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1.
Hematol Oncol ; 37(4): 434-437, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31465530

ABSTRACT

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan-Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET-t prognostic score or the current stratification for the thrombotic risk, high-risk patients are always highly represented. This evidence is of note, being the high-risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high-risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow-up of ET despite current recommendations, having a significant impact on morbidity and survival.


Subject(s)
Severity of Illness Index , Thrombocythemia, Essential/complications , Thrombophilia/etiology , Thrombosis/etiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Calreticulin/genetics , Female , Follow-Up Studies , Humans , Incidence , Janus Kinase 2/genetics , Kaplan-Meier Estimate , Male , Middle Aged , Models, Biological , Mutation, Missense , Prognosis , Receptors, Thrombopoietin/genetics , Recurrence , Retrospective Studies , Risk Assessment/methods , Risk Factors , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/mortality , Thrombophilia/genetics , Thrombosis/epidemiology , Young Adult
2.
J Biol Regul Homeost Agents ; 27(1): 233-9, 2013.
Article in English | MEDLINE | ID: mdl-23489702

ABSTRACT

The role of innate immune response mediated by Toll-like receptors in HCV infection, is not yet well understood and there is a lack of data regarding liver tissue expression of these molecules in chronic hepatitis C (CHC). Our study is aimed to investigate ex vivo, liver expression of TLR2, TLR3 and TLR7, which are more involved in the immune-pathogenesis of CHC, and to explore possible correlations with features of disease. We obtained liver biopsies and collected peripheral blood mononuclear cells (PBMC) from 23 consecutive patients with CHC and from 6 patients of control, without liver disease, undergoing surgery for cholecystectomy. The levels of TLRs mRNA in the samples were determined using a real-time reverse transcription quantitative PCR (RT-qPCR). We found a significant high expression of TLR3 in the liver of CHC patients respect to controls (also higher than expression in the PBMC). Conversely no differences emerged in the TLR2 and TLR7 levels between cases and controls. Also we found a correlation of TLR2 and TLR7 levels with the grade of necro-inflammation in the liver. Furthermore TLR7 hepatic levels resulted related to a more advanced stage of liver fibrosis. Ours is the first study to provide data on tissue expression of TLRs during chronic hepatitis C and we believe that it could lead to a better understanding of the role of these molecules in the HCV-mediated liver damage.


Subject(s)
Hepatitis C, Chronic/metabolism , Liver/metabolism , Liver/pathology , Toll-Like Receptors/metabolism , Case-Control Studies , Female , Hepatitis C, Chronic/genetics , Humans , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Toll-Like Receptors/genetics
3.
J Endocrinol Invest ; 36(4): 267-79, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23448968

ABSTRACT

Bariatric surgery is nowadays an effective therapeutic option for morbid obesity. Endocrinologists may thus have a growing opportunity to diagnose and treat obese patients eligible for surgery in pre- and post-operative phase. This requires a better understanding of endocrine changes caused by either obesity or weight loss surgery. Despite the large number of studies available in literature, only limited well-designed clinical trials have been performed so far to investigate changes of endocrine axes following bariatric procedures. There are still areas of unclear results such as female and male fertility, however, weight loss after bariatric surgery is considered to be associated with favorable effects on most endocrine axes. The aim of this clinical review is to overview the available literature on the effects of weight loss after bariatric surgery on the endocrine systems to suggest the most appropriate pre- and post-operative management of obese patients undergoing bariatric surgery in terms of "endocrine" health.


