Therapie der autoimmunen Lebererkrankungen

Since the 1950s, autoimmune hepatitis has been recognized as a chronic liver disease that responds to treatment with steroids. Nevertheless, even today 25% of all diagnosed patients still present with liver cirrhosis, which emphasizes the importance of a timely and efficient diagnosis. Steroid-containing immunosuppression is characterized by a high rate of unwanted side effects. For non-cirrhotic patients, the synthetic steroid budesonide, which is characterized by high first-pass metabolism, represents a study-evaluated alternative. In the new guidelines for the management of primary sclerosing cholangitis, the therapeutic role of ursodeoxycholic acid has been modified, with no other effective alternative drugs being available. Management of sclerosing cholangitis is also made more difficult by the high risk of cholangiocarcinoma and colon carcinoma in addition to new differential diagnoses such as secondary sclerosing cholangitis and IgG4-associated cholangitis. IgG4-associated cholangitis can mimic primary sclerosing cholangitis but--in contrast-- can respond to the administration of steroid-containing immunosuppression.     

Autoimmune Lebererkrankungen

Ohne Zusammenfassung

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Lebererkrankungen in der Schwangerschaft

In pregnancy physiologically induced altered levels in liver function tests have to be distinguished from liver diseases. These can be divided into clearly pregnancy-associated and liver diseases coincidentally occurring with pregnancy, such as gall-stones, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson??s disease, hepatitis B and C infections and cirrhosis of the liver. Pregnancy-associated liver diseases include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, preeclampsia/eclampsia, the hemolysis, elevated liver tests and low platelets (HELLP) syndrome and acute fatty liver of pregnancy. A close collaboration between obstetricians and hepatologists is recommended. In terms of pregnancy-related entities this often means prompt delivery of the neonate, whereas in pregnancy-independent liver diseases best supportive care including supervision of the embryo/fetus has priority.     

Lebertransplantationen bei autoimmunen Lebererkrankungen

Cirrhosis due to autoimmune liver disease is an indication for liver transplantation. In Eurotransplant countries, the model for end-stage liver disease (MELD) score was introduced in December 2006. The lab-MELD is based on creatinine, bilirubin, and prothrombin time expressed as the international normalized ratio (INR). If patients with primary sclerosing cholangitis develop complications, such as biliary sepsis, standard exceptional criteria (match-MELD) might be added to increase the priority of organ allocation. Because of excellent short-term outcomes after liver transplantation, attention has shifted to improving long-term survival and particularly to treating recurrent disease. Diagnosis of disease relapse in autoimmune and cholestatic liver disease is more challenging than in the non-transplant setting. However, despite limited therapeutic options for recurrent autoimmune liver disease after transplantation, affected patients exhibit excellent long-term survival.     

Seltenere hereditäre Lebererkrankungen

Besides the primary form of hemochromatosis and Wilson’s disease, there are many other hereditary liver diseases. All of these are hereditary syndromes of either unconjugated or conjugated hyperbilirubinemias; cholestatic diseases, such as alpha-1 antitrypsin deficiency and Alagille syndrome; or many different metabolic diseases, including galactosemia and porphyrias. Clinically, one can see a spectrum of diseases, from those with medical irrelevance up to neonatal terminal liver insufficiency. Therefore, the therapeutic spectrum ranges from no indication for treatment, to pharmaceuticals, to (early) liver transplantation.     

Molekulare Diagnostik bei genetischen Lebererkrankungen

New insights into the genetic basis of diseases are being generated at an ever increasing rate. This review discusses the application of molecular genetics with a special focus on hereditary diseases of the liver. The application of molecular genetics in everyday clinical routine is hampered by the sometimes difficult interpretation of test results. These difficulties include the prediction of disease penetrance (e.g. in patients with a homozygous HFE C282Y mutation), the presence of multiple mutations of a particular gene (e.g. in Wilson??s disease), the presence of mutations with varying functional consequences (e.g. in genes responsible for recurrent cholestasis syndromes) and the importance of exogenous factors modulating disease expression. To date the most significant impact of genetics has been to increase our understanding of disease etiology and pathogenesis and to reliably identify siblings of affected patients with a risk to develop symptomatic disease.     

