Hypercalcemia in a patient with cholangiocarcinoma: a case report

<p>Abstract</p> <p>Background</p> <p>Humoral hypercalcemia of malignancy is rarely associated with cholangiocarcinoma (CC).</p> <p>Case report</p> <p>A 77-year-old man was admitted with confusion. Computer tomography showed a large multinodular mass in the right lobe of the liver and smaller lesions in the right lung. Liver histology confirmed the diagnosis of CC. Elevated calcium levels and suppressed intact parathyroid hormone in the absence of skeletal metastases or parathyroid gland pathology suggested the diagnosis of humoral hypercalcemia of malignancy (HHM). Treatment of hypercalcemia with saline infusion, loop diuretics, biphosphonate and calcitonin was effective in normalizing calcium levels and consciousness state within 48 hours, but a relapse occurred 4 weeks later and the patient succumbed to his disease.</p> <p>Conclusion</p> <p>Clinicians should be aware of this rare manifestation of CC as prompt and aggressive correction of hypercalcemia alleviates symptoms and improves patient's quality of life, despite the poor overall prognosis.</p

Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatitis-associated aplastic anemia is a common syndrome in patients with bone marrow failure. However, hepatitis-associated aplastic anemia is an immune-mediated disease that does not appear to be caused by any of the known hepatitis viruses including hepatitis C virus. In addition, to the best of our knowledge there are no reported cases of patients with chronic hepatitis C virus infection developing aplastic anemia associated with pegylated interferon alpha 2a treatment.</p> <p>Case presentation</p> <p>We report the case of a 46-year-old Greek man who developed severe aplastic anemia during treatment with pegylated interferon alpha 2a for chronic hepatitis C virus infection. He presented with generalized purpura and bruising, as well as pallor of the skin and mucous membranes. His blood tests showed pancytopenia. He underwent allogeneic bone marrow transplantation after completing two courses of immunosuppressive therapy with antithymocyte globulin and cyclosporin A.</p> <p>Conclusions</p> <p>The combination of a specific environmental precipitant represented by the hepatitis C virus infection, an altered metabolic detoxification pathway due to treatment with pegylated interferon alpha 2a and a facilitating genetic background such as polymorphism in metabolic detoxification pathways and specific human leukocyte antigen genes possibly conspired synergistically in the development of aplastic anemia in this patient. Our case clearly shows that the causative role of pegylated interferon alpha 2a in the development of aplastic anemia must not be ignored.</p

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma&mdash;A Single-Center Study

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged &gt; 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated

Decreased serum DNase1-activity in patients with autoimmune liver diseases

<p>Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (<i>p</i> < 0.02, <i>p</i> < 0.001, <i>p</i> = 0.03), NAFLD/NASH (<i>p</i> < 0.001) and healthy (<i>p</i> < 0.001). No significant difference was found in between each specific ALD. In AIH, DNAse1-activity was positively correlated with aspartate aminotransferase (AST) (<i>p</i> < 0.02), bilirubin (<i>p</i> < 0.01) and increased IgG (>1400 mg/dl; <i>p</i> < 0.05); in PBC, with AST (<i>p</i> < 0.01), alanine aminotransferase (ALT) (<i>p</i> < 0.03) and anti-mitochondrial antibodies (AMA) (<i>p</i> = 0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (<i>p</i> < 0.05). In AIH, complete responders were characterized by increased baseline DNase1-activity compared to partial responders, relapsers and non-responders (<i>p</i> < 0.02), whereas it was significantly increased after achievement of remission (<i>p</i> < 0.001). Serum DNase1-activity is significantly decreased in ALD patients, indicating its potential implication in their pathogenesis. Furthermore, DNase1-activity could be used as a new surrogate biomarker for predicting response to AIH treatment.</p