Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.

Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin. Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly) for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24-week drug-free period. Virologic response rates did not differ between the two doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose group (P = ns). The corresponding values in patients infected with HCV genotype 2 or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24 weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the treatment without relevant dose reduction or premature termination. In combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis.

[Iron-deficiency anemia and gastrointestinal bleeding]. / Eisenmangelanamie bei gastrointestinalen Blutungen.

The physiology of iron homeostasis, clinical presentation, diagnosis, differential diagnosis and therapeutic options in iron-deficiency anemia are discussed. Iron deficiency is the most common haematological disorder encountered in general practice and iron-deficiency anemia is the most frequently occurring anemia throughout the world. Blood loss is a major cause of iron-deficiency anemia. Gastrointestinal bleeding is the most common cause of iron deficiency in adult men and is second only to menstrual blood loss as a cause in women. Iron-deficiency anemia is not a disease itself but a manifestation of an underlying disease, searching for the latter is therefore crucial and may be of far greater importance to the ultimate well-being of the patient than repleting iron stores. The symptoms and signs of iron deficiency are partially explained by the presence of anemia. However, there also appears to be a direct effect of iron deficiency on the central nervous system. The most important screening investigations for iron deficiency in clinical practice are the haemoglobin, the haematocrit and the mean corpuscular volume (MCV). The single most important measure of iron status is the serum ferritin, values below the lower limit of normal being specific for iron deficiency. In inflammation, hepatopathy and haemolysis serum ferritin is also released leading to falsely elevated values, therefore an analysis of the C-reactive protein (CRP) should always accompany the analysis of serum ferritin. Repleting iron stores is usually done with oral iron therapy, the available preparations are comparable with respect to efficacy, side effects and costs. The main indications for parenteral iron therapy are intolerance to oral iron, intestinal malabsorption and poor compliance to an oral regimen. The iron sucrose preparation should bepreferentially used for that purpose, the total dose is calculated from the amount of iron needed to restore the haemoglobin deficit plus an additional amount to replenish iron stores.

[Pitfalls in the workup of common hepatobiliary problems]. / Fallgruben in der alltäglichen hepatobiliären Diagnostik.

Hepatobiliary problems are not uncommon in general practice. Many cases can be solved on the basis of a thorough history, clinical examination, blood tests and abdominal ultrasound. The focus of this tutorial paper lies on a number of possible pitfalls in the workup of such problems, based on brief case histories. Atypical presentations of lithogenic biliary obstruction, with or without cholangitis, are discussed as a relatively frequent cause of management difficulties. Furthermore, certain caveats in the interpretation of tumor marker CA19-9, prothrombin time/INR, and ferritin are highlighted.

[Endoscopic palliation of gastrointestinal tumor symptoms--what the GP should know]. / Endoskopische Palliation von gastrointestinalen Tumor-Symptomen--Wissenswertes für den Praktiker.

Gastrointestinal endoscopy offers a variety of methods for palliative treatment of tumor symptoms, most importantly self-expanding metal stents. Stent insertion achieves effective recanalisation of malignant stenoses in various locations of the gastrointestinal tract. This tutorial paper briefly reviews some of these methods. Special consideration is given to a number of practical points regarding patient follow-up by the general practitioner.

[Rational assessment and therapy of diarrhea]. / Rationelle Abklärung und Therapie der Diarrhoe.

Patient history, physical examination and basic laboratory tests often allow the clinician to suspect one of the numerous aetiologies of diarrhea and consequently establish a rapid diagnosis. Otherwise, the workup of diarrhea, especially when chronic, may represent a challenge. In this brief tutorial article a practical algorithm is proposed to guide the clinician through the initial diagnostic steps as well as therapeutic trials.

[New therapeutic possibilities in chronic hepatitis C]. / Neue Therapiemöglichkeiten bei der chronischen Hepatitis C.

This article briefly reviews the results of antiviral treatment of chronic hepatitis C with interferon-alpha. Its relation to the natural course of the illness is discussed. Interferon monotherapy achieves definitive viral elimination in a small minority of patients only. The therapeutic response rate can be enhanced by combining interferon-alpha with ribavirin as well as by increasing interferon dosage or prolonging treatment. A number of questions remain unanswered with regard to the optimal treatment modality and cost-effectiveness. Thus the current recommendation is to treat suitable patients within the frame of controlled studies.

[Endoscopic palliation in esophageal carcinoma]. / Endoskopische Palliation des Osophaguskarzinoms.

Oesophageal carcinoma is frequently diagnosed at an advanced stage of the disease not amenable to curative treatment. For these patients relief of dysphagia is of foremost importance to quality of life for the remaining survival time. There is a wide choice of palliative therapeutic methods. The majority of patients will benefit from implantation of a self-expanding metal stent. In this article the most frequently employed techniques of endoscopic palliation are briefly reviewed, with emphasis on metal stents.

[Gastric carcinoid--pathogenesis and treatment]. / Das Magenkarzinoid--Pathogenese und Therapie.

Gastric carcinoid tumours are rare neoplasms of neuroendocrine origin. They are believed to grow from enterochrommaffin-like (ECL) cells. Three different types of tumours can be distinguished: type I: hypergastrinaemic, induced by achlorhydria in chronic atrophic gastritis; type II: hypergastrinaemic, associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia syndrome type 1; type III: sporadic. The trophic effect of gastrin on ECL cells is of crucial importance in the pathogenesis and treatment of hypergastrinaemic carcinoids. In these patients, hypergastrinaemia leads to ECL-hyperplasia, -dysplasia and -neoplasia. Hypergastrinaemic carcinoids often follow a very benign course, which makes it possible to avoid surgery, at least in patients at high surgical risk. The management of these three types is discussed.