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Biomedical subjects

K P Maier

Publications and source records attributed to K P Maier.

At least 19 recordsLinked to original sources
PubMed1999

Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy. METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry. RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed. CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.

Administration, Oral↗
PubMed1998

[Necrotizing hepatitis after taking herbal remedies].

HISTORY AND CLINICAL FINDINGS: Two unrelated women, aged 39 and 42 years, had been admitted (at different times) to hospital because of "recurrence of an aetiologically uncertain acute hepatitis". Both patients had a history of acute hepatitis with GPT concentration of 796 and 755 U/l, respectively. Each of them had experienced recurrences of hepatitis, each of them preceded by taking herbal remedies as alternative medication, containing kava or common (or lesser) celandine, respectively. In each patient physical examination had been unremarkable. INVESTIGATIONS: Maximal values of GPT in the two patients were 422 and 350 U/l, respectively. Viral, autoimmune and metabolic causes of the hepatitis were excluded. In each of them liver biopsy revealed the picture of acute necrotizing hepatitis. DIAGNOSIS, TREATMENT AND COURSE: As it was suspected that the hepatitis was medication-induced, the intake of the mentioned herbal preparations was stopped. The liver function tests quickly became normal. CONCLUSION: In view of the rapid response to their withdrawal, a causal connection between intake of the herbal preparations and the recurrences of acute hepatitis is the most likely explanation in both cases.

Acute Disease↗
PubMed1998

[Cirrhosis of the liver as a precancerous condition].

Cirrhosis of the liver can be regarded as premalignant state, since more than 80 percent of hepatocellular carcinoma (HCC) in the western world develop in a cirrhotic liver. The risk to develop this malignancy depends on the activity of the underlying cirrhosis, its etiology and the duration of the disease. Patients suffering from cirrhosis of the liver due to HBV-, HCV- or HDV-infection and patients with genetic hemochromatosis exhibit a high risk for HCC. This risk is further increased by cocarcinogens, such as alcohol, nicotine and toxins. Ultrasound and AFP-studies aim to diagnose HCC early. The sensitivity of AFP in the serum is remarkably low (about 64%). In contrast a normal AFP-concentration (< 20 ng/ml) carries a high negative prognostic value (> 90%). Patients suspected to suffer from HCC according to the results of screening procedures should be subjected to additional radiologic investigations, such as CT-arterioportography or lipiodol-angiography.

Humans↗
PubMed1998

[Hepatocellular carcinoma: interdisciplinary treatment concept].

In most cases hepatocellular carcinoma develops in a cirrhotic liver. The stage of the cirrhosis and the number and size of the liver tumors are decisive for the prognosis and the individual treatment possibilities. For each therapeutic procedure there are specific contraindications which have to be considered. In a prospective comparative study of different established methods of treatment, i.e. hepatic resection, percutaneous ethanol instillation, transcatheter arterial embolisation and tamoxifen therapy, tumor response, survival time, complications and factors, determining prognosis are analysed. The therapeutic concept of the study can thereby be used as a model for the interdisciplinary treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1997

Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years.

In recent retrospective studies, it was shown that subtypes of antimitochondrial antibodies (AMA) can help to discriminate between a benign [only anti-M9 and/or anti-M2 positive by enzyme-linked immunosorbent assay (ELISA)] and a rather progressive course (anti-M2, -M4 and/or -M8 positive). According to different constellations of these AMA subspecificities in ELISA and complement fixation test (CFT), four AMA profiles (A-D) were defined. In 1984 we started a prospective study based on 200 PBC patients with known AMA profiles in order to correlate the antibody pattern with the clinical outcome. Progression was defined primarily as the necessity of liver transplantation and death due to hepatic failure or variceal bleeding. At entry, 18 (9%) of the 200 patients had AMA profile A (only anti-M9), 57 (29%) profile B (only anti-M2 with or without anti-M9), 74 (37%) profile C (anti-M2 in association with anti-M4/-M8 by ELISA), and 51 (26%) profile D (anti-M2/-M4/-M8 by ELISA and CFT). At the beginning of the study, 177 patients had PBC stage I/II. During the observation period of ten years, ten patients died and in 18 orthotopic liver transplantation (OLT) was performed; all these patients belonged to profile C/D. Furthermore, 44% of the patients with profile C and 31% of the patients with profile D progressed to late stages, as defined by histology and clinical manifestations such as portal hypertension and increase of bilirubin, while only one of the patients with profile B and none of the profile A-patients developed late stage PBC. A significant increase of bilirubin was observed only in C/D-patients. AMA profiles did not change during the follow-up. In conclusion, AMA profiles discriminate between a benign and a progressive course of PBC already at early stages.

