Antonios Moulakakis

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.

Objective Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. Methods Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Students t-test, P < 0.05). Results Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6–120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). Conclusions Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease

Objective To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. Methods One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Students t-test and the non-parametric Kruskall–Wallis test (P<0.05). Results Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80±16.80 ng/ml) than in those without bacterial infection (0.21±0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. Conclusion Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.

Case report: mixed cholestatic/hepatocellular liver injury induced by the herbicide quizalofop-p-ethyl.

Context Quizalofop-p-ethyl is an often applied, slightly toxic herbicide for which no severe toxicity has been reported in humans. Case presentation We present the case of a farmer exposed to quizalofop-p-ethyl who presented with obstructive cholestasis. A complete workup disclosed no other cause of liver pathology, but liver biopsy established drug-induced hepatotoxicity. The patient was treated with ursodeoxycholic acid and prednisolone, and was recovered fully 70 days after his exposure to the herbicide. The patient was followed for the next 9 months. Conclusion Quizalofop-p-ethyl can induce a mixed cholestatic/hepatocellular liver injury. We discuss possible mechanisms implicated in liver injury after exposure to quizalofop-p-ethyl. Relevance to clinical or professional practice In patients presenting with mixed cholestatic/ hepatocellular liver injury, occupational exposure to quizalofop-p-ethyl in the course of agricultural use should be investigated.

Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin

BACKGROUND The aim of this study was to investigate the effect of patients age on the impact of typically proposed predictors of sustained virological response (SVR) in treatment-naïve, high-pretreatment viral load (>700.000 IU/ml), chronic hepatitis C (CHC) patients treated under real-life conditions in Greece. METHODS We retrospectively analyzed 185 CHC patients (14.4% cirrhotics) who had been treated with weight-adjusted dosing (1.5 microg/kg per week) of pegylated interferon-a2b (PEG) plus genotype-based ribavirin (RIB) for 24 or 48 weeks of treatment, based on viral genotype. SVR was confirmed by undetectable serum HCV-RNA 6 months after the end of treatment. RESULTS Overall, 68.5% of patients exhibited SVR and 31.5% were non-responders (non-SVRs). Among the non-SVRs, 71.4% were infected with HCV genotype-1. Importantly, 71.4% of genotype 4-infected treated patients exhibited SVR. In the multivariate analyses, only the early histological stage of liver disease (p=0.015) and the presence of genotype non-1 infection (p=0.003) were independent predictors of SVR. For patients younger than 35 years, none of the baseline parameters and neither viral genotype (p=0.284) nor the stage of liver disease (p=0.351) was an independent predictor of non-SVR, whereas for patients between 35 and 55, only the presence of genotype-1 infection independently predicted non-SVR (p=0.008). For older patients (>55 years), only the histological stage of liver disease (p=0.047) and not the viral genotype (p=0.275) independently predicted non-SVR. CONCLUSIONS The impact of the typical predictors of SVR, such as viral genotype and liver histopathology, is modified according to patients age in currently approved combination treatment.

Unusual onset of varicella zoster reactivation with meningoencephalitis, followed by rhabdomyolysis and renal failure in a young, immunocompetent patient

We present an unusual onset of meningoencephalitis due to VZV reactivation, with increased intrathecal production of IgG VZV antibodies and negative PCR, in a young, immunocompetent adult. Herpes zoster erupted 5 d later. Rare complication of VZV-related rhabdomyolysis occurred, with subsequent ARF, in combination with acyclovir and ceftriaxone. The patient recovered fully and remained healthy.

