Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPSS) in 40 patients with hepatocellular carcinoma.

BACKGROUND: Portal hypertension and hepatocellular carcinoma (HCC) are major complications of advanced liver cirrhosis. Thus, patients are often affected by both complications. Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective treatment for portal hypertension and its complications. However, no established guidelines for the treatment of symptomatic portal hypertension in HCC patients are currently available. In addition, only limited information exists about the consequence of TIPSS implantation in patients with HCC. AIM: To evaluate the efficacy, safety and overall survival in HCC patients who underwent TIPSS implantation. METHODS: Forty HCC patients with portal hypertension who were treated with TIPSS between 1995 and 2012 were included in the analysis. Medical records and imaging studies were analysed. The indication for TIPSS implantation, procedure-related complications, treatment success and overall survival were assessed. RESULTS: TIPSS implantation was performed in 23 patients (57.5%) due to treatment refractory ascites, in 14 patients (35.0%) due to recurrent variceal bleeding and in three patients (7.5%) due to ascites and variceal bleeding. Primary technical success was assessed in all patients. After TIPSS implantation, no variceal bleeding reoccurred and ascites was controlled in 74.1%. No severe procedure-related complications and no deterioration of liver function were observed. Post-TIPSS hepatic encephalopathy occurred in 40.0% of all patients. 30-day, 90-day-, 1-year- and 5-year survival rates were 97.5%, 75.0%, 42.5% and 7.5%, respectively. Median overall survival after TIPSS implantation was 180 days. CONCLUSION: Transjugular intrahepatic portosystemic shunt implantation is an effective and safe treatment for portal hypertension in patients with HCC.

[Hepatocellular carcinoma - from immunobiology to immunotherapy]. / Das hepatozelluläre Karzinom - von der Immunbiologie zur Immuntherapie.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide with an increasing incidence. The clinical outcome is influenced by the underlying liver cirrhosis, the size of the tumour at the time of diagnosis and the few therapeutic options currently available. In recent years there has been a lot of progress in the understanding of HCC immunobiology. This review summarizes our current knowledge of HCC biology, the role of chronic inflammation in carcinogenesis and the role of tumour-specific immune responses. Furthermore, we will present potentially new, immune-based therapies that might open up new avenues for the treatment of HCC.

[A rare cause of an indistinct liver lesion in an elderly woman]. / Seltene Ursache einer unklaren Leberläsion bei einer 76-jährigen Patientin.

HISTORY: A 76-year-old woman was admitted with a two-months history of pain in the right upper abdomen and nausea. There was no disease or premedication in her history. INVESTIGATIONS: Labaratory tests revealed a normocytic anemia, elevated liver enzymes and signs of cholestasis. An MR of the abdomen showed a hyperperfused tumor in the liver segments IV, V and VIII, likely to be a hepatocellular carcinoma. However, tumor markers including AFP were not elevated. A liver biopsy revealed the final diagnosis of angiosarcoma. THERAPY AND COURSE: Because the tumor was not resectable transarterial chemoembolisation (TACE) with doxorubicin was performed with palliative intent. Six weeks later a CT scan revealed extensive tumor progression. Therefore no further causal tretament was performed. With best supportive care the patient died within 4 weeks after she had been discharged. Occupational history revealed that the woman had been exposed to polyvinylchloride for six years when she had worked in a factory producing varnish aerosol cans 44 years ago. CONCLUSION: Angiosarcomas of the liver are rare, highly malignant and diffuse infiltrating vascular tumors with rapid growth and poor prognosis. In patients who have been exposed to polyvinylchloride and present with an indistinct lesion of the liver an angiosarcoma should be considered.

[The hepatocellular carcinoma: alternative therapeutical strategies]. / Das hepatozelluläre Karzinom: alternative Therapiestrategien.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Therefore, the development and evaluation of novel HCC treatment strategies such as the use of antiangiogenic, antiproliferative or antiinflammatoric drugs, immune therapeuticals, gene therapy and internal or external radiation are of utmost importance. This review should give an overview of possible alternative therapies in HCC treatment.

[Regional therapy of liver tumors]. / Regionale Therapie von Lebertumoren.

Malignant liver tumors are either originating from the liver, such as the primary liver tumors hepatocellular carcinoma and the cholangiocellular carcinoma, or metastases from extrahepatic malignancies. Apart from surgical procedures (resection, liver transplantation) percutaneous local-ablative (ethanol injection, radiofrequency thermal ablation as well as radiation therapy) and transarterial interventions are non-surgical therapeutic options. While these regional therapies have been shown in randomised controlled studies to be effective for hepatocellular carcinoma, their therapeutic efficacy in cholangiocellular carcinoma and liver metastases has not been shown. In the following we will summarize the regional therapeutic options in primary and secondary liver tumors.

