342 patients referred for upper gastrointestinal endoscopy at 23 centres in various parts of Finland, those tested positive for the rapid urease test were recruited in the study. Clinical and demographic data and data on dyspeptic symptoms (Gastrointestinal Symptoms Rating Scale) were collected via a structured questionnaire before and a year after the eradication therapy. Gastric biopsies were analysed according to the updated Sydney system. RESULTS: A total of 216 H. pylori-positive patients treated successfully with eradication therapy had complete data to be analysed. After the therapy, dyspeptic symptoms decreased by 29-32%. In a univariate analysis, it was found that duodenal ulcer, female gender, gastric antral neutrophilic inflammation, smoking and age from 50 to 59 years enhanced symptom improvement whereas atrophy in the gastric body reduced it. In a multivariate analysis, duodenal ulcer (odds ratio (OR) 3.2, 95% CI 1.3-7.8) and age from 50 to 59 years (OR 2.2; 95% CI 1.2-3.9) and antral neutrophilic inflammation (OR 1.9, 95% CI 1.1-3.3) were better predictors of symptomatic response. CONCLUSION: The symptomatic benefit from H. pylori eradication therapy was greatest among duodenal ulcer patients.