Interferon alpha-induced hashimoto thyroiditis followed by transient graves disease in a patient with chronic HCV infection.

The case of a 37-year-old man with chronic hepatitis C virus (HCV) infection is presented. The patient had received a 6-month course of antiviral therapy with peg interferon alpha-2a and ribavirin, with concomitant clearance of hepatitis C virus ribonucleic acid (HCV-RNA) from serum at the end of treatment. Three months after the treatment course he developed clinical and laboratory features of hypothyroidism along with high titers of thyroid peroxidase antibodies. Later on, while on treatment with levothyroxine, he developed all the clinical features of Graves disease along with increased levels of thyroid stimulating hormone (TSH)-receptor antibodies.This patient exhibited a rare sequence of immune-mediated thyroid disorders as a result of interferon alpha treatment. At the end of treatment, the patient developed Hashimoto thyroiditis, a typically Th1-response-mediated disease, followed sequentially after 6 months by Graves disease, a typically Th2-response-mediated disorder. Although both clinical entities have been described in patients receiving interferon-based regimens, to our knowledge, the changing pattern of immune-mediated thyroid disease in the same individual has not been reported in the literature.

Granulocyte colony stimulating factor in HCV genotype-1 patients who develop Peg-IFN-alpha2b related severe neutropenia: a preliminary report on treatment, safety and efficacy.

Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.

Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease.

AIM: Retinol-binding protein-4 (RBP4) has been proposed as a new adipokine that regulates insulin action in muscles and the liver, and contributes to the pathogenesis of insulin resistance. As non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, we aimed to evaluate RBP4 levels in the serum and liver of patients with NAFLD. METHODS: Serum RBP4 was measured in 30 NAFLD patients and 30 matched healthy controls. RBP4 expression in the liver of NAFLD patients was shown by immunohistochemistry. RESULTS: Serum RPB4 was significantly lower in NAFLD patients compared with controls (25.15 vs 34.66 microg/mL, P < 0.001) and there was no correlation with metabolic parameters or insulin resistance. RBP4 liver tissue immunostaining was more extensive and intense in NAFLD liver compared with normal liver and the RBP4 immunohistochemical score was positively correlated with the grade of steatosis, grade of non-alcoholic steatohepatitis activity and stage of fibrosis. CONCLUSIONS: In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.

Methanogenic capacity and robustness of hydrogenotrophic cultures based on closed nutrient recycling via microbial catabolism: Impact of temperature and microbial attachment.

A biological methanation system based on nutrient recycling via mixed culture microbial catabolism was investigated at mesophilic (37 °C) and thermophilic (55 °C) temperatures. At mesophilic temperatures, the formation of biofilms on two different types of material was assessed. Results showed that with intense mixing the biofilm reactors presented methanogenic capacities (per working volume) 50% higher than the ones operated with suspended cultures. Gas feeding rates of 200 L/L/d were achieved at a H2/CO2 to CH4 conversion efficiency of above 90% by linking two reactors in series. Furthermore the robustness of the cultures was assessed under a series of inhibitory conditions that simulated possible process interferences at full scale operation. Full recovery after separate intense oxygenation and long starvation periods was observed within 2-5 days.

Closed nutrient recycling via microbial catabolism in an eco-engineered self regenerating mixed anaerobic microbiome for hydrogenotrophic methanogenesis.

A novel eco-engineered mixed anaerobic culture was successfully demonstrated for the first time to be capable of continuous regeneration in nutrient limiting conditions. Microbial catabolism has been found to support a closed system of nutrients able to enrich a culture of lithotrophic methanogens and provide microbial cell recycling. After enrichment, the hydrogenotrophic species was the dominating methanogens while a bacterial substratum was responsible for the redistribution of nutrients. q-PCR results indicated that 7% of the total population was responsible for the direct conversion of the gases. The efficiency of H2/CO2 conversion to CH4 reached 100% at a gassing rate of above 60v/v/d. The pH of the culture media was effectively sustained at optimal levels (pH 7-8) through a buffering system created by the dissolved CO2. The novel approach can reduce the process nutrient/metal requirement and enhance the environmental and financial performance of hydrogenotrophic methanogenesis for renewable energy storage.

Integration of Power to Methane in a waste water treatment plant - A feasibility study.

