Anna-Liisa Karvonen

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo‐controlled trial

No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC‐like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo‐controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases γ‐glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (−337 ± 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (−0.50 ± 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long‐term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated. (HEPATOLOGY 2004;40:1379–1386.)

A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid

BACKGROUND/AIMS Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. RESULTS There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. CONCLUSIONS These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.

Prevalence and incidence of primary biliary cirrhosis are increasing in Finland.

Objective. To examine the epidemiology of primary biliary cirrhosis (PBC) in Finland and to evaluate whether the possible increase in prevalence was attributable to the increasing incidence, better survival, or both. Material and methods. The Hospital Discharge Register, pathology registers, and death certificates for the years 1988–99 were scrutinized, and the patients identified were followed-up for survival until 31 October 2004. The study area covered four university hospital districts: a total of 25 hospitals. The diagnosis of PBC was regarded as definite (or probable) if three (or two) of the following criteria were fulfilled: positive antimitochondrial antibodies, constantly elevated alkaline phosphatase, and compatible liver histology. Results. In the total population of the study areas, the age-standardized prevalence of PBC increased during the study period from 103 (95% CI: 97–110) to 180 (172–189) per million inhabitants. Incidence increased from 12 (10–14) to 17 (15–20) per million inhabitants per year. The annual average increase in prevalence was 5.1% (4.2–5.9%, p<0.0001) and in incidence 3.5% (0.9%–6.0%, p=0.008). In gender-specific analyses among women, the prevalence of PBC increased from 161 (151–171) to 292 (277–207) per million during the study period and the incidence from 20 (16–24) to 27 (23–32) per million per year. The death rate was 4% per year and half the deaths were from liver-related causes. Survival after diagnosis during the study period lengthened. Conclusions. The prevalence of PBC increased in Finland during 1988–99, owing to both the increased incidence and the prolonged survival.

Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy

BACKGROUND We investigated whether individuals with positive coeliac disease antibodies but without small-bowel villous atrophy have mucosal inflammation implicating gluten-sensitivity. METHODS Small-bowel mucosal morphology; CD3+, alphabeta+, and gammadelta+ T-cell receptor-bearing intraepithelial lymphocytes; and mucosal HLA-DR expression were studied in 96 IgA-class antireticulin or antigliadin antibody-positive adults suspected of having coeliac disease and in 27 control subjects. RESULTS Villous atrophy compatible with coeliac disease was found in altogether 29 patients, in 18 of 21 (86%) patients with both antireticulin and antigliadin antibodies, in 9 of 15 (60%) patients with antireticulin antibodies only, and in 2 of 60 (3%) with antigliadin antibodies only. In 67 antibody-positive patients with normal villous architecture the densities of CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes were significantly higher than in non-coeliac control subjects. Ten patients with initially increased densities of gammadelta+ T cells but normal villous structure underwent a follow-up biopsy after 4-18 months, which showed villous atrophy in five patients. CONCLUSIONS IgA-class antireticulin or antigliadin antibody-positive patients with normal small-bowel mucosal morphology frequently have immunohistochemical markers of coeliac disease latency. Together with our follow-up data this implies that they may be gluten-sensitive.

Mortality in ulcerative colitis and Crohn's disease. A population-based study in Finland ☆

BACKGROUND An increased mortality has been reported in patients with Crohns disease (CD), while figures have remained similar or decreased in patients with ulcerative colitis (UC) compared to the population in general. We evaluated the long-term mortality risk of patients with inflammatory bowel diseases (IBD) in a well-defined population. METHODS The data were based on a prospective IBD register in our catchment area; follow-up covered 1986-2007. The population based cohort comprised 1915 adult patients, 1254 with UC, 550 with CD, and 111 with inflammatory bowel disease unclassified (IBDU). The mortality rate and causes of death were obtained from Statistics Finland. RESULTS We recorded 223 deaths among the 1915 patients with IBD within a follow-up of 29,644 person-years. The standardised mortality rate (SMR) was 1.14 in CD and 0.90 in UC. In cause-specific mortality; the risk of death in diseases of the digestive system was significantly increased in CD (SMR 5.38). The mortality in colorectal cancer was non-significantly increased in both UC and CD (SMR 1.80 and 1.88, respectively). Compared to the background population, there were significantly fewer deaths due to mental and behavioural disorders due to use of alcohol (0 observed, 10.2 expected in IBD). CONCLUSIONS The overall mortality in CD and CU was not different from that in the population. In cause-specific mortality, diseases of the digestive system were significantly increased. Deaths due to mental and behavioural disorders resulting from alcohol consumption were less common in patients with IBD than in the population at large in Finland.

