[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen.
Full-text · Article · Jun 2015 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: We aimed to verify whether CD4+/CD25+ T cells suppress CD4+ T cells and secrete Granzyme B (GZ-B) during acute and chronic hepatitis C (CHC) PATIENTS AND METHODS: We enrolled 50 subjects: 20 with CHC (Group A), 15 healthy individuals (Group B) and 10 patients with acute hepatitis C later evolved to persistent infection (Group C) and 5 patients who resolved HCV infection during acute phase (Group D). We analysed, on enrolled subjects CD4+/CD25+ T cells and related Granzyme B production as well as Annexin V activity.
Full-text · Article · Jun 2014 · Foodborne Pathogens and Disease
[Show abstract][Hide abstract] ABSTRACT: The assessment and monitoring of liver fibrosis (LF) is a key issue in the management and definition of prognosis of patients with chronic hepatitis C (CHC). In this respect, despite recognized limitations (invasive nature, sampling errors, interobserver variability, nondynamic evaluation of LF), liver biopsy is traditionally considered the reference standard. These limitations stimulated the search for noninvasive approaches for the assessment of LF, particularly attractive in patients with hemophilia and other congenital bleeding disorders (CBD). In patients with congenital bleeding disorders (CBD), who often suffer from CHC because of the past use of nonvirally inactivated plasma-derived products, the risk of bleeding hamper to routinely obtain histological data for LF staging. A variety of methods have been proposed and, in some cases, validated in patients with CHC and other liver diseases, including biomarkers directly or indirectly associated with LF, often combined in scores or algorithms, and the more recently developed physical approaches, evaluating the properties of the liver parenchyma with instrumental techniques studying the propagation of specific signals, that is, transient elastography (TE), acoustic radiation force impulse imaging elastography, and magnetic resonance elastography. This review will describe the available strategies for noninvasive assessment of LF, with more details on the latter promising instrumental approaches. Moreover, although lacking of validation against liver biopsy, recent studies extending the use of noninvasive methods (particularly TE) in the setting of patients with CBD will be discussed.
No preview · Article · Sep 2013 · Seminars in Thrombosis and Hemostasis
[Show abstract][Hide abstract] ABSTRACT: Pathogenesis of atherosclerosis involves multiple mechanisms, including imbalanced lipid metabolism, disturbed equilibrium of the immune response, and chronic inflammation of the artery wall. Several reports have shown a relationship between the development of atherosclerosis and the presence of infectious diseases, widely occurring in the general population, often chronic and/or asymptomatic. Beyond Chlamydia pneumoniae, a large number of infectious agents have been linked with an increased risk of vascular disease, with variable strength of supporting data: Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, herpes virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. Infections may contribute to atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at "nonvascular" sites. More recently, investigators reported that the aggregate burden ("infectious burden") of these chronic infections, rather than the effects of a single organism, might contribute to atherosclerosis and its thrombotic complications. However, the role of infection, as a proinflammatory cause of atherosclerosis, is still debated in the literature. This article will review available data suggesting a relationship between different infective pathogens and atherothrombosis, the hypothesized mechanisms, and the potential role for antimicrobial treatment.
No preview · Article · Jun 2012 · Seminars in Thrombosis and Hemostasis
[Show abstract][Hide abstract] 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.
No preview · Article · Jan 2011 · Journal of biological regulators and homeostatic agents
[Show abstract][Hide abstract] ABSTRACT: To identify which parameters could help to distinguish the "metabolically benign obesity", which is not accompanied by insulin resistance (IR) and early atherosclerosis.
Eighty two of 124 overweight/obese females formed the study population, which was divided into two groups (52 and 30 subjects, respectively) with and without IR according to a HO meostatic Metabolic Assessment (HOMA) cut-off of 2, and were studied in a cross-sectional manner. The main outcome measures were waist circumference, serum uric acid, high-density lipoprotein-cholesterol and triglycerides, alanine aminotransferase, blood pressure and the two imaging parameters, hepatic steatosis and longitudinal diameter of the spleen, which were measured in relation to the presence/absence of IR.