Serum markers of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with increasing incidence worldwide. Most of patients with HCC are diagnosed at a late stage. Therefore, the prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. Screening strategies including alpha-fetoprotein (AFP) and ultrasound every 6 months in patients with liver cirrhosis, the major risk factor for HCC development, have been recommended to detect HCC at earlier stages amenable to effective treatment strategies. AFP, however, is a marker with poor sensitivity and specificity and the ultrasound is highly dependent on the operator's experience. Apart from AFP, lens culinaris agglutinin-reactive AFP and des-gamma carboxyprothrombin and several other biomarkers (e.g., glypican-3, human hepatocyte growth factor, and insulin-like growth factor) have been proposed as markers for HCC detection. In addition, with recently employed techniques, such as gene-expressing microarrays and proteomics, it is to be expected that new HCC-specific markers will become available in the near future. For all such proposed markers, however, the clinical usefulness has to be carefully evaluated and validated.

[Vasculitis and liver disease]. / Vaskulitiden bei Lebererkrankungen.

Extrahepatic manifestations of liver diseases especially the hepatitis B virus (HBV)-infection and hepatitis C virus (HCV)-infection may occur during acute and/or chronic viral hepatitis. Besides a serum like illness with fever, arthralgia and urticaria, haematological disorders with transient bone marrow suppression and cryoglobulinemia have been described. Vasculitis is a rare complication of viral hepatitis. However, HCV can trigger a cryoglobulinemic vasculitis and may clinically present with purpura, arthritis, neuropathy, glomerulonephritis and fatigue. Panarteritis nodosa is frequently associated with HBV infection, which is caused by deposits of immune complexes in the arterial wall. Therapy of both types of vasculitis depends on the severity of disease and may include immunosuppressive agents as well as antivirals.

[Hereditary liver diseases]. / Hereditäre Lebererkrankungen.

In recent years the identification and characterization of gene defects underlying hereditary liver diseases lead to a better understanding of their pathogenesis. Heditary hemochromatosis, Wilson's disease and alpha1-antitrypsin deficiency are the most common hereditary liver diseases. While gene defects and disease manifestation may correlate, genetic testing is generally not contributing to diagnosis. This review summarizes the clinical manifestations, diagnosis and therapy of the most frequent hereditary liver diseases: hereditary hemochromatosis, Wilson's disease and alpha1-antitrypsin deficiency.

[Suppressor T-cells: immunologic regulator cells and clinical perspectives]. / Suppressor-T-Zellen: Immunologische Regulatorzellen mit klinischer Perspektive.

Regulatory T cells modulate immune responses in different clinical settings. Here, we summarize the role of CD4(+)CD25(+) regulatory T cells in autoimmunity, transplantation, infectious diseases and tumor immunity.

[Best supportive care of hepatocellular carcinoma]. / Hepatozelluläres Karzinom.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The major etiologic risk factors include toxins (alcohol, aflatoxin B(1)), hepatitis B and C virus infection as well as various inherited metabolic disorders. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. The diagnosis is based on biochemical and imaging tests as well as histology. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Radio- or chemotherapy are mostly ineffective. Therefore, the development and evaluation of novel HCC treatment strategies as well as the implementation of existing and the development of new measures to prevent HCC are of utmost importance. The better understanding of the clinical and molecular pathogenesis of HCC should lead to improved diagnostic, therapeutic and preventive strategies with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.

[The role of the virus specific T-cell response in acute and chronic HBV and HCV infection]. / Die Rolle der virusspezifischen T-Zellantwort bei der akuten und chronischen Hepatitis-B- und -C-Virusinfektion.

Infections with hepatitis B (HBV) and hepatitis C virus (HCV) are worldwide one of the most frequent causes for chronic liver disease, liver cirrhosis and hepatocellular carcinoma. The mechanisms responsible for the elimination or the persistence of the virus are not well understood. The immunopathogenesis of HBV and HCV infection is primarily mediated by virus specific CD4+- and CD8+-T-cells. During acute infection a strong and multispecific T-cell response against different viral epitopes can be detected and is associated with the clearance of the virus. In case of viral persistence virus specific T-cells contribute to liver inflammation. In this article we summarize the current concepts about the role of the virus specific T-cell response in acute and chronic HBV and HCV infection.