The epidemiology of inflammatory bowel diseases in Finland

Abstract Objective. There is evidence that the incidence of inflammatory bowel diseases is increasing, but the data are inconsistent. For appropriate allocation of health care resources, knowledge of the actual occurrence of diseases is important. We here conducted an epidemiological survey using a population-based register in a well-defined area representative of the whole Finnish population. Material and methods. The collection of cases took place in 1986–1999 in the Tampere region, which comprised 363,000 adults in 1999. All municipal centers detecting and managing inflammatory bowel diseases participated in the study. Particular effort was made to register all cases. Results. The total number of patients was 1691. The prevalence per 100,000 inhabitants in 1986 was 119 for ulcerative colitis (UC), 40 for Crohns disease (CD) and 9 for inflammatory bowel disease unclassified (IBDU); in 1999 the respective figures were 291, 124 and 27. During the study period, the annual incidence of UC increased from 13.3 to 19.6 per 100,000, and that of CD from 5.0 to 9.4, whereas the incidence of IBDU decreased from 1.2 to 0.3. The extent of the diseases remained by and large unaltered over the time of survey. Conclusions. An increasing trend was observed in the number of patients with inflammatory bowel disease, and the frequency was higher than that reported in most surveys. This increase constitutes a challenge for the health care system.

Comparison of three stool antigen tests in confirming Helicobacter pylori eradication in adults

Objective Reliable and readily available non-invasive methods are needed for detection of Helicobacter pylori infection and assessment of eradication therapy. In H. pylori-positive subjects we compared three stool antigen tests (Premier Platinum HpSA, Amplified IDEIA HpStAR and ImmunoCard STAT!HpSA) with invasive tests before their eradication therapy, and with non-invasive diagnostic methods after their therapy. Material and methods A total of 82 adults with dyspepsia (aged 24–79 years) with an H. pylori-positive rapid urease test were enrolled in the study. Before therapy, H. pylori status was also confirmed with histology, culture and serology. After eradication, success was assessed with the [13C]-urea breath test (UBT) and usually also with serology. Results At baseline, sensitivities of these stool antigen tests were 90.2% for HpSA, 97.6% for HpStAR and 96.3% for ImmunoCard. Eradication therapy was successful in 66 patients and unsuccessful in 16. Sensitivity and specificity of the three stool antigen tests in the post-eradication setting were, respectively, 75.0% and 95.5% for HpSA, 93.8% and 98.5% for HpStAR and 87.5% and 95.5% for Immunocard. Conclusions The performance of all three stool antigen tests in the post-treatment setting was slightly inferior to that of the UBT test and serology, with monoclonal antibody-based tests showing better results.

The risk of colorectal cancer in patients with inflammatory bowel diseases in Finland: a follow-up of 20 years.