Lebererkrankungen bei Reiserückkehrern

Die Gastroenterologie - Aufgrund der ungebrochenen Reisefreudigkeit spielen reisespezifische Erkrankungen in Deutschland weiterhin eine große Rolle. Oft ist die Leber dabei primär oder...     

Lebererkrankungen bei Diabetes mellitus – Fallberichte

Die Diabetologie - Lebererkrankungen gehören seit Jahrzehnten zum Alltag von Allgemeinmedizinern und Internisten, sie sind bei Diabetes mellitus häufig, werden aber oft wenig beachtet....     

Gentherapie von hereditären Lebererkrankungen

Gene therapy has been explored for the treatment of hereditary monogenic liver diseases. It includes gene repair, gene replacement as well as hepatocyte, stem cell or liver transplantation. These strategies have been successfully explored in preclinical in vivo models of hereditary monogenic liver diseases as well as in individual patients. While their principle and efficacy has been demonstrated, in principle, numerous problems need to be solved before gene therapy will complement or replace existing therapeutic options. Furthermore, recent developments in the field of stem cell biology with the generation of individual stem cells from skin fibroblasts will certainly also have an impact on further developments in gene therapy in general and stem cell transplantation in particular.     

Allgemeine Therapie

Ohne Zusammenfassung     

Allgemeine Therapie

Ohne Zusammenfassung     

Allgemeine Therapie

Ohne Zusammenfassung     

Antibradykarde Therapie

Pacemaker therapy (PMT) in grown-up congenital heart disease (GUCH) must meet the demands of a young, dynamic and heterogeneous group of patients. The duration of the therapy has to be planned for several decades and should be accompanied by an invasive procedure at the very least. Most of the patients enter adulthood with their pacemaker (PM) already implanted; for others the indications can be derived from the published guidelines for GUCH and PMT, but need to be adjusted to the individual situation of the patient. Depending on the underlying heart disease the decision on the use of either an epimyocardial or a transvenous PM system has to be made. Both electrodes and PM should correspond to the latest technical developments to optimally adapt to the patients’ multiple requirements. In the case of PM system revisions abandoned leads should be removed and vascular stenosis or occlusions cleared to be prepared for later revisions. During any cardiac surgery epimyocardial PM systems should be checked against the patient’s needs and expanded or revised accordingly. Epimyocardial resynchronization systems in particular offer more opportunities for compensating for cardiac dysfunction with greater reliability using a second ventricular lead. The PMT is an essential part of the medical treatment for many patients with GUCH and contributes significantly to the well-being and quality of life. Against this background, a competent and consequent follow-up regime requires experienced physicians. An integrated telemetric monitoring system for the PM has proven valuable and supports the early recognition of cardiac arrhythmia.     

Antithrombotische Therapie

Platelet function is one of the main components in the development of atherosclerosis and atherothrombotic clinical events. Patients with diabetes mellitus in particular exhibit increased platelet activity and reduced inhibition in response to platelet inhibitors. The general administration of aspirin in all patients with diabetes mellitus type 2 is recommended by some scientific societies. In clinically stable patients, secondary prevention with clopidogrel is superior to the use of aspirin. In patients with diabetes mellitus, the relative risk reduction with clopidogrel is four times higher than the risk reduction in non-diabetics. Dual platelet inhibitor therapy has no clinical advantages in these stable patients. In contrast, dual antiplatelet therapy is significantly superior to monotherapy with aspirin in patients with acute coronary syndrome. Although the relative risk reduction in patients with diabetes mellitus is comparable to the rate in non-diabetics, the absolute number of events prevented in these patients is significantly higher due to the higher event rate. The results presented suggest that the clinical outcome in patients with diabetes mellitus is mainly determined by the degree of platelet activation and its effective inhibition by platelet inhibitors.