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Objective: To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients.Design: Cross-sectional study.Setting: A referral-based university hospital.Patients: Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease.Measurements: The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history.Results: Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics.Conclusions: Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients. [ABSTRACT FROM AUTHOR]

Objectives: Blood group antigens traditionally have been associated with a risk of developing peptic ulcer and gastric cancer. Helicobacter pylori is a bacterium associated with chronic active gastritis and ulcer disease, and its attachment to gastric mucosa was recently shown in vitro to be mediated by blood group Lewisb and H antigens. This study was designed to test the clinical relevance of this laboratory observation in patients undergoing endoscopy and gastric biopsy. Methods: Blood group phenotypes and gastric biopsies for H. pylori and histology were determined and correlated in 384 patients undergoing upper endoscopy. Blood from healthy blood donors was tested for the same blood group antigens and used as a control group. Results: The distribution of blood groups ABO, Lewis, Rhesus, and MN was similar among the patients undergoing endoscopy and a control group of 2369 healthy blood donors from the same geographic area. There was no correlation between H. pylori infection or the H. pylori-associated diseases, peptic ulcer or chronic active gastritis, with any blood group phenotype, including Lewisb, blood group O, or both. Conclusion: No in vivo correlation between H. pylori infection or disease and Lewisb or H antigen could be demonstrated. Moreover, patients with H. pylori infection and disease have a distribution of blood group antigens similar to a control population. [ABSTRACT FROM AUTHOR]

Background & Aims: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade., Methods: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection., Results: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001)., Conclusions: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Diagnostic procedures in inflammatory bowel diseases (IBD) serve to secure the diagnosis and to optimize treatment. Upon initial diagnosis endoscopy up to the terminal ileum is mandatory including multiple step biopsies. When diagnostic guidelines are followed and adequate clinical information is available, IBD will be correctly classified in about 80 to 90% of cases upon first examination. In contrast endoscopic studies are only of limited value in monitoring treatment. The decision if and when to perform endoscopy during exacerbation of disease must be an individual one. When disease activity is evaluated, a distinction must be made between degree of activity as reflected by laboratory parameters and severity of illness as reflected by the clinical presentation with abdominal complaints, fistulas, abscesses, etc. Distinct activity indices are useful in clinical studies to obtain an objective evaluation of activity and severity of disease. At clinical routine visits questions should not only concern the basic illness but also ask for quality of life and psychosocial status. Only a small number of laboratory tests are needed for basic diagnosis and follow-up. A small bowel enteroclysis should always be performed upon primary diagnosis of Crohn's disease and during the course of disease when there is suspicion of small-bowel involvement. Double contrast barium enema should be limited to special indications as incomplete colonoscopy e.g. due to stenosis or suspected fistula. Sonography is the primary investigation when complications are suspected. CT is useful as an adjunct or when the afore mentioned methods do not show clear findings. NMR is the procedure of choice for detection of pararectal fistulas and abscesses. Transrectal endosonography is comparably good but limited to the experience of the investigators and by patient's tolerability.

Introduction: The clinical significance of the sonographic finding "periportal hyperechogenicity", which is characterized by hard periportal echoes, is largely undetermined. This phenomenon has been reported in a large number of disorders, as well as in healthy persons., Methods: A prospective study of 1853 patients revealed this finding in 12 cases. These 12 patients were followed up after two to four months., Results: Only four cases were seen to still have diffuse periportal accentuation in the follow-up, while five patients showed a partially and three a completely normal liver. The laboratory values of these 12 patients were largely normal at the time of diagnosis and follow-up. Periportal accentuation was not correlated with any hepatological disorders. Examination using two different ultrasound devices revealed no major differences., Discussion: Overall, these findings confirm the earlier assumption that this sonographic picture designated as periportal hyperechogenicity or accentuation is not diagnostic of any hepatological disorder, nor is it even a sign of disease, because most patients with this phenomenon can be termed hepatologically "healthy".

