[Current drug treatment of hepatitis C : Useful therapy algorithms taking into consideration economical aspects]. / Aktuelle Arzneimitteltherapie der Hepatitis C : Sinnvolle Therapiealgorithmen unter Berücksichtigung ökonomischer Aspekte.

Treatment of chronic hepatitis C (HCV) has changed dramatically since the approval of the direct-acting antivirals (DAA). Depending on the HCV genotype and the stage of liver disease, sustained HCV clearance can be achieved in more than 95% of patients with a treatment duration of 8-12 weeks in most of the cases. The selection and combination of the drugs depends on previous antivirals therapies, the stage of liver fibrosis, HCV genotype and subtype, viral load at baseline, and renal function. Nowadays, potent antiviral therapy with minimal side effects can be offered to almost every patient. In the real-world setting, a high quality of HCV therapy considering economic aspects has been documented in the German Hepatitis C Registry. A reduction of clinical complications of chronic liver disease by clearance of HCV has already been documented.

Long-lasting tumour response to sorafenib therapy in advanced hepatocellular carcinoma.

The multi-kinase inhibitor sorafenib still remains the only approved agent for advanced HCC. Its benefits typically involve disease stabilisation, whereas an induction of response is rare. We report a series of five cases with extraordinary response to sorafenib. For two patients complete response to sorafenib was reported with a recurrence-free survival of 51 and 21 months. In another HCC patient pretreated with transarterial chemoembolisation (TACE) sorafenib treatment resulted in a complete response with no evidence of disease 18 months after first diagnosis. In patient 4 with unresectable HCC and sorafenib therapy secondary resectability and subsequent liver transplantation was achieved. Patient 5 had stabilised disease for 48 months after TACE and sorafenib treatment. Sorafenib may be very potent in individual patients. Excellent interdisciplinary strategies are required to achieve best results. There is an urgent need of predictive biomarkers to identify HCC patients that will benefit the most.

Colonoscopic allergen provocation test with rBet v 1 in patients with pollen-associated food allergy.

BACKGROUND: After consumption of fruits, nuts, and vegetables, several patients with pollen allergy experience gastrointestinal (GI) tract symptoms that are possibly caused by pollen-associated food allergy. The aim of this study was to evaluate the colonoscopic allergen provocation (COLAP) test using the recombinant birch pollen allergen Bet v 1 (rBet v 1) for in vivo diagnosis of pollen-associated food allergy manifesting in the GI tract. METHODS: Thirty-four patients with a history of adverse reactions to food, GI tract symptoms, and birch pollen pollinosis and five healthy controls underwent COLAP test. Twenty minutes after endoscopic challenge of the cecal mucosa with rBet v 1, the mucosal wheal and flare reaction was registered semiquantitatively, and tissue biopsy specimens were examined for eosinophil mucosal activation. RESULTS: The mucosal reaction to rBet v 1 was correlated with the presence of pollinosis (P = 0.004), history of adverse reaction to Bet v 1-associated food allergens (P = 0.001), and tissue eosinophils' activation (P < 0.001). A wheal and flare reaction in the COLAP test was observed in 13 of 16 patients (81%) with a history of GI tract symptoms associated with the ingestion of Bet v 1-related foods and in four of 18 (22%) patients with a negative history (P < 0.001). The control group did not develop visible mucosal reactions to rBet v 1. Systemic anaphylactic reactions did not occur. CONCLUSIONS: The mucosal administration of rBet v 1 by COLAP test provides a new diagnostic tool that might support the diagnosis of Bet v 1-associated food allergy manifesting in the GI tract.

[Multimodality treatment for hepatocellular carcinoma]. / Multimodale Therapie des hepatozellulären Karzinoms.

Hepatocellular carcinoma represents one of the most important tumor entities worldwide. The great majority of these cases in Germany can be attributed to chronic liver disease (alcohol, viral hepatitis among others), which lead to development of liver cirrhosis and ultimately to hepatocellular carcinoma. While our understanding of the pathophysiological principles underlying the origin of hepatocellular carcinoma has increased considerably in recent years, the prognosis of the majority of these patients remains poor. However, a combined interdisciplinary approach involving internists, surgeons, and radiologists can often achieve effective palliative treatment of the disease. This has recently been reinforced by applying systemic therapies which specifically influence the important biological processes of hepatocellular carcinoma. It can be assumed that by adhering to well-defined treatment algorithms and using improved drug therapy the prognosis of patients with this form of cancer will improve in the future.

Molecular therapy of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of mortality and morbidity. The 5-year survival rate remains less than 5% and in contrast to other solid tumors, survial has changed only little in the last decade. Overall PDAC treatment shows only limited response to conventional chemotherapeutic agents. Several trials on therapy are ongoing and new targeted agents are in development to improve the treatment outcome of this deadly disease. However, our review presents the current developments of molecular therapies, supports the translational PDAC research and encourage you to take part in further clinical studies.

[Sorafenib for the treatment of HCC--the beginning of a new era in the treatment of HCC]. / Die medikamentöse Therapie des HCC mit Sorafenib--der Beginn einer neuen Ara in der Behandlung des HCC.

Sorafenib increases overall survival in patients with advanced HCC by almost three months. However, despite these advances in the treatment of patients with HCC, average overall survival remains below one year. Based on our understanding of hepatocarcinogenesis, the development of new molecular targeting agents and results from biomarker studies in HCC, new therapeutic treatment options are currently being investigated. We summarize recent results on the molecular therapy for HCC and discuss how these can be efficiently tested in patients with HCC.