Adult↗
PubMed1996

[Current diagnosis of chronic nonviral hepatitis].

Apart from viruses, hepatotoxins, hereditary metabolic disorders, immunological factors and cholestasis may cause chronic hepatitis both clinically and histologically. As far as the etiology is concerned, a complete history can be very helpful. The clinical examination, however, is rarely diagnostic. Nevertheless, some clinical signs (e.g. ascites, splenomegaly, spider naevi) are suggestive of cirrhosis. The activities of gammaglutamyl transferase and ALT in the serum are augmented in most of the patients with chronic hepatitis independent of its etiology. Electrophoresis reveals disturbance of serum albumin and globulin ratios. "Basic' laboratory tests are supplemented by carefully selected additional investigations (e.g. immunological tests) according to the history and clinical data of the individual patient. Retrograde cholangiography is diagnostic in the majority of patients suffering from primary-sclerosing cholangitis. Liver histology, best obtained during laparoscopy, allows classification (and prognosis) of the underlying liver disease in many patients. Results of iron and copper determination in liver tissue are diagnostic in cases of congenital liver disease (hemochromatosis, M. Wilson).

Autoimmune Diseases↗
PubMed1996

[Portal hypertension-induced stomach disease].

After esophageal and fundus varices, portal hypertensive gastropathy (PHG) is the second most frequent cause of bleeding in cirrhotic patients. It accounts for 1-8% of primary upper gastrointestinal hemorrhage and 30-60% of secondary acute or chronic bleeding in the first 12 months, mainly after sclerosing therapy of varices. Endoscopy is diagnostic by showing either a typical "mosaic pattern" (mild form) or single or confluent "cherry red spots" (severe form). Helicobacter pylori or NSAID-induced gastropathy are to be distinguished. The therapeutic principles are the same as in drug therapy of esophageal varices. Secondary prophylaxis with propranolol, especially after sclerosing therapy, is recommended, but not primary prophylaxis.

Diagnosis, Differential↗
PubMed1995

[Treatment of chronic virus hepatitis with acetylsalicylic acid].

The treatment of chronic hepatitis B and C with recombinant interferon (IFN) has only poor durable response rates. In the past only the lack of any prior effective therapy regimen could justify the use of this expensive agent. Dose escalating or prolonged treatment courses did not enhance the rate of sustained remissions. Pre- or cotreatment with antiviral (e.g. acyclovir, ribavirin, isoprenosin) or immunomodulating (e.g. prednisone, gamma IFN) drugs have not influenced the resistance to exogenous (IFN) of many patients. The mechanisms underlying resistance to this drug remain unknown. Some hypotheses focus on IFN antibodies, down regulation of IFN receptors or defects in the postreceptor response of cells to IFN. In 1991 Hannigan and Williams (Science 1991; 251: 204-207) described a synergistic signal transduction effect in human fibroblasts after exposure to IFN. Arachidonic acid (AA) activation from membrane phospholipid pools is common to many receptors and can be followed by metabolization of AA by cyclooxygenase to prostanoids, thromboxanes and eicosanoids and by lipoxygenase to leukotrienes; inhibition of these AA oxidation pathways by addition of inhibitors of these enzymes (e.g. indomethacin) resulted in marked amplification of the IFN signal, possibly by using the epoxygenase enzyme family as an alternative pathway. Our data are taken from the pretreatment part of a current study for evaluation of pre- and combination treatment with acetylsalicylic acid (ASA) as cyclooxygenase inhibitor and IFN in chronic hepatitis C. 27 patients with histologically proven chronic active hepatitis C were divided into two groups. Group A (16 patients) were treated with a daily dose of 100 mg ASA orally, and the 11 patients in group B served as untreated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population.

The major histocompatibility complex class II alleles at the HLA-DPB1 locus were investigated in 32 German Caucasoid patients with primary biliary cirrhosis (PBC) and compared with those from 47 normal control patients using molecular genotyping techniques. The second exon of the HLA-DPB1 gene was amplified by polymerase chain reaction (PCR) and hybridized with 25 sequence-specific oligonucleotides (SSOs) to assign the HLA-DPB1 alleles on the basis of known sequence variations, according to the protocols of the Eleventh International Histocompatibility Workshop. A strong association of PBC was found with the allele HLA-DPB1*0301. The allele HLA DPB1*0301 was present in 50% (16 of 32) of the patients with PBC compared with 13% (6 of 47) of normal controls (P corrected < .015), whereas the other HLA-DPB1 alleles showed no significant differences in both groups. The relative risk (RR) estimate for the allele HLA-DPB1*0301 was 6.8 (95% confidence limits: 2.27 to 20.57). In summary, this study clearly demonstrates an association of PBC with the HLA-DPB1*0301 allele in German Caucasoids and may add new data to the immunogenetic background of PBC, suggesting a contribution of the HLA-DPB1 gene to the genetic susceptibility of the disease.