Approximately 50% of patients with chronic hepatitis C respond to treatment with interferon-alpha. The aim of this randomized controlled trial was to evaluate whether an increase in dose of interferon-alpha augments response rate. One hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a three-month course of 3 MU IFN-alpha2b administered every two days. All patients were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was performed. Complete response was defined by normal serum ALT concentrations and disappearance of HCV-RNA. After three months, 60 nonresponders were randomized (stratified according to histology) either to continue 3 MU interferon-alpha2b every two days for another six months (group A, total dose: 410 MU) or to receive increasing doses of interferon-alpha2b (6 MU every two days for three months, followed by 10 MU every two days for three months) (group B, total dose: 870 MU). Serum ALT concentrations were measured monthly and HCV-RNA at three-month intervals. Liver biopsy was repeated six months after end of treatment. Pretreatment characteristics of the randomized patients were: group A: N = 30; male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT 108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years; CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of treatment six patients in group B but none in group A became responders [P = 0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were noncirrhotics. High-dose interferon was not tolerated by six patients in group B. Noncompliance resulted in five dropouts in group A and one in group B. During the six-month follow-up, four of the six responders relapsed. A patient in group A with increased serum ALT concentration but negative HCV-RNA at the end of treatment became a full responder after six months. Of nonresponders to 3 MU interferon alpha2b every two days for three months, 20% responded to higher interferon doses, but none to continued standard dose. Prolonged treatment with interferon may be necessary to obtain a sustained response. However, treatment with higher-dose interferon was not tolerated in 20% of the patients.

In previous studies measuring intragastric pH in healthy volunteers it was shown that there was a faster onset of action with ranitidine (CAS 66357-35-5) 300 mg effervescent tablets (Zantac) compared to standard tablets. In a single-centre, randomised, open cross-over study the pH-values obtained over 6 h following the administration of one ranitidine 150 mg effervescent tablet were compared with those after aluminium oxide-magnesium hydroxide (algeldrate, CAS 1330-44-5, Al-Mg-hydroxide) 10 ml and placebo in healthy volunteers. 24 healthy male subjects between 19 and 32 years of age entered the study, 19 subjects were available for all three measurements. After an overnight fast, intragastric pH was monitored for 7 h using a glass electrode and a digital data recorder. The time in % during which the pH was > or = 3.5 and the area under the curve of the obtained pH-curves were compared. There was a highly statistically significant difference between ranitidine effervescent tablets versus Al-Mg-hydroxide and placebo whereas there was no such difference between Al-Mg-hydroxide and placebo. The onset of action of ranitidine effervescent tablets was almost immediate. It is concluded that there was a clear superiority of ranitidine effervescent tablets in healthy volunteers and it is suggested that pH-metry in patients with acidity-related diseases should be investigated for a better understanding of the function of effervescent tablets.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The profile of risk factors associated with HCC includes not only chronic infection with hepatitis B virus and/or hepatitis C virus with subsequent cirrhosis, but also metabolic and alcoholic chronic liver diseases. While the risk of developing cancer is high in patients with cirrhosis, the aim of most screening programmes is to detect small, potentially resectable tumors. Serum alpha 1-fetoprotein lacks both sensitivity and specificity as a screening test and two-thirds of patients with small HCCs have levels below 200 ng/ml. Hepatic resection or liver transplantation at an early stage of HCC, without extrahepatic metastasis, provide complete cure of the disease.

Background: Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with early development of emphysema, liver cirrhosis, and hepatocellular carcinoma. The aim of the present study was to define prognosis and life expectancy in patients with alpha 1-antitrypsin deficiency with and without chronic liver disease., Methods: After a follow-up of 15 years the estimated life table analysis of mortality of 160 patients with alpha 1-antitrypsin deficiency was retrospectively calculated. The survival time was estimated using the Kaplan-Meier survival curves and was compared with the life expectancy of the age- and sex-matched population of west Austria., Results: Fifty-four patients with alpha 1-antitrypsin patients had evidence of chronic liver disease; of these, 78% showed positive viral markers. Of the 106 patients with alpha 1-antitrypsin deficiency without chronic liver disease none had evidence of additional viral infection. Life expectancy in patients with alpha-1 antitrypsin deficiency and chronic liver disease was significantly lower than in patients with alpha 1-antitrypsin deficiency without chronic liver disease (p = 0.001). No difference in life expectancy in alpha 1-antitrypsin deficiency without chronic liver disease was found in comparison with that of the normal population., Conclusions: We suggest that in alpha 1-antitrypsin deficiency-associated chronic liver disease it is the high coinfection rather than the inborn error of metabolism itself that is responsible for a deterioration of life expectancy or for the poor prognosis of the disease.

The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.