Subject(s)
Bariatric Surgery , Endocrine System/physiology , Obesity, Morbid/physiopathology , Obesity, Morbid/surgery , Adult , Bariatric Surgery/methods , Bariatric Surgery/rehabilitation , Diabetes Mellitus/blood , Diabetes Mellitus/metabolism , Diabetes Mellitus/physiopathology , Female , Humans , Male , Obesity, Morbid/blood , Obesity, Morbid/metabolism , Postoperative Period , Weight Loss/physiology
4.
G Ital Nefrol ; 40(3)2023 Jun 29.
Article in Italian | MEDLINE | ID: mdl-37427907

ABSTRACT

There is a strong correlation between SARS-CoV-2 and the onset of autoimmune neurological disease with atypical clinical presentation, characterized by limited response to medical therapy, likely caused by the underlying mechanism of the virus itself. In situations like these, after the failure of pharmacological therapy, therapeutic apheresis, including immunoadsorption, can be pursued. Treatments with IMMUSORBA TR-350 columns have proven to be particularly effective in managing refractory forms of post-Covid-19 nephropathies, leading to complete recovery of disability and elimination of neurological signs and symptoms. We discuss the case of a patient with chronic inflammatory polyradiculopathy post-Covid-19, resistant to medical therapy, effectively treated with immunoadsorption.


Subject(s)
Blood Component Removal , COVID-19 , Kidney Diseases , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , COVID-19/complications , COVID-19/therapy , SARS-CoV-2
5.
Int J Immunopathol Pharmacol ; 25(1): 293-6, 2012.
Article in English | MEDLINE | ID: mdl-22507344

ABSTRACT

The role played by HCV in the genesis of many autoimmune disorders has been reported in several studies. In particular, the onset of arthritis has been described in about 2-3 percent of HCV infection cases. At present, this HCV-related arthritis is classified as a reactive arthritis, but a real distinction of this form from classical rheumatoid arthritis is often difficult. In this presentation, the Authors distinguish two arthritic forms observed in HCV-related arthritis patients: one, characterized by asymmetrical oligoarticular-involvement, and another, with poly-articular symmetrical involvement. The Authors suggest that the latter can be considered as a form of rheumatoid arthritis, because of the similarity of the main clinical aspects and laboratory findings (rheumatoid factor, anti-cyclic citrullinated peptide antibodies) to those of classical rheumatoid arthritis, which make the two forms indistinguishable. Therefore, HCV could be considered the etiologic agent of a limited number of cases of rheumatoid arthritis.


Subject(s)
Arthritis, Infectious/etiology , Arthritis, Rheumatoid/etiology , Hepatitis C/complications , Adult , Aged , Female , Humans , Interferon-gamma/blood , Male , Middle Aged , Rheumatoid Factor/physiology
6.
Int J Immunopathol Pharmacol ; 25(1): 281-5, 2012.
Article in English | MEDLINE | ID: mdl-22507342

ABSTRACT

The high serum levels of Interleukin-6 (IL-6) and its soluble receptors (sIL-6r and sgp130), described in the course of Rheumatoid Arthritis (RA), have been linked to the enhanced activity of this cytokine in this disorder. In this study, the serum concentrations of IL-6 and its soluble receptors were determined in a group of patients with HCV-related arthritis (HCVrA), a condition resembling RA in several aspects, and then compared to those found in a sample of subjects affected by RA. Twenty-one patients with HCVrA, 24 patients with RA and 20 healthy subjects (control group) were examined. Different ELISA methods were used for determination of serum concentrations of IL-6, sIL-6r and sgp130. Increased IL-6 serum levels were found in 15 (71 %) of the patients with HCVrA and in 16 (62 %) of those with RA. Eight (38 %) of the patients with HCVrA and 11 (46%) of those with RA denoted high levels of sIL-6r, while sgp130 levels were elevated in 21 (76%) of the patients with HCVrA and in 16 (69%) of those with RA. A significant difference between the median values of sIL-6r and sgp130 levels in the two groups of patients versus controls was found. A mild correlation of these parameters with RF levels was detected in the RA group. Furthermore, in HCVrA patients the serum levels of IL-6, sIL-6r and sgp130 appeared unrelated to HCV viraemia and to levels of transaminases. The enhanced serum levels of IL-6 in HCVra patients indicate an increased synthesis and hyperactivity of this cytokine in HCVrA, and the substantial similarity of the behaviour of IL-6 and its serum receptors in the two groups of patients suggests common mechanisms with RA, in which the function of I L-6 is central.