Adult↗
PubMed1994

[Clinical aspects of giant cell hepatitis].

Giant-cell hepatitis in adults is a rare event resembling either chronic non-A, non-B or autoimmune chronic active hepatitis. The etiology is unknown. Paramyxoviruses may be implicated. The clinical picture varies remarkably from mild chronic liver disease to subacute hepatic failure. Liver biopsy is diagnostic, showing giant cells as the common pathological finding. Due to the unknown cause of the disease, treatment is symptomatic. Steroids are applied, as in the case of autoimmune disease, with remarkable results in some patients. In fulminant cases, however, liver transplantation is the only option for cure.

Biopsy↗
PubMed1994

[Hepatitis C: clinical aspects, course and therapy].

Clinically, acute hepatitis C is an asymptomatic disease in up to 90% of cases. Transaminases fluctuate characteristically. Anti-HCV (RIBA-II) and HCV-RNA (PCR) are diagnostic early in the course of the disease. The risk of chronification is high, exceeding 50% of cases, irrespective of disease transmission (parenterally or sporadic). Alpha-interferon is applicated in pilot-studies to reduce the risk of chronification, with varying results. Chronic hepatitis C is an insidious disease. Again, most cases are asymptomatic. Bilirubin is normal. GPT-activity tends to fluctuate during the course. Anti-HCV and HCV-RNA can be detected in serum. About 20% of cases progress to cirrhosis (and HCC) after a long-lasting disease (20 to 30 years after infection). Alpha-Interferon therapy is successful in about 25% of patients.

Acute Disease↗
PubMed1994

[Therapy update 1994].

In carefully selected patients with viral hepatitis B, C (and D?), alpha-interferon (IFN) treatment is associated with a reduction of active viral replication. In chronic hepatitis B, HBeAg clearance rates approximate 40%. About 25% of patients with chronic hepatitis C will profit from a long-lasting (six to twelve months) IFN therapy. Treatment of chronic hepatitis D remains unsatisfactory, since only a minority of patients (less than 10%) finally will clear the virus, even if IFN is administered for one year. Due to the lack of data, IFN therapy cannot be recommended in the moment for patients at special risks, e.g. in the post-transplant situation, during immunosuppressive or hemodialysis therapy.

Chronic Disease↗
PubMed1993

[Clinical significance of cholestatic viral hepatitis].

Modern serologic methods permit the classification of the particular course a virus hepatitis takes into individual types of pathogenesis. This is the case with hepatitis A in which only cholestatic courses have been proved for sure. Cholestatic courses are observed in 5-10% of all cases of acute hepatitis A, with variations from country to country. The duration of the disease is considerably longer than in non-cholestatic hepatitis A. It is between 80 and 130 or even more days! The diagnostic difficulty consists in the clear delimination to other diseases, particularly to intrahepatic cholestasis by drugs or to posthepatic stenosis. Sonography and ERCP are useful technological methods in this situation. Specific therapeutical measures are not available due to the lack of knowledge of the pathogenesis of this type of acute virus infection. The prognosis of cholestatic hepatitis A is good. Short-term glucocorticoid therapy is recommended by some authors in long-term cases, which are associated with pruritus, general weakness, loss of weight and distinct icterus. The course of the disease is obviously not changed by this therapy, but the sometimes agonizing symptomatology is relieved.

Cholestasis, Intrahepatic↗
PubMed1992

[Hepatitis C infection and liver cell carcinoma].

Epidemiological data disclose that the incidence of hepatocellular carcinoma (HCC) is increasing world-wide, whereas the number of cases positive for HBV-marker has remained almost stable, at least in Japan. Data from Europe show positivity of antibodies against hepatitis C virus (anti-HCV) in 72% of HBsAg negative cases with HCC and in 28% of patients positive for HBsAg. Nearly 90% of HBsAg negative patients with HCC showed a histology of cirrhosis or chronic active hepatitis in the noncancerous liver. Almost every third patient had a history of blood transfusion. These results suggest an increasing incidence of HCV - associated HCC's, as it already has been shown for patients suffering from chronic HBV infection.

Antigens, Viral↗