Possible green tea-induced thrombotic thrombocytopenic purpura

PURPOSE A case of a patient who developed thrombotic thrombocytopenic purpura (TTP) after consuming a weight-loss product containing green tea is reported. SUMMARY A 38-year-old, 68-kg Caucasian woman arrived at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. She had no symptoms of infection and denied illegal drug use. Her medical history included hypothyroidism, for which she was treated with levothyroxine 150 microg daily for the past four years. She reported that she had been using a green tea preparation for the two months before admission to lose body weight. The daily preparation contained 200 mg of green tea extract 5:1, equivalent to 1 g of natural green tea. On clinical examination, the patient appeared acutely ill and was afebrile, with pallor, petechiae, and purpura of the extremities. Laboratory test results at the time of admission revealed that the patient had anemia and marked thrombocytopenia. A peripheral blood smear demonstrated a feature of microangiopathic hemolytic anemia. Immunoglobulin G autoantibodies against ADAM metallopeptidase with thrombospondin type 1 motif, 13 were detected. On hospital day 3, the patient appeared confused and exhibited aphasia that was initially transient but then recurrent. Brain computerized tomography did not exhibit focal pathology. Over the next few days, her neurologic symptoms subsided and her platelet count and hematocrit value gradually increased. Plasmapheresis was performed (12 procedures). Corticosteroid treatment was also initiated. After 20 days of hospitalization, the patient was discharged. CONCLUSION A 38-year-old woman developed TTP after consuming a weight-loss product containing green tea extract for two months.

Atypical autoimmune polyglandular syndrome type 3 overlapped by chronic HCV infection resulting in carcinogenesis and fatal infection.

The case of a woman with insulin-dependent diabetes mellitus, autoimmune thyroiditis, atrophic gastritis, pernicious anemia, and immunologic thrombocytopenic purpura consisting of autoimmune polyglandular syndrome type 3 associated with a history of gonadal failure is reported. Hepatitis C viral infection added xerophthalmia, lymphocytic sialadenitis, and exacerbation of idiopathic thrombocytopenic purpura. This unique disease constellation was complicated with splenic marginal zone lymphoma and gastric carcinoids. A lung infection, initially treated on an outpatient basis, proved fatal to the patient.

Diabetes mellitus responsive to corticosteroids in autoimmune pancreatitis.

To the Editor: Autoimmune pancreatitis (AIP) is a recently described entity characterized by a diffuse swelling of the pancreas, with lymphocyte infiltration, hypergammaglobulinemia, and onset of diabetes mellitus. Antibodies against carbonic anhydrase II (ACA II) and lactoferrin are frequently found, and high levels of IgG 4 are prominent in the majority of the patients. We observed a 42-year-oldman, immigrant fromPakistanworking inGreece, who was treated successfully with interferon a-2b (IFN-a) because of chronic hepatitis C. HCV-RNAwith PCR, 3 years after the end of the treatment, is negative. He was not diabetic and his blood proteins were within normal limits. Eighteen months after the end of the treatment with IFN-a, he complained about abdominal pain, polyuria, andpolydipsia. Sixmonths later, the patient came for consultation, and we found that he was diabetic. Fasting plasma glucose was 325 mg/dL and HbA1c was 8% (normal range<6%). He was treated with insulin with satisfactory regulation. Serum total protein was 9 g/dL, albumin 4.5 g/dL, and globulin 5 g/dL (c = 24.6%). IgG subtypes were as follows: IgG1 = 1430 mg/dL (normal range 490–1140 mg/dL), IgG2 = 484 mg/dL (normal range 150–460 mg/dL), IgG 3 = 83 mg/dL (normal range 20–110 mg/dL), and IgG4 = 136 mg/dL (normal range 8–140 mg/dL). Antibodies against the pancreatic islets, antinuclear, antimitochondrial, antismoothmusclewere negative. ACA II and lactoferrin are not available in Greece. Ultrasound examination of the abdomen revealed sausage-like swelling of the pancreas. Magnetic resonance cholangiopancreatography revealed no abnormality in the pancreatic duct and the biliary system. Because AIP was strongly suggested, the patient was treated with prednisolone (40 mg/day) with tapering the dose for a period of 2 months. The blood sugar was regulated with insulin. By that treatment, abdominal pain was relieved and there was reduction of the size of pancreas to normal. Also, the levels of globulins came to normal. The necessary units of insulin were low, so the patient was put on tablets of gliclazide and pioglitazone. The fasting blood sugar now is about 130 mg/dL. AIP is of unknown origin entity, and only few cases have been reported in the literature. It has been referred to as sclerosing pancreatitis, chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct, and sclerosing pancreatocholangitis. ACA II and lactoferrin antibodies are usually found, but these are not specific since both have been detected in other autoimmune diseases. Also, IgG 4 levels are elevated but not to all patients, as in our case. The disease is characterized by CD8 and CD4 T lymphocytes infiltration that surrounds ductal cells, which express HLA class II molecules. These lymphocytes secrete cytokines that can suppress and destroy b cells of the pancreas and that could be the explanation of the early appearance of diabetes mellitus. Corticosteroids may suppress the release of cytokines, permitting islet regeneration and eventually the partial restoration of insulin secretion. As for the etiology of AIP in this case, IFN-a-induced autoimmunity could be the trigger factor, despite the long period between the stop of the treatment with IFN-a and the onset of AIP.