BACKGROUND AND AIMS Data on the relative risk of colorectal cancer in inflammatory bowel diseases (IBD) are inconsistent. To prevent the development of cancer, endoscopic facilities should be targeted correctly. We report here the results of a 20-year follow-up in Finland and evaluate the efficacy of endoscopic surveillance in cancer prevention. METHODS The data were based on an IBD register in our catchment area in 1986-2007. The population-based cohort comprised 1915 patients, 1254 with ulcerative colitis, 550 with Crohns disease and 111 with inflammatory bowel unclassified. Colorectal cancer cases were obtained from the IBD register; the colorectal cancer figures in the respective population were obtained from the Finnish Cancer Registry. RESULTS Colorectal cancer was found in 21 patients, the standardized incidence ratio (SIR) being 1.83 (95% confidence interval (CI) 1.13-2.79) for IBD. Colorectal cancer risk was 3.09 (CI 1.50-5.75) for extensive UC, and 3.62 (CI 2.00-11.87) for Crohns disease affecting the colon. Eleven (52%) of the colorectal cancer cases were TNM stage 3 or 4. In the same observation period 10 colectomies with ileoanal anastomosis were performed with the indication of cancer risk in ulcerative colitis; of these 10 patients only two had no additional risk factors for colorectal cancer, for example primary sclerosing cholangitis, pseudopolyposis or active disease. CONCLUSIONS The risk of colorectal cancer in the cohort was only moderately increased. In the absence of additional risk factors, endoscopic surveillance was of limited benefit. We therefore suggest intensive endoscopy surveillance to be targeted on patients with definite risk factors.

Ascites: Aetiology, mortality and the prevalence of spontaneous bacterial peritonitis

Objective. To assess the aetiology, prognosis and prevalence of spontaneous bacterial peritonitis (SBP) in patients hospitalized for ascites. The validity of an elevated (>11 g/l) serum-ascites albumin gradient (SAAG) in the diagnostic work-up was evaluated. Mortality trends were observed over two periods of time. Material and methods. A total of 231 consecutive patients who underwent diagnostic paracentesis between February 1994 and December 1998 and January 2005 and March 2007 were included in the study. The definition of SBP comprised polymorphonuclear cell count >250/mm3 without evidence of other intra-abdominal source of infection. SAAG was obtained and the Child-Pugh classification applied. Survival rates were obtained from medical records. Results. The most common causes of ascites were alcohol liver cirrhosis (n=143; 62%), malignancy (n=30; 13%), non-alcoholic cirrhosis (n=11; 5%) and malignancy with cirrhosis (n=11; 5%). The prevalence of SBP in cirrhosis was 6.7% (95% CI 2.8–10.5%). Overall mortality rates at 1 month, 6 months and 1 year were 22%, 40% and 48%, respectively, and remained unchanged between the intervals. Patients with grade C liver disease had higher 1-month (26% versus 6%), and 6-month (44% versus 27%) mortality rates than grade B patients, but commensurate 1-year mortality (49% versus 47%). SAAG was ≥11 g/l in 85% of patients with obvious portal hypertension and in 30% with malignancy, ascites albumin level ≤9 g/l in 69% and 20%, respectively. Conclusions. Mortality in patients with ascites was high. The occurrence of SBP was relatively low in our series, with a high proportion of alcoholic cirrhosis. SAAG was inaccurate in differentiating ascites caused by portal hypertension or malignancy.

Factors predicting interferon treatment response in patients with chronic hepatitis C: late viral clearance does not preclude a sustained response

OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of interferon in chronic hepatitis C (HCV), predictors have been sought to detect patients with a good treatment response. Also, markers for determining a poor response early in the course of therapy, such as the lack of early viral clearance, have been proposed. METHODS: Ninety-seven patients with chronic hepatitis C were enrolled to receive leukocyte α-interferon according to a stepped-care management protocol. The final virological treatment response was evaluated in 74 patients after a 6-month post-treatment follow-up. The relationship between pretreatment and during-treatment variables and the long-term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment ALT levels, and lower γ-glutamyl transferase (GGT)/ALT ratios and GGT as well as younger age were significantly associated with a sustained response; a trend was also detected for lower serum ferritin levels. Normalization of ALT by 3 months was also a significant predictor of a long-term response. Of the 27 patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at 6 months. Of these patients, however, five (19%) still achieved a sustained virological response after treatment for up to 12 months. CONCLUSIONS: In contrast to some previous reports, our results suggest that a late viral clearance after 6 months of interferon monotherapy may not preclude a favorable long-term response after a 12-month treatment, especially in patients carrying a non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good treatment response.