Göran Bodemar

Long-term follow-up of patients with NAFLD and elevated liver enzymes.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long‐term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy‐proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow‐up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver‐related (P = .04) causes. Seven patients (5.4%) developed end‐stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver‐related complications. At follow‐up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow‐up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end‐stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain. (HEPATOLOGY 2006;44:865–873.)

Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases.

AIMS To investigate whether hyperechogenicity of liver can reliably be interpreted as liver steatosis and if any concomitant or isolated fibrosis can be disclosed. PATIENTS AND METHODS A series of 165 patients with no signs or symptoms of liver disease referred because of slightly to moderately raised aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7-5.0 microkat/l) for more than 6 months were prospectively investigated with a comprehensive laboratory profile, ultrasound examination of liver and percutaneous liver biopsy Fibrosis was assessed quantitatively and according to Metavir. Steatosis was graded as none, mild, moderate or severe. RESULTS Of 98 (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at least moderate degree, 9 patients with same degree of steatosis had normal echogenicity and 13 patients with no or only mild steatosis had a hyperechogenic liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87, negative predictive value 0.87). About the same relations were found regardless of body mass index and degree of fibrosis. With increased echogenicity together with high attenuation (n = 591 and reduced portal vessel wall distinction (n = 79), positive predictive value increased to 0.93 and 0.94, respectively. Quantitatively assessed fibrosis (mean +/- SD) was 3.2 +/- 4.6% of biopsy area with normal and 2.3 +/- 1.8% with raised echogenicity (ns). Echogenicity was normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients with cirrhosis. Any structural, non-homogenous findings at ultrasound were not associated with architectural fibrotic changes and none had nodular contours of liver surface. CONCLUSIONS Assessment of liver echogenicity is of value for detection or exclusion of moderate to pronounced fatty infiltration (correct classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even cirrhosis in asymptomatic patients with mild to moderately elevated liver transaminases.

The Clinical Significance of Slightly to Moderately Increased Liver Transaminase Values in Asymptomatic Patients

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients.

Treatment with cimetidine, antacid, or placebo in patients with dyspepsia of unknown origin.

Patients with dyspepsia of unknown origin were randomly allocated to a controlled double-blind study to examine the symptomatic effect of cimetidine and antacid especially on the relief of pain, nausea, and bloating. Two hundred and twenty-two patients with no previous history of peptic ulcer disease and no evidence of other organic causes of dyspepsia were treated for 6 weeks with placebo, cimetidine, or antacid. The results showed that cimetidine was superior to both placebo and antacid in relieving pain and nausea but not bloating. Certain background factors, such as epigastric pain and symptoms relieved by solid food, had a significant positive influence on the outcome of treatment. When the impact of background factors was taken into account, cimetidine was found to be more effective than both placebo and antacid also with regard to the number of patients who improved in general well-being.

Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease.

Objective. Moderate alcohol consumption has been reported to be inversely associated with cardiovascular disease and total mortality. The importance of non-alcoholic fatty liver disease (NAFLD) is increasing and many NAFLD patients suffer from cardiovascular disease. In these patients, moderate alcohol consumption could be beneficial. The aim of this study was to investigate whether low alcohol intake, consistent with the diagnosis of NAFLD, is associated with fibrosis progression in established NAFLD. Material and methods. Seventy-one patients originally referred because of chronically elevated liver enzymes and diagnosed with biopsy-proven NAFLD were re-evaluated. A validated questionnaire combined with an oral interview was used to assess weekly alcohol consumption and the frequency of episodic drinking. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of endstage liver disease during follow-up. Results. Mean follow-up (SD) was 13.8 (1.2) years between liver biopsies. At follow-up, 17 patients (24%) fulfilled the criteria for significant fibrosis progression. The proportion of patients reporting heavy episodic drinking at least once a month was higher among those with significant fibrosis progression (p=0.003) and a trend towards higher weekly alcohol consumption was also seen (p=0.061). In a multivariate binary logistic regression analysis, heavy episodic drinking (p<0.001) and insulin resistance (p<0.01) were independently associated with significant fibrosis progression. Conclusions. Moderate alcohol consumption, consistent with the diagnosis of NAFLD to be set, is associated with fibrosis progression in NAFLD. These patients should be advised to refrain from heavy episodic drinking.

Effect of omeprazole, a substituted benzimidazole, on 24-h intragastric acidity in patients with peptic ulcer disease.

Intragastric pH was measured during physiological conditions over 24-h periods in patients with peptic ulcer disease. After single oral doses of 20, 40, and 80 mg omeprazole we found a dose-dependent reduction in mean intragastric acidity ranging from 38% to 99%. After treatment for 1 week with omeprazole, 40 mg daily, with or without an initial loading dose of 80 mg, intragastric acidity was decreased by more than 99%. This is a more pronounced decrease in acidity than can be achieved even with very high doses of histamine H2-receptor antagonists.