Subject(s)
Arthritis, Infectious/immunology , Arthritis, Rheumatoid/immunology , Hepatitis C/complications , Interleukin-6/blood , Receptors, Interleukin-6/blood , Adult , Arthritis, Infectious/etiology , Female , Humans , Interleukin-6/physiology , Male , Middle Aged , Pilot Projects
7.
J Physiol Pharmacol ; 73(1)2022 Feb.
Article in English | MEDLINE | ID: mdl-35639037

ABSTRACT

Risk factors for Peyronie's disease (PD) are serum lipid abnormalities, hypertension and type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation are key-players in the pathogenesis of arterial diseases, leading to insulin resistance (IR), which is a major determinant of non-alcoholic fatty liver disease (NAFLD). We studied the potential relationship between PD, IR, and NAFLD. Forty-nine male patients were enrolled, fulfilling the well-accepted diagnostic criteria of stable PD. Fifty male individuals without PD, well-matched for age and BMI, were selected as the control group. Comorbidities (T2DM and hypertension), as well as the lipid profile and the glucometabolic asset, were evaluated. The triglycerides/HDL ratio (TG/HDL-C ratio) with a cut-off of ≥3 and the triglycerides-glucose index (TyG) with an optimal cut-point of 8.5 were used for diagnosis of IR and NAFLD, respectively. NAFLD diagnosis was confirmed by the presence of bright liver at ultrasonography. Hypertension was found more frequently in PD patients than in no-PD subjects (P=0.017), independently of age (P=0.99). Both IR and NAFLD were significantly associated with the presence of PD in our population of men (P=0.043 and 0.0001, respectively), no matter how old (P=0.11 and 0.74, respectively). At logistic regression, NAFLD was the only predictor of the PD presence (p=0.021). The AUROC of TyG to predict PD was 0.7437 (sensitivity 67.35% and specificity 80%) with a percentage of correctly classified patients of 73.74%. Oxidative stress markers were significantly associated with NAFLD. Testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses. Both factors, i.e., oxidative stress and hypogonadism, are central to PD pathogenesis. In conclusion, NAFLD and IR are strongly associated with PD. The pathogenic link between these conditions and the underlying mechanisms are only hypothetical and thoroughly summarized in the discussion.


Subject(s)
Diabetes Mellitus, Type 2 , Hypertension , Insulin Resistance , Non-alcoholic Fatty Liver Disease , Penile Induration , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Glucose , Humans , Male , Penile Induration/complications , Pilot Projects , Triglycerides
8.
Transpl Infect Dis ; 13(5): 501-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21414117

ABSTRACT

Although human immunodeficiency virus (HIV) infection has been a major global health problem for almost 3 decades, with the introduction of highly active antiretroviral therapy in 1996 and effective prophylaxis and management of opportunistic infections, mortality from acquired immunodeficiency syndrome has decreased markedly. In developed countries, this condition is now being treated as a chronic condition. As a result, rates of morbidity and mortality from other medical conditions leading to end-stage liver, kidney, and heart disease are steadily increasing in individuals with HIV. Because the definitive treatment for end-stage organ failure is transplantation, the demand for it has increased among HIV-infected patients. For these reasons, many transplant centers have eliminated HIV infection as a contraindication to transplantation, as a result of better patient management and demand.


Subject(s)
HIV Infections/complications , Kidney Transplantation , Liver Transplantation , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Humans , Liver Failure/therapy , Male , Middle Aged , Patient Selection , Renal Insufficiency/therapy , Treatment Outcome
9.
J Biol Regul Homeost Agents ; 25(1): 47-56, 2011.
Article in English | MEDLINE | ID: mdl-21382273

ABSTRACT

Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.