Paraneoplastic cerebellar degeneration: initial presentation in a patient with anaplastic T-cell lymphoma, associated with ichthyosiform cutaneous lesions.

Paraneoplastic neurological disorders (PND) are defined as syndromes that represent remote effects of malignancy at the nervous system that are not caused by direct or metastatic infiltration [1]. The mechanism is believed to be an autoimmune response to nerve cells’ antigens that are also expressed by the tumor [2]. Several types of neuronal autoantibodies have been detected in the serum of many, though not all, patients with PND [3]. Paraneoplastic cerebellar degeneration (PCD) is a classical PND. Typically, it is a symmetric pancerebellar syndrome that starts with unsteady gait and usually progresses within few weeks to severe disability that renders the patient bed bound, dysarthric, and trembling [3]. PCD has been associated with lung and gynecological cancers, and Hodgkin lymphoma [4]. We report a young man with PCD as the initial presentation of anaplastic T-cell lymphoma, followed by the eruption of ichthyosiform skin lesions. A previously healthy 28-year-old man presented dysarthria without any other complaints. In the next few days, the dysarthria worsened, and he also developed gait impairment and dysphagia. At that time, due to misdiagnosis, the patient was consecutively hospitalized in an internal medicine and then in a psychiatric department. Eventually, three weeks after the disease onset, he was transferred to the neurological department in stupor. The physical examination revealed an afebrile patient, with vertical nystagmus, dysarthria, and dysphagia. He could not walk or stand and he could only follow simple commands because of ataxia. He had normal muscular strength, brainstem reflexes and deep tendon reflexes, but increased tone of all limbs and diffuse hyperkinetic movements including myoclonus and chorea. He underwent an extended diagnostic work up that revealed no evidence of a metabolic cause of encephalopathy, infection, autoimmune disorders, vitamins deficiency, inflammation, coagulopathy, or hereditary ataxias. The urine test results for illicit drug metabolites were negative. The cerebrospinal fluid (CSF) examination revealed normal cell count (3/mm) and glucose concentration (61 mg/dL), slightly raised total protein (55 mg/dL), IgG-index 0.46, in the absence of oligoclonal bands. Brain imaging (computed tomography (CT) and magnetic resonance imaging (MRI)) and neurophysiology tests were also normal. The patient was treated with supportive measures and was discharged after a month of hospitalization. At that time, he was stabilized to a clinical state characterized by normal level of consciousness and a severe pancerebellar syndrome with symmetric ataxia of gait and stance, dysarthria with ‘‘scanning’’ speech, terminal tremor, vertical nystagmus, dysmetria, dyskinesia, dysdiadochokinesia, and dyssynergia. He could stand, walk, or eat only if assisted and had a ranking scale score of 4.

Disseminated intravascular coagulation as the laboratory hallmark of acute Q fever

A 37-y-old white male presented with high fever, constitutional symptoms, mild meningeal and pulmonary involvement. Laboratory investigation revealed thrombocytopenia and excessive prolongation of coagulation times (International normalized ratio-INR- up to 6) requiring transfusion with 14 units of fresh frozen plasma. Serology established acute Coxiella burnetti infection. Patient recovered on levofloxacin.