The integration of a biomethanation system within a wastewater treatment plant for conversion of CO2 and H2 to CH4 has been studied. Results indicate that the CO2 could be utilised to produce an additional 13,420m3/day of CH4, equivalent to approximately 133,826kWh of energy. The whole conversion process including electrolysis was found to have an energetic efficiency of 66.2%. The currently un-optimised biomethanation element of the process had a parasitic load of 19.9% of produced energy and strategies to reduce this to <5% are identified. The system could provide strategic benefits such as integrated management of electricity and gas networks, energy storage and maximising the deployment and efficiency of renewable energy assets. However, no policy or financial frameworks exist to attribute value to these increasingly important functions.

Aspartate aminotransferase to platelet ratio index for fibrosis evaluation in chronic viral hepatitis.

OBJECTIVE: We assessed the value of the recently developed aspartate aminotransferase to platelet ratio index (APRI) for predicting significant fibrosis or cirrhosis in patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B. METHODS: In total, 489 patients (chronic hepatitis C, 284 patients; HBeAg-negative chronic hepatitis B, 205 patients) were included. APRI values of 0.50 or less and greater than 1.50 were evaluated for predicting significant fibrosis, and APRI values of 1.00 or less and greater than 2.00 for predicting cirrhosis. Liver biopsies were evaluated according to the Ishak's classification. Fibrosis was considered to be significant in cases with scores 3-6, and cirrhosis to be present in cases with fibrosis scores of 5 and 6. RESULTS: Significant fibrosis was observed in 56/148 (38%) patients with APRI< or = 0.50, 130/227 (57%) patients with 0.501.50 (P<10). Cirrhosis was observed in 47/311 (15%) patients with APRI< or = 1.00, 29/93 (31%) patients with 1.002.00 (P<10). The areas under receiver-operating characteristic curves were 0.65 and 0.70 for prediction of significant fibrosis or cirrhosis, respectively. The combination of APRI< or = 0.50 and APRI>1.50 classified correctly 36% of patients with or without significant fibrosis, while the combination of APRI< or = 1.00 and APRI>2.00 classified correctly 62% of patients with or without cirrhosis. There was no significant difference in the predictive values of APRI between patients with chronic hepatitis C and chronic hepatitis B. CONCLUSIONS: APRI is significantly associated with the extent of fibrosis, but it does not classify correctly 40-65% of patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B, and thus it cannot replace liver biopsy.

Pseudohyperkalemia in patients with increased cellular components of blood.

OBJECTIVE: We performed a study to investigate the difference between serum and plasma potassium concentration in patients with increase in one or more of the cellular components of blood. DESIGN AND METHODS: This study was performed in two phases. During the first phase, we performed a cross-sectional comparison of the difference between serum and plasma potassium concentration (Dk) in 341 patients with the various clinical conditions where pseudohyperkalemia has been described, as well as with secondary or spurious erythrocytosis and in 30 normal controls. A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated. In the second phase we studied the significance of this cut-off value as predictor of polycythemia vera in 90 naive patients who were referred with an elevated hematocrit. RESULTS: Dk was significantly increased in the groups with platelet, erythrocyte or with a mixed type disorder compared to the controls (P < 0.01). Among these groups, Dk was significantly increased in the groups with thrombocytosis and mixed type disorder, compared to the group with erythrocytosis (both P < 0.01). A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated (0.70 mmol/L). Dk (> or = 0.70 mmol/L), platelet and white blood cell count were identified as significant independent predictors of polycythemia vera. CONCLUSIONS: The Dk is increased in patients with erythrocytoses, thrombocytoses or both. This phenomenon is more profound in patients with a mixed type disorder, such as polycythemia vera patients, compared to those with erythrocytoses alone.

Changes of liver and muscle enzymes activity in patients with rigor.

AIM: We investigated whether changes of liver and muscle enzymes activity are associated with rigor of several causes and have any prognostic significance. METHODS: Seventy-five patients with rigor were prospectively evaluated. Serum enzymes were measured at the onset of rigor and during the three following days. RESULTS: Causes of rigor were bacteremia (n=28), cholangiitis (n=12), protozoan infections (n=9), viral infections (n=10) and platelet transfusions (n=16). Increases in enzymes activity were observed with rigors from infectious causes, but not with that following platelet transfusions. Patients with cholangiitis demonstrated the highest ALT elevations, while those with viral infections the highest CPK levels. In bacteremia, CPK values increased significantly only in cases with dehydration and hypokalemia. CONCLUSIONS: Rigor per se does not cause increases in muscle or liver enzymes activities. Rather these changes are associated with the rigor's causative agent (infectious or not), the patient's general condition and the severity and extent of the underlying disease.