Subject(s)
Bilirubin/blood , Cytochromes c/blood , Obesity/blood , Triglycerides/blood , gamma-Glutamyltransferase/blood , Adolescent , Adult , Biomarkers/blood , Cross-Sectional Studies , Fatty Liver/blood , Fatty Liver/diagnostic imaging , Female , Humans , Male , Mitochondria/metabolism , Non-alcoholic Fatty Liver Disease , Obesity/diagnostic imaging , Oxidative Stress , Retrospective Studies , Ultrasonography
10.
J Biol Regul Homeost Agents ; 25(4): 647-54, 2011.
Article in English | MEDLINE | ID: mdl-22217996

ABSTRACT

Systemic sclerosis (SSc) is a chronic disease of connective tissue characterized by vascular damage, autoantibody production and extensive fibrosis of skin, skeletal muscles, vessels and visceral organs. Fibrosis is a biological process involving inflammatory response and reactive oxygen species (ROS) accumulation leading to fibroblast activation. Extracellular superoxide dismutase (SOD3), a copper and zinc superoxide dismutase, which is expressed in selected tissues, is secreted into the extracellular space and catalyzes the dismutation of superoxide radical to hydrogen peroxide and molecular oxygen. Moreover, SOD3 is associated to inflammatory responses in some experimental models. In this paper we analysed, by RT-PCR and immunofluorescence, SOD3 expression and intracellular localization in dermal fibroblasts from both healthy donors and patients affected by diffuse form of SSc. Moreover, we determined SOD3 enzymatic activity in fibroblast culture medium with the xanthine/xanthine oxidase method. Increased expression of SOD3 mRNA was detected in systemic sclerosis fibroblasts (SScF), as compared to control healthy fibroblasts (HF), and SOD3 immunofluorescence staining displayed a characteristic pattern of secretory proteins in both HF and SScF. Superoxide dismutase assay demonstrated that SOD3 enzymatic activity in SScF culture medium is four times more than in HF culture medium. These data suggest that an alteration in SOD3 expression and activity could be associated to SSc fibrosis.


Subject(s)
Fibroblasts/enzymology , Scleroderma, Systemic/enzymology , Superoxide Dismutase/genetics , Adult , Female , Fluorescent Antibody Technique , Humans , RNA, Messenger/analysis , Superoxide Dismutase/analysis , Superoxide Dismutase/metabolism
11.
Int J Immunopathol Pharmacol ; 23(4): 1303-8, 2010.
Article in English | MEDLINE | ID: mdl-21244785

ABSTRACT

Immunosuppression has improved graft and recipient survival in transplantation but is associated with possible adverse effects including cardiovascular diseases. The impact of tacrolimus on the lipidic profile has been debated for several years. Twenty-nine kidney transplant recipients on tacrolimus treatment were monitored for six years, and multiple laboratory parameters investigating the lipid asset, as well as glucose profile, were carried out. Tacrolimus has been responsible for significant changes in plasma lipid concentrations only for the first six months, but not for the remaining time of observation. Similarly, in the same periods, glycemic imbalance was highlighted. The liver enzyme activity showed a modest derangement during the tacrolimus treatment, suggesting the presence of lipid accumulation in the liver. Fatty liver reversed in the long term follow-up. Tacrolimus, although it is not a completely safe option in the first months of the immunosuppressive protocols in organ transplanted recipients, still retains a certain role in the long-term post-transplantation immunosuppressive approach with high cardiovascular risks.


Subject(s)
Fatty Liver/etiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation , Lipids/blood , Tacrolimus/adverse effects , Adult , Female , Humans , Male , Middle Aged , Time Factors
12.
J Clin Pharm Ther ; 35(1): 121-4, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20175821

ABSTRACT

Infection occurs frequently in the organ transplant recipients during the post-transplant period because of immunosuppression. Therefore, prophylactic antimicrobial agents are often used. The azole antifungals, widely prescribed prophylactically, are known to have many drug-drug interactions. This report presents a case of drug-drug interaction between voriconazole and tacrolimus in a kidney transplant recipient. Voriconazole treatment led to a dramatic increase in tacrolimus concentration that required its discontinuation in spite of the manufacturer's guidelines that recommend a reduction of tacrolimus dosage by one-third. The present drug-drug interaction can be attributed to a strong inhibitory effect on cytochrome P450-3A4 activity by voriconazole. When voriconazole and tacrolimus are coadministered, close monitoring of tacrolimus blood levels is recommended as the rule-of-thumb reduction of tacrolimus dose by one-third may not be satisfactory.