Aim: Reports in the literautre differ widely with regard to visualisation of the inferior mesenteric artery (IMA) by B-mode ultrasonography. Hence, our study aimed at obtaining exact data on the feasibility of visualising the inferior mesenteric artery via B-mode ultrasonography in a relatively large patient population., Method: At the outpatient department of gastroenterology and hepatology 51 males (aged 14 to 75 years) and 53 females (aged 16 to 79 years) were examined consecutively by two experienced investigators via B-mode scan within the overall framework of a routine screening programme, in each case after overnight fasting. Knowledge of normal anatomic conditions and of the possible variations of the IMA is mandatory for correct IMA visualisation., Results: We succeeded in visualising the IMA via B-mode scan in 41 of the 51 males (80.39%) and in 40 of the 53 females (75.47%), i.e. in a total of 81 of 104 patients (77.88%) in 2-3 cm length., Conclusion: The results show that IMA can be visualised by B-mode ultrasonography in a manner comparable to visualisation of the superior mesenteric artery (82). This is an essential finding, since duplex sonography of the IMA yields important information on disease activity in inflammatory bowel disease, and B-mode scanning of the IMA is the prerequisite for duplex scanning.

Hepatocellular adenomatosis is characterized by the presence of numerous (arbitrarily > 10) adenomas within an otherwise normal liver without a history of glycogen storage disease or steroid hormone therapy. Although the disease is rare, its importance lies in its tendency to produce symptoms such as abdominal pain and its potential for abdominal hemorrhages. However, the prognosis of hepatocellular adenomatosis remains uncertain. Here we describe the case of a 40-yr-old female with hepatocellular adenomatosis without evidence of serious complications, who was observed over a period of 11 yr.

Objective: To determine the therapeutic efficacy and safety of three doses of olsalazine compared with the standard dose of sulphasalazine., Design: Randomized double-blind multicentre 6-month study comparing three doses of olsalazine (0.5, 1.25 and 2.0 g daily) and sulphasalazine 2.0 g daily for maintaining remission in patients with ulcerative colitis., Setting: Public hospitals and private practices in Germany, Austria and Switzerland., Patients: A total of 162 patients with ulcerative colitis in remission., Results: According to intention-to-treat analysis, the failure rates of the different treatment groups were not significantly different (36, 49 and 24% for 0.5, 1.25 and 2.0 g olsalazine daily and 32% for 2.0 g sulphasalazine daily). Olsalazine and sulphasalazine showed a tendency towards lower failure rates in extended (28%) than in distal disease (44%). The withdrawal rate due to adverse effects was 4%, the most frequent single event being diarrhoea (2.5, 5.2 and 11.7% for 0.5, 1.25 and 2.0 g olsalazine daily and 0% for sulphasalazine daily)., Conclusion: This study found no significant differences between the therapeutic efficacy or safety of 0.5-2.0 g olsalazine daily. Because of its sulpha-free formulation olsalazine may, however, be preferred to sulphasalazine.

Wilson's disease is a lethal defect in copper metabolism causing a continual increase in tissue copper concentrations that become toxic to the liver, brain, kidney, eye, skeletal system, and several other tissues and organs. The liver is unique among these in being both the site of the etiologic biochemical abnormality and the organ that is always affected by copper toxicosis. Although myocardial muscle involvement has been reported in association with Wilson's disease, copper deposits in peripheral muscle tissue have not yet been described. A case of a young patient with Wilson's disease who developed recurrent episodes of acute rhabdomyolysis is presented, and the accumulation of copper in muscle tissue as a possible complication is discussed.

Increased activation of lymphocytes in inflammatory bowel disease is reflected by alterations of various immunological functions including enhanced spontaneous secretion of rheumatoid factor by mononuclear cells. since in rheumatic diseases increased secretion of rheumatoid factor is associated with decreased levels of beta-endorphin in circulating blood mononuclear leukocytes, we investigated levels of leukocyte beta-endorphin in inflammatory bowel disease and compared them with those in hepatobiliary disorders and in healthy subjects. Levels of beta-endorphin were measured in extracts from peripheral blood mononuclear leukocytes by radioimmunoassay. beta-Endorphin levels ranged from 0 to 67 pg/10(6) cells. Mononuclear leukocytes from ulcerative colitis patients contained as much beta-endorphin as those from healthy control subjects. In patients with Crohn's disease, levels of beta-endorphin were reduced by as much as roughly 50%. An inverse relationship was found between leukocyte beta-endorphin on the one hand and erythrocyte sedimentation rate, blood granulocyte or thrombocyte counts, and C-reactive protein levels in plasma on the other. In patients with various hepatobiliary disorders including fatty liver disease, viral hepatitis, primary biliary cirrhosis, and cryptogenic or alcoholic cirrhosis, beta-endorphin levels were not significantly different from the normal range values. Data indicate that leukocyte beta-endorphin may be involved in regulation of the systemic inflammatory activity of Crohn's disease.