Molecular therapy for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further.

[Severe drug hepatitis caused by Chelidonium]. / 58-jähriger Patient mit schwerer cholestatischer Hepatitis.

We report the case of a 58-year-old male patient who was admitted with severe acute cholestatic hepatitis. Liver biopsy showed signs of drug-induced hepatitis. Other causes of acute hepatitis were excluded. Therefore, the ingestion of a Chelidonium-containing preparation (celandine) was thought to be responsible for the hepatitis. Shortly after stopping the administration of Chelidonium, the highly pathological levels of several liver parameters began to normalise. As no autoantibodies were detectable, an idiosyncratic reaction as the cause of drug-induced hepatitis is probable. In cases of unknown hepatitis, herbal medications should be taken into account as a possible cause.

Repeated administration of a vitamin preparation containing glycocholic acid in patients with hepatobiliary disease.

BACKGROUND: Until now, hydrophilic and lipophilic vitamin preparations had to be administered separately during total parenteral nutrition. By addition of glycocholic acid, a vitamin supplement (Cernevit, Baxter, Heidelberg, Germany) was developed that combines all vitamins into one vial. However, little information exists about possible consequences of bile acid administration such as glycocholic acid, especially if liver disease is pre-existing. AIM: To evaluate the effects of total parenteral nutrition with a vitamin preparation containing high doses of glycocholic acid in patients with and without liver disease. METHODS: In a prospective, randomized-controlled trial, 74 patients, 36 of them with hepatobiliary disease, received total parenteral nutrition for 16 +/- 11 days, either with Cernevit or control vitamin supplements. Patients were closely monitored for clinical and biochemical parameters including serum bile acid profiles measured by high-performance liquid chromatography. RESULTS: Serum glycocholic acid increased in patients with liver disease treated with Cernevit, whereas total bile acids did not significantly change. Other liver function tests remained stable during treatment. No adverse events during Cernevit administration were noted except for a reversible slight increase of transaminases in one patient. CONCLUSIONS: Cernevit was well tolerated after repeated dosing, even in patients with severe liver disease. Apart from standard controls of liver biochemistry, no specific surveillance is necessary during treatment with Cernevit.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease.

BACKGROUND: Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing. METHODS: A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (>7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio. RESULTS: Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Delta-lactulose/xylose ratio: 0.01+/-0.05 (gln+) vs 0.02+/-0.1 (gln-)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln- group needed surgical intervention. CONCLUSION: Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

Development of an in vitro system for the study of allergens and allergen-specific immunoglobulin E and immunoglobulin G: Fcepsilon receptor I supercross-linking is a possible new mechanism of immunoglobulin G-dependent enhancement of type I allergic reactions.

BACKGROUND: IgE-dependent activation of mast cells (MCs) is a key pathomechanism of type I allergies. In contrast, allergen-specific IgG Abs are thought to attenuate immediate allergic reactions by blocking IgE binding and by cross-linking the inhibitory Fcgamma receptor IIB on MCs. OBJECTIVES: To establish a defined in vitro system using human MCs to study the biological activity of allergens and to investigate the role of allergen-specific IgE and IgG. METHODS: Purified human intestinal MCs sensitized with different forms of specific IgE Abs were triggered by monomeric and oligomeric forms of recombinant Bet v 1, the major birch pollen allergen, in the presence or absence of allergen-specific IgG Abs. Results MCs sensitized with an anti-Bet v 1 IgE mAb or sera obtained from birch pollen allergic patients released histamine and sulphidoleukotrienes after exposure to oligomeric Bet v 1. Monomeric Bet v 1 provoked mediator release only in MCs sensitized with patients sera but not in MCs sensitized with anti-Bet v 1 IgE mAb. Interestingly, MC activation could be induced by supercross-linking of monomeric Bet v 1 bound to monovalent IgE on MCs with a secondary allergen-specific IgG pAb. By using IgG F(ab')2 fragments we provide evidence that this effect is not a result of IgG binding to Fcgamma receptors. CONCLUSION: This assay represents a new tool for the in vitro study of MC activation in response to natural and genetically modified allergens. Fcepsilon receptor I supercross-linking by allergen-specific IgG Abs provides a possible new mechanism of IgG-dependent enhancement of type I allergic reactions.

Malignant peritoneal mesothelioma with mimicry of pseudomyxoma peritonei in a patient with a history of perforated sigmadiverticulitis.

We describe a 57-year-old man who presented with diffuse abdominal pain, abdominal enlargement, vomitus, dyspnea and a weight loss of 30 kg within 6 months. These acute symptoms were preceded by an episode of ascites and an acute sigmadiverticulitis 7 months ago. Ultrasonography and computed tomography were suggestive of pseudomyxoma peritonei. However, malignant mesothelioma peritonei was diagnosed by open surgery with biopsy for histological examination. Despite R-2-resection of the tumor and following open hyperthermic intraperitoneal chemotherapy with initial remarkable recovery the patient died 5 months after therapeutical intervention. Malignant peritoneal mesothelioma is an extremely rare tumor with great diagnostic and therapeutic difficulties. We report a case including diagnostical work up and the medical surgical therapy of this disease.