Hepatic steatosis in genotype 4 chronic hepatitis C is mainly because of metabolic factors.

BACKGROUND/AIM: Hepatic steatosis is considered to be mostly associated with viral factors in genotype 3 and metabolic factors in genotype 1 chronic hepatitis C, while there are rather few data for genotype 4. We determined the parameters associated with steatosis in 350 chronic hepatitis C patients, focusing on genotype 4. METHODS: Histological lesions were evaluated according to Ishak's classification and steatosis was semiquantitatively graded. Several patient characteristics on the biopsy day were also evaluated. RESULTS: Steatosis was present in 73% of patients without significant differences among genotypes. Moderate/severe steatosis was more frequent in genotype 3 than 4 (44% vs 26%, P= 0.025) and similar between genotype 4 and 1 patients. Moderate/severe steatosis was associated with body mass index (BMI) in genotype 4 (P= 0.023) and gamma-glutamyl-transpeptidase in genotype 3 patients (P= 0.044). In 150 nondiabetic patients with BMI < or =25 kg/m(2), moderate/severe steatosis was present in 15, 40, and 11% of genotype 1, 3, and 4 patients, respectively, (P= 0.005) and was independently associated only with genotype 3. In multivariate analysis, steatosis grade or moderate/severe steatosis was independently associated with higher BMI, genotype 3, and lower cholesterol. CONCLUSIONS: Moderate or severe steatosis is significantly less frequent in genotype 4 than 3 chronic hepatitis C patients and similar between genotype 4 and 1. In nondiabetic, nonoverweight patients, moderate or severe steatosis is present in only 10-15% of genotype 4 or 1 compared with 40% of genotype 3 patients. Thus, hepatic steatosis in genotype 4 is mostly associated with metabolic factors, similar to those in genotype 1.

Cholestasis in acute stroke: an investigation on its prevalence and etiology.

OBJECTIVE: Liver cholestatic enzymes and/or bilirubin occasionally occur in acute stroke and are usually, but not always, ascribed to comorbid conditions. We investigated the frequency and possible etiology of this phenomenon. MATERIAL AND METHODS: Prospective evaluation of post-admission biochemical cholestasis of all patients hospitalized with acute stroke was conducted during a 21-month period. RESULTS: Of 169 consecutive patients, 18 (10.7%) developed cholestasis. In 7 of the patients (4.1%; 4 M, 3 F, median age 70 years, range 57-82 years) no apparent cause of cholestasis could be found, and they were further evaluated (Group A). These patients were compared with 21 randomly selected stroke patients without cholestasis, matched for age and gender, and who acted as controls (Group B). Group A patients were in a deeper coma than the controls (Glasgow Coma Scale 3.4 +/- 0.8 versus 1.9 +/- 0.7, p < 0.001), associated with severe autonomic and hypothalamic involvement, while no such manifestations were present in Group B (p < 0.001). Cholestasis started on the 3rd-6th day and lasted up to the 11th-25th day, with maximum median levels of gamma-GT and serum alkaline phosphatase (SAP) of up to 4.38 (range 2.33-8.25) and 1.49 (range 0.63-2.56) times the upper limit of normal, respectively. Serum alanine aminotransferase (ALAT), total and direct bilirubin increased in Group A but not in Group B. The common bile duct was significantly wider in Group A than in Group B (7.7 +/- 0.5 versus 4.7 +/- 0.6 mm, p < 0.001) and within Group A during and after cholestasis (7.7 +/- 0.5 versus 4.7 +/- 0.5 mm, p < 0.001). CONCLUSIONS: Transient cholestasis may occur in 4.1% of patients following acute stroke. Cholestasis is associated with deeper coma, autonomic and hypothalamic involvement and common bile duct dilatation without obstruction, possibly related to inordinate hypertonia of the sphincter of Oddi.