A variable grade of visceral obesity was observed in all subjects with the exception of three. Obesity of a severe grade was represented more in the group of IR individuals (P = 0.01). Hepatic steatosis, revealed at ultrasound, was more pronounced in IR than in non-IR subjects (P = 0.005). The two groups also demonstrated a clear difference in longitudinal spleen diameter and blood pressure, with raised and significant values in the IR group. Metabolic syndrome was frequent in the IR group, and was not modified when adjusted for menopause (P = 0.001). At linear regression, the beta values of waist circumference and body mass index predicting HOMA were 0.295, P = 0.007 and 0.41, P = 0.0001, respectively. Measures of spleen longitudinal diameter were well predicted by body mass index (BMI) values, beta = 0.35, P = 0.01, and by HOMA, beta = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, beta = 0.39, P = 0.0001). HOMA and hepatic steatosis were highly associated (rho = 0.34, P = 0.002). Interestingly, IR patients were almost twice as likely to have hepatic steatosis as non-IR patients. Among the MS criteria, blood pressure was very accurate in identifying the presence of IR (AUROC for systolic blood pressure 0.66, cut-off 125 mm of Hg, sensibility 64%, specificity 75%; AUROC for diastolic blood pressure 0.70, cut-off 85 mm of Hg, sensibility 54.5%, specificity 75%).
As health care costs are skyrocketing, reliable and mainly inexpensive tools are advisable to better define subjects who really need to lose weight.
Full-text · Article · Dec 2009 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications.
Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography.
The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66).
Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence.
Full-text · Article · Nov 2009 · BMC Gastroenterology
[Show abstract][Hide abstract] 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.
No preview · Article · Oct 2009 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ- and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. HCV infection of lymphoid cells could set up privileged reservoirs able to interfere with the host viral clearance efficiency and may be implicated in viral recurrence after apparently successful antiviral therapy. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, easily detectable by searching simple laboratory and clinical parameters, mainly represented by vasculitis-like skin features and hypocomplementemia. The presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identified as a novel immunological cofactor. Further research is required to fully verify the real impact on therapeutic choice/regimen.
Preview · Article · Jun 2009 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Nonalcoholic fatty liver disease describes a set of conditions that range from fatty liver to nonalcoholic steatohepatitis (NASH), and is considered the hepatic manifestation of metabolic syndrome. Obesity and insulin resistance are strongly associated with systemic markers of inflammation.
Focusing on this aspect, we have attempted to find a noninvasive method that could likely assess the presence of NASH and help to decide the liver biopsy performance.
Using histology as a gold standard to diagnose nonalcoholic fatty liver disease, we consecutively studied 43 patients with NASH and 40 with fatty liver, comparing their data with those of 48 healthy control participants. The outcomes evaluated were ultrasonographic spleen longitudinal diameter coupled with the splenic artery resistive index, serum IL-6 and vascular endothelial growth factor concentrations.
The NASH group had higher spleen longitudinal diameter values (P=0.0001) as well as significantly higher IL-6 and vascular endothelial growth factor concentrations than the other groups (P=0.0001). The optimal cut-off value for spleen longitudinal diameter that best discriminated NASH from fatty liver patients was 116 mm (specificity 95% and sensitivity 88%); the sensitivity and specificity of this parameter was better than both IL-6 and vascular endothelial growth factor in the same setting (area under the receiver operating characteristic curve 0.920 vs. 0.817 and 0.678). Splenic artery resistive index was similar between patients with NASH and those with fatty liver, but differed when compared with controls, P=0.0001.
IL-6 was highly specific in confirming the absence of NASH at normal values. In our series, normal values of spleen longitudinal diameter and IL-6 were strongly associated with fatty liver.
No preview · Article · Apr 2009 · European journal of gastroenterology & hepatology
[Show abstract][Hide abstract] 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.
No preview · Article · Apr 2009 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] ABSTRACT: Tissue Polypeptide Specific antigen has recently been proposed as diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis. The aim of this study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the clinical utility of this marker after different programs of weight reduction.
Overweight/obese patients with visceral adiposity and liver histology compatible were assigned to a Calorically-Restricted diet (n = 22), a Calorically-Restricted diet plus EXercise (n = 19) or No Healthy Life Style (control group, n = 21) for six months. The presence of Body-Weight loss was assessed by a Body Mass Index decrease of at least three points. Serum ALanine aminoTransferase, HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen concentrations were determined at time 0, after 3 and 6 months in both the Intervention groups and in the controls' one.
In NonAlcoholic SteatoHepatitis patients who obtained Body-Weight reduction, a significant decrease of the serum Tissue Polypeptide Specific antigen values was showed with a clear linear trend across time, P = 0.0001. Decrement of Tissue Polypeptide Specific antigen concentrations best differentiated the Body-Weight loss from the body-weight maintenance in respect to Tissue Polypeptide Specific antigen and HOmeostasis Model Assessment method values.