Treatment of anaemia in inflammatory bowel disease with iron sucrose

BACKGROUND Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. METHODS Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 +/- 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of > or = 20 g/L or to normal haemoglobin levels (> or = 120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. RESULTS Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 +/- 85 (4-291) (mean +/- s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. CONCLUSIONS Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.A. Kasprzak, W. Biczysko, A. Adamek, J. Wysocki, M. Zabel, D. Jurczyszyn, M. Chmielewski & J. Surdyk-Zasada Depts. of Histology and Embryology, Clinical Pathology and Health Prophylaxis, and the Chair of Gastroenterology and Human Nutrition, Poznan University of Medical Sciences, Poznan, Poland; Ward of Infectious Diseases, J. Strus ́ Hospital, Poznan ́, Poland; Dept. of Histology and Embryology, University of Medical Sciences in Wroc aw, Poland

Histologic Changes in the Gastroduodenal Mucosa after Long-Term Medical Treatment with Cimetidine or Parietal Cell Vagotomy in Patients with Juxtapyloric Ulcer Disease

Biopsy specimens were collected during endoscopy from pre-established sites in the corpus (n = 60), antrum (n = 53), and the duodenal bulb (n = 54) from the same patient before and 2-3 years after parietal cell vagotomy (PVC) or after a similar period of treatment with cimetidine. There was a significant increase in scores of chronic body gastritis after PCV (p less than 0.001) even in comparison with the cimetidine group (p less than 0.01), for which the scores of chronic body gastritis remained essentially unchanged. The scores of chronic antral gastritis and the incidence of intestinal metaplasia of the antrum increased significantly (p less than 0.05) in both the PCV and the cimetidine groups when the two treatment groups were analyzed together. The degree of polymorphonuclear infiltration in the body and antral mucosa, the incidence and severity of duodenitis, and the incidence of gastric metaplasia in the duodenal cap were unaffected by the treatment. In contrast to maintenance treatment with cimetidine PCV seems to accelerate the development of chronic body gastritis. The kappa statistics, as indicator of the reproducibility of histopathologic scoring, were acceptable.

Division of the Irritable Bowel Syndrome into Subgroups on the Basis of Daily Recorded Symptoms in Two Outpatient Samples

BACKGROUND If subgroups exist in a sample of patients with irritable bowel syndrome (IBS), they may represent different etiologic and pathophysiologic entities. Our aim was to identify subgroups on the basis of symptoms in IBS. METHODS Two independent groups of 56 (sample I) and 52 (sample II) outpatients recorded their abdominal symptoms daily for 6 weeks and 1 week, respectively. The daily records were assessed by using cluster analysis. RESULTS Similar subgroups appeared in both samples. Three bowel habit subgroups were identified. The first was distinguished by hard stools, varying stool consistency, and highly disturbed stool passage, the second by loose stools and urgency, and the third by normal stools and the least disturbed stool passage. Two pain/bloating subgroups were identified, one distinguished by little and the other by considerable pain and bloating. No relation was found between pain/bloating and bowel habit subgroup membership. Most patients had stool frequency within the normal range regardless of subgroup. In sample I the subgroups had stable symptoms during the study, and subgroup placement was not related to the presence of dyspepsia, smoking habits, or use of bulk agent and/or sporadic intake of loperamide. The degree of pain and bloating was inversely related to illness duration. CONCLUSIONS Subgroups exist in IBS. Division of IBS into bowel habit subgroups should be based on stool consistency, not frequency. Mechanisms mediating pain and bloating may be different from those mediating symptoms at defecation.

The Clinical Relevance of Endoscopic and Histologic Inflammation of Gastroduodenal Mucosa in Dyspepsia of Unknown Origin

Two hundred and ten patients were defined as having dyspepsia of unknown origin. At endoscopy 11% had body gastritis, 46% antral gastritis, and 19% bulbitis (two thirds combined with antral gastritis). Histologically, 22% had chronic corpus gastritis (79% superficial, 21% atrophic), which was combined with chronic antral gastritis in 84%, 33% had chronic antral gastritis (82% superficial, 18% atrophic); and 14% had duodenitis, which was combined with antral gastritis in 65%. Polymorphonuclear leukocytes were found in specimens from the body mucosa in 6%, from the antral mucosa in 13%, and from the duodenal cap in 4%. The endoscopic findings correlated significantly with the histologic findings in the duodenal bulb (kappa = 0.33) but not in the stomach. The frequency of endoscopic antral gastritis and the frequency of histologic chronic body and antral gastritis increased with age. Endoscopic bulbitis and histologic duodenitis and gastric metaplasia were commoner in men than in women. Peak acid output was higher in patients with than in those without endoscopic bulbitis and higher in smokers than in non-smokers when the significant sex differences in peak acid output were taken into account. Gastric metaplasia of the bulb was predominantly correlated to higher peak acid output and to some extent also to sex and smoking. Episodic pain was correlated to histologic duodenitis. Other dyspeptic symptoms and the intragastric bile acid concentration were not associated with any endoscopic or histologic findings. Of the 210 patients, 172 were reexamined after a double-blind 6-week treatment period with cimetidine, antacid, or placebo. The symptomatic outcome of these treatments was not associated with any significant change in endoscopic or histologic findings.