Subject(s)
Antifungal Agents/therapeutic use , Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation , Pyrimidines/therapeutic use , Tacrolimus/pharmacokinetics , Triazoles/therapeutic use , Adult , Cytochrome P-450 CYP3A , Cytochrome P-450 CYP3A Inhibitors , Drug Interactions , Drug Monitoring , Drug Therapy, Combination , Enzyme Inhibitors/therapeutic use , Female , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/therapy , Tacrolimus/blood , Tacrolimus/therapeutic use , Treatment Outcome , Voriconazole
13.
J Viral Hepat ; 16(6): 397-405, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19200135

ABSTRACT

B-lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor-family cytokine that plays a key role in generating and maintaining the mature B-cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon-gamma and interleukin-10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 +/- 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at baseline (within 4 weeks of onset) and during follow-up. BLyS/BAFF median levels were significantly higher in AHC (1485 pg/mL) than in CHC (1058 pg/mL) and in HBD (980 pg/mL) (P < 0.001). BLyS/BAFF levels were higher in AHC patients evolving to chronicity (1980 pg/mL) than in those with a self-limited course (1200 pg/mL), (P = 0.02). By logistic regression analysis, higher BLyS/BAFF levels were independently associated with persistence of HCV infection (OR 29.7; 95% CI: 1.73-508.20). High serum levels of BLyS/BAFF at onset of AHC can predict its evolution to chronic infection.


Subject(s)
B-Cell Activating Factor/blood , Hepatitis C/immunology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Female , Hepatitis C, Chronic/immunology , Humans , Male , Middle Aged , Young Adult
14.
Int J Immunopathol Pharmacol ; 22(2): 531-5, 2009.
Article in English | MEDLINE | ID: mdl-19505406

ABSTRACT

Hepatitis B virus (HBV) infection is known to be responsible for both hepatic and extrahepatic manifestations including dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extrahepatic disorders is thought to be linked to immune complex disease, but their pathogenesis is poorly clarified. Immunosuppressive treatment could promote viral load and impair hepatic disease, also worsening the vasculitis by enhancing viral antigenemia. Lamivudine is a nucleoside analogue approved for treating chronic hepatitis B, that decreases the amount of viral antigens by suppressing HBV replication. Several reports have suggested lamivudine in the treatment of vasculitis associated with HBV infection, but, although significant inhibition of HBV is achieved in the short term, resistance develops in 15-32 percent annual risk rating. We report an elderly patient whose chronic hepatitis B decompensated cirrhosis with associated refractory hepatic hydrothorax and extensive leukocytoclastic vasculitis was successfully treated with ongoing long-term lamivudine monotherapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Liver Cirrhosis/virology , Vasculitis, Leukocytoclastic, Cutaneous/virology , Aged, 80 and over , DNA, Viral/blood , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/immunology , Humans , Hydrothorax/drug therapy , Hydrothorax/virology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/immunology , Male , Treatment Outcome , Vasculitis, Leukocytoclastic, Cutaneous/drug therapy , Vasculitis, Leukocytoclastic, Cutaneous/immunology , Viral Load , Virus Replication/drug effects
15.
Int J Immunopathol Pharmacol ; 22(4): 1009-17, 2009.
Article in English | MEDLINE | ID: mdl-20074464