The importance of hepatitis C virus (HCV) infection as a cause of chronic liver disease has become clear with the introduction of serologic detection methods. On the basis of epidemiologic evidence the parenteral way of infection has been considered to be the most important one. However, the epidemiologic data regarding the significant route of infection are still limited. To study the ways of HCV-infection and their possible influence on the course of the disease, 73 patients with chronic hepatitis C infection were examined. Setting was the out-patient department of Gastroenterology of our University Hospital. Patients history, completed by a questionnaire, laboratory findings and liver histology were analysed. The study indicated that in 50% of the patients transmission had occurred through parenteral infection, the other 50% had been infected through the non-parenteral (sporadic) way. The study revealed further that the way of infection has an influence on the progression of liver disease with the patients infected sporadically showing histologically more serious hepatic changes. In 50 patients HCV-infection was the only cause of their chronic liver disease, in 23 patients additional pathogenic factors were detected. These 23 patients showed a rapid progress of the disease. Therefore, HCV-infection cannot be considered any longer as a disease that is primarily transmitted parenterally. Due to the large number of sporadic infections, HCV-infection will continue to be of great epidemiologic importance even after the effective elimination of contaminated blood products.

Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with premature development of emphysema, liver cirrhosis and hepatocellular carcinoma. This article reviews the existing literature on alpha-1-antitrypsin deficiency, with an emphasis on recent developments. A description of the protein, gene structure and function of alpha-1-antitrypsin as well as clinical aspects are presented. Treatment issues are addressed and a framework for the diagnostic workup and management of patients with alpha-1-antitrypsin deficiency and chronic liver disease is provided.

The diagnosis of gastric lymphoma in endoscopic biopsy specimens remains difficult despite the emergence of accepted criteria for the histologic diagnosis of lymphomas originating from mucosa-associated lymphoid tissue (MALT). The sensitivity and validity of immunoglobulin (Ig) gene rearrangement analysis of mucosal biopsies for the diagnosis of malignant B-cell lymphoma were investigated in comparison with conventional histology and immunohistology. Biopsy specimens from 34 different endoscopies of 20 patients with a previous history, or tentative diagnosis of gastric lymphoma, and 12 control samples were analyzed for the presence of clonal Ig gene rearrangements. A clonal B-cell population was detected by Southern blot analysis in all patients with a definitive histologic diagnosis of lymphoma. In addition, in two patients the detection of clonal rearrangements in biopsy specimens preceded by several months the histologic diagnosis of lymphoma, and clonality was confirmed in three further patients where histology remained inconclusive. In some cases of low-grade MALT-lymphoma, discrete spreading of malignant cells within chronically inflamed mucosa was suggested by the presence of identical clonal rearrangements in all simultaneously obtained biopsies, with or without histologically detectable involvement by lymphoma. Our results show that immunoglobulin gene rearrangement studies of endoscopic biopsy samples are an additional powerful tool for the diagnosis of gastric lymphoma, especially for detecting early recurrence, and improve the preoperative assessment of the extent of mucosal involvement.

The aim of the present study was to investigate prognosis and life expectancy in patients with primary biliary cirrhosis. We retrospectively analysed 59 patients from western Austria over 15 years (mean 6 years). The results of the present study were compared with the average life expectancy of the population of western Austria and with the results of the Mayo study published in 1989. The mean survival time in our study was 112.7 months, 25% were dead by 132 months. Kaplan-Meier analysis showed a 95% probability to survive 1 year and a 84% probability to be alive at 5 years. Asymptomatic patients had a significantly better prognosis than symptomatic patients. In comparison with the Mayo study the patients in our study had a better prognosis and in comparison with the normal population a significantly worse life expectancy.

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.

Impaired blood clotting precludes percutaneous liver biopsy for histologic examination of liver tissue. The transjugular or laparoscopic approach are ways to reduce the risk of bleeding. These techniques, however, are laborious and confined to specialized centers. Methods of plugging the needle track with sealant presented so far are hampered by the need to leave either the cannula in situ or the need for a second percutaneous approach for the application of the sealant. We have tested a combined plugging-biopsy device allowing to perform the biopsy as a one-step procedure in patients with impaired clotting under laparoscopic vision control. In 37 patients either a modified Trucut or Menghini needle was tested. Handling of the Trucut needle proved easier. Tissue yield was satisfactory with both needles. Only one episode of bleeding was observed with a prototype Menghini needle. We conclude, that the combined plugging-biopsy device is a safe and reliable tool for obtaining liver tissue in patients with impaired blood coagulation.