This study support the clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on weight reduction programs.
[Show abstract][Hide abstract] ABSTRACT: Obesity is a leading risk factor for metabolic syndrome whose further expression is non-alcoholic fatty liver disease. Metabolic syndrome is associated with a proinflammatory state that contributes to insulin resistance. Finally, a "metabolically benign obesity" that is not accompanied by insulin resistance has recently been postulated to exist.
To find whether any inflammation markers were independently associated with the presence of insulin resistance, evaluating specific anthropometric, ultrasonographic and laboratory parameters in a population of young adult obese subjects.
Of forty two young individuals, divided into two groups (with or without insulin resistance), were studied serum C-reactive protein and fibrinogen as indexes of chronic pro-inflammatory status. Body mass index, waist circumference and metabolic syndrome presence were assessed as part of the metabolic evaluation. Ultrasonography weighted visceral and subcutaneous abdominal fat thickness, spleen size as longitudinal diameter and liver hyperechogenicity.
Serum C-reactive protein and fibrinogen as well as spleen longitudinal diameter were significantly increased in the obese young with insulin resistance compared to non-insulin resistance group. Insulin resistance was significantly associated with hepatic steatosis score at sonography (r = 0.33, P = 0.03), spleen longitudinal diameter (r = 0.35, P = 0.02) and C-reactive protein (r = 0.38, P = 0.01), but not with body mass index, visceral or subcutaneous abdominal adipose tissue, waist circumference and fibrinogen (P = 0.18, 0.46, 0.33, 0.37 and 0.4, respectively). Steatosis score at sonography was well associated with spleen volume (rho = 0.40, P = 0.01) and C-reactive protein levels (rho = 0.49, P = 0.002). Metabolic syndrome was much more frequent in obese patients with insulin resistance. These findings show that in young adults the only abdominal adiposity without insulin resistance, plays a scarce role in determining hepatic steatosis as well as metabolic syndrome.
Increases in spleen size and CRP levels represent a reliable tool in diagnosing insulin resistance.
Full-text · Article · Feb 2009 · Journal of Inflammation
[Show abstract][Hide abstract] ABSTRACT: Inside the spectrum of non-alcoholic fatty liver disease, simple fatty liver is generally thought of as being "non progressive", differently from non-alcoholic steatohepatitis, which increases in severity due to the presence of apoptosis/inflammation and fibrosis. The "benignity" of fatty liver is widely accepted but conceptually difficult to maintain because the mechanisms underlying this entity are the same ones that determine the more severe form.
Findings provide evidence that iron overload is associated with increased liver damage and collagen deposition. Transforming growth factor-beta1 released by hepatic stellate cells during chronic liver injury plays a critical role in liver apoptosis and fibrogenesis.
To verify whether both the forms of non-alcoholic fatty liver disease were really dissimilar, evaluating the serum profile of two key parameters, indexes of severity.
A total of 123 patients (57 females) participated, forming three groups: forty five patients with fatty liver, 42 patients with non-alcoholic steatohepatitis and 36 with chronic hepatitis C. All had a biopsy-proven diagnosis.
Serum concentrations of transforming growth factor-beta1 and ferritin.
High concentrations of transforming growth factor-beta1 were noticed in patients suffering from both fatty liver and non-alcoholic steatohepatitis, 129.1 (45.4) versus 116.8 (42.2) ng/mL, P = 0.2; they were significantly superior to those of chronic hepatitis C patients 87.5 (39.5) ng/mL, P < 0.001. Ferritin levels were on average above normal values and similar in the three groups (P = 0.9), also when adjusted for gender (P = 0.5) and age (P = 0.3).
No difference between serum concentrations of transforming growth factor-beta1 and ferritin in fatty liver and non-alcoholic steatohepatitis suggests that these forms share more common aspects, regarding their progression, than previously thought.