ABSTRACT

As the lymphotropism of hepatitis C virus (HCV) has already been ascertained, and in the light of the fact that the immune defense system is an organized network composed of functionally interrelated tissues, this study was carried out to verify the possible involvement of spleen in HCV-related chronic hepatitis. In this cross-sectional study we measured spleen longitudinal diameter by ultrasound, beta2-microglobulin serum levels and splenic artery resistivity index (SARI) by Doppler in 51 patients treated with standard combined (Peg-Interferon plus Ribavirin) antiviral therapy. Thirty-three patients (17 females) completed the regimen and were compared to 31 controls (16 females). The mean basal values of spleen longitudinal diameter were higher in patients with chronic hepatitis than in controls, i.e., 116 mm (9.4) versus 102.7 mm (9.3), P = 0.0001. In the same patients a significant trend towards increased spleen longitudinal diameter was found after antiviral therapy, independently of the stage of HCV-related chronic hepatitis. The median values of the beta2-microglobulin concentrations were not significantly higher in the patients with HCV-related chronic hepatitis compared to controls, i.e., 1.3 (0.5-2.6) versus 1 (0.6-1.4), P = 0.16, although during the course of therapy they were significantly increased. SARI values of HCV-related chronic hepatitis patients were different from those of controls, but were unvaried compared to values at the end of treatment. Neither spleen measurements nor serum beta2-microglobulin levels were able to predict therapeutic response to antiviral therapy. A stimulation/expansion of lymphoid tissue was found in patients with HCV-related chronic hepatitis. Such evidence raises the question whether physicians should continue to prescribe antiviral therapy in non-responders and supports the use of a new scheme (SLD plus beta2-MG) to diagnose this ongoing, apparently reversible, but nevertheless dangerous immunologic process.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Spleen/drug effects , Adult , Antiviral Agents/adverse effects , Biomarkers/blood , Cross-Sectional Studies , Drug Therapy, Combination , Female , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/diagnostic imaging , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Middle Aged , Organ Size , Polyethylene Glycols/adverse effects , Prospective Studies , Recombinant Proteins , Ribavirin/adverse effects , Spleen/blood supply , Spleen/diagnostic imaging , Spleen/virology , Splenic Artery/diagnostic imaging , Treatment Outcome , Ultrasonography, Doppler , Vascular Resistance , Young Adult , beta 2-Microglobulin/blood
16.
J Endocrinol Invest ; 32(6): 525-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19474520

ABSTRACT

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.


Subject(s)
Adiponectin/metabolism , Ion Channels/genetics , Leptin/metabolism , Mitochondrial Proteins/genetics , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Adiponectin/blood , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Blood Glucose/analysis , Cholesterol/blood , Fatty Liver/blood , Fatty Liver/genetics , Fatty Liver/metabolism , Female , Humans , Insulin/blood , Ion Channels/metabolism , Italy , Leptin/blood , Male , Metabolic Syndrome/blood , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Middle Aged , Mitochondrial Proteins/metabolism , Obesity, Morbid/blood , Polymorphism, Single Nucleotide , Statistics, Nonparametric , Triglycerides/blood , Uncoupling Protein 1 , Young Adult , gamma-Glutamyltransferase/blood
17.
Transplant Proc ; 51(1): 187-189, 2019.
Article in English | MEDLINE | ID: mdl-30736972

ABSTRACT

BACKGROUND: Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. METHODS: We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. RESULTS: A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. CONCLUSIONS: The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.


Subject(s)
Alcoholism/diagnosis , Liver Cirrhosis, Alcoholic/surgery , Liver Transplantation , Patient Selection , Adult , Alcohol Abstinence , Female , Humans , Italy , Liver Transplantation/mortality , Male , Middle Aged , Patient Care Team , Recidivism , Recurrence , Retrospective Studies , Treatment Outcome , United States
18.
J Viral Hepat ; 15(7): 523-30, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18266647

ABSTRACT

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was observed in 46 patients (31%), and patients who consumed drugs had an odds ratio (OR) of 4.02 (95% CI: 1.62-9.96) to have an eosinophilic infiltrate in liver biopsy. By logistic regression analysis, the presence of steatosis was independently associated with eosinophilic infiltrate (OR 5.86; 95% CI: 2.46-13.96) and homeostasis model assessment-score (OR 1.18; 95% CI: 1.00-1.39). Logistic regression analysis also showed that fibrosis staging > or = 2 by Scheuer score was associated with grading >1 by Scheuer score (OR 6.82; 95% CI 2.46-18.80) and eosinophilic infiltrate (OR 4.00; 95% CI 1.23-12.91). In conclusion, we observed that the eosinophilic infiltrate of liver tissue was significantly more frequent in patients who assumed drugs, and found a significant association between eosinophilic infiltrate, liver steatosis and liver fibrosis. These preliminary data could lead to a constant assumption of drugs as a co-factor of eosinophils-mediated liver injury in chronic hepatitis C.


Subject(s)
Eosinophilia/pathology , Hepatitis C, Chronic/pathology , Eosinophils , Fatty Liver/etiology , Female , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/physiopathology , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/etiology , Male , Retrospective Studies
19.
J Viral Hepat ; 15(9): 646-50, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18507758

ABSTRACT

Depression is an usual finding in patients suffering from chronic hepatitis C. Development of moderate to severe depressive symptoms occurs frequently during pegylated interferon/ribavirin treatment and is generally predicted by baseline depression scores. Furthermore, the obese patients have been found to be twice as likely to suffer from anxiety, impaired social interaction, and depression when compared with the no obese population. In order to evaluate the efficacy of a pharmacological treatment of depression, 68 obese patients with chronic hepatitis C, under or not antiviral therapy, were selected and enrolled into this open, controlled pilot study. Our population was divided in two groups: 'on Selective Serotonin Reuptake Inhibitors plus support', with individual titration of medication to adequate side-effects, including thirty seven patients, and 'on only support', involving thirty one patients. Both groups were well balanced for gender, age and antiviral treatment. The selected patients had, at entry, a Beck Depression Inventory score of 24.5 +/- 8.1 (mean +/- SD). Therapeutic successful outcomes (a decreased score of >or= 10 units compared to the baseline) were statistically more frequent in antidepressant drug-treated group (P = 0.005); they were well predicted by dose of Selective Serotonin Reuptake Inhibitors. Thirty five percent of patients were non-responder to Selective Serotonin Reuptake Inhibitors. The drug tolerability was good. Nearly twenty percent of patients were responder to only support.


Subject(s)
Depression/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/psychology , Obesity/complications , Obesity/psychology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Case-Control Studies , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Pilot Projects , Selective Serotonin Reuptake Inhibitors/adverse effects , Severity of Illness Index
20.
Clin Exp Rheumatol ; 26(5): 926-8, 2008.
Article in English | MEDLINE | ID: mdl-19032831

ABSTRACT

Positivity of rheumatoid factor (RF) in the course of Hepatitis C virus HCV infection has been described in many papers, with percentages between 30% and 80%, but no data are reported on the behaviour of this parameter during the treatment. In the present retrospective study, 66 patients with HCV infection and positivity for RF were observed between March 2001 and January 2004; they had received combined therapy with Peg-IFN alpha-2b 1.5 mcg/kg/weekly and ribavirin 800-1200 mg/daily (on the basis of body weight). Before treatment, all of them had presented hypertransaminasemia for at least 6 months and high viral load. No patient suffered from other hypersensitivity disorders. The follow-up period lasted for a mean period of 26+/-7 months, after which only 34 (51.5%) revealed normal transaminases activity with negativity of HCV-RNA (long-term responders, LTR), while the remaining 32 (48.5%) were classified as non responders (NR). In both groups significant variations of RF values were observed. Moreover, RF remained positive in 6 (17.6%) of the LTR group and in 17 (53.1%) of the NR group patients. These data suggest a possible inhibiting action of the combined therapy on the exaggerated immune response. This effect appears partially unrelated to the antiviral action of the therapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Rheumatoid Factor/blood , Adult , Female , Follow-Up Studies , Hepatitis C, Chronic/blood , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Middle Aged , Polyethylene Glycols , Recombinant Proteins , Retrospective Studies , Ribavirin/therapeutic use , Viral Load
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