Full-text · Article · Dec 2008 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: Congenital coagulation disorders limit the use of liver biopsy, especially when repeated assessment is needed. TGF-beta 1 plays a pivotal role in inducing fibrosis and has been proposed as its surrogate marker. Aiming at validating the clinical utility of this cytokine, fifteen haemophilic patients suffering from HCV-related chronic hepatitis were treated with Peg-IFN alpha2beta plus Ribavirin. Serum TGFbeta 1, viral load and liver enzymes were analyzed at baseline and at six, twelve, and eighteen months. As expected, patients initially showed significantly higher TGF-beta 1 levels than age-matched controls (43.8 ng/mL, 28.7-46.4 vs. 26.9 ng/mL, 23.0-34.0, median and 95% CI; p=0.004). The end of therapy response rate was 67%. The main finding was a significant drop in TGF-beta 1 at six months compared to baseline values; this drop de facto predicted the levels reached in the following six months, which were fixed at lower concentrations (37.0 ng/mL, 21.9-43.8 and 27.0 ng/mL, 24.1-44.0 respectively; p<0.009), independently of treatment outcome (three patients were breakthrough, twelve were sustained virological responders (SVRs). During the treatment period none had clinical or biochemical signs of inflammation in other areas. Treatment was followed by a six-month follow-up, at the end of which TGF-beta 1 was increased compared to the previous values, reaching the initial levels in ten SVRs (45 ng/mL, 24.5-52.9). Interestingly, at a longer follow-up, two out of ten SVRs, who displayed the highest values of TGF-beta 1, relapsed. Serum TGF-beta 1 could be used to assess therapeutic outcome and short-term prognosis of HCV-related chronic hepatitis.
No preview · Article · Oct 2008 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] 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.
No preview · Article · Sep 2008 · Clinical and experimental rheumatology
[Show abstract][Hide abstract] 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.
No preview · Article · Jun 2008 · Journal of Viral Hepatitis
[Show abstract][Hide abstract] ABSTRACT: One hundred and twenty-one patients with HCV-related chronic hepatitis and normal baseline thyroid function were studied. Forty-six patients received IFN alpha-2b, while 75 patients had Peg-IFN alpha-2b with ribavirin more recently. Thirty patients (ten belonging to the standard IFN group) were re-treated. The pre-treatment prevalence of thyroid antibodies was 3.3%. At the end of the first antiviral treatment, the prevalence of laboratory alterations (presence of antibodies and abnormal hormonal levels) of thyroid was assessed to be 20.7% (25 patients), being quite similar for standard-interferon- and pegylated-interferon-treated patients (P = 0.63). TSH level alteration was seen in eleven patients (9.1% of the overall population and 44% of the antibodies positive patients), of whom ten were females. The anti-microsomal, anti-thyroperoxidase and anti-thyroglobulin antibodies, in combined or isolated presence, were detected in all 25 patients. During the re-treatment we noticed worsening only of previous thyroid abnormalities. No patient changed the antiviral schedule after the emerging of thyroid alterations. All eleven patients remained thyroid dysfunctional at the end of the follow-up (ten with Hashimoto's thyroiditis and one with Graves disease), meanwhile the near totality of patients with presence of antibodies remained positive. Interestingly, eight out the 14 patients who showed mood disorders after antiviral therapy, belonged to the aforementioned cohort.
No preview · Article · Apr 2008 · International journal of immunopathology and pharmacology
[Show abstract][Hide abstract] ABSTRACT: To study the outcomes of patients with compensated hepatitis C virus-related cirrhosis.
Twenty-four grade A5 and 11 grade A6 of Child-Pugh classification cirrhotic patients with active virus replication, treated for a mean period of 31.3 +/- 5.1 mo with moderate doses of interferon-alpha and ribavirin, were compared to a cohort of 36 patients with similar characteristics, without antiviral treatment. Salivary caffeine concentration, a liver test of microsomal function, was determined at the starting and thrice in course of therapy after a mean period of 11 +/- 1.6 mo, meanwhile the resistive index of splenic artery at ultra sound Doppler, an indirect index of portal hypertension, was only measured at the beginning and the end of study.
Eight out of the 24 A5- (33.3%) and 5 out of the 11 A6- (45.45%) treated-cirrhotic patients showed a significant improvement in the total overnight salivary caffeine assessment. A reduction up to 20% of the resistive index of splenic artery was obtained in 3 out of the 8 A5- (37.5%) and in 2 out of the 5 A6- (40%) cirrhotic patients with an improved liver function, which showed a clear tendency to decrease at the end of therapy. The hepatitis C virus clearance was achieved in 3 out of the 24 (12.5%) A5- and 1 out of the 11 (0.091%) A6-patients after a median period of 8.5 mo combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but 3 patients (8.3%) had a worsening of the Child-Pugh score (P = 0.001).
A prolonged antiviral therapy with moderate dosages of interferon-alpha and ribavirin shows a trend to stable liver function or to ameliorate the residual liver function, the entity of portal hypertension and the compensation status at acceptable costs.
Full-text · Article · Oct 2007 · World Journal of Gastroenterology