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1.
Emerg Infect Dis ; 29(7): 1479-1481, 2023 07.
Article in English | MEDLINE | ID: mdl-37253276

ABSTRACT

We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against nucleocapsid. In the next 2 years, titers increased despite few COVID-19 symptoms. On multivariate analysis, allergic rhinitis was associated with reduced risk for symptomatic COVID-19.


Subject(s)
Blood Donors , COVID-19 , Humans , SARS-CoV-2 , Seroepidemiologic Studies , COVID-19/epidemiology , Communicable Disease Control , Italy/epidemiology , Antibodies, Viral
2.
Hepatology ; 68(3): 1010-1024, 2018 09.
Article in English | MEDLINE | ID: mdl-29604220

ABSTRACT

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA-treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin-2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C-reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo-Doppler work-up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = -0.412, P = 0.037 and r = -0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3-month follow-up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044-1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080-2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395-16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127-13.203; P = 0.032) were independent predictors of de novo HCC. CONCLUSION: Our study indicates that DAA-mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo-angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000-000).


Subject(s)
Angiopoietin-2/blood , Antiviral Agents/adverse effects , Carcinoma, Hepatocellular/chemically induced , Hepatitis C/drug therapy , Liver Neoplasms/chemically induced , Neoplasm Recurrence, Local/chemically induced , Aged , Carcinoma, Hepatocellular/blood , Female , Hepatitis C/complications , Humans , Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Cirrhosis/virology , Liver Neoplasms/blood , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neovascularization, Pathologic , Prospective Studies , Tumor Microenvironment , Vascular Endothelial Growth Factor A/blood
3.
J Hepatol ; 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28882581

ABSTRACT

BACKGROUND & AIMS: Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. METHODS: Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV-, from a large de-identified insurance database from the USA. MEASUREMENTS: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17ß-estradiol were measured. RESULTS: Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771-26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090-0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV-, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130-2.794), premature birth (OR 1.34; 95% CI 1.060-1.690), gestational diabetes (OR 1.24; 95% CI 1.020-1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935-1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622-0.913). CONCLUSIONS: Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. LAY SUMMARY: Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

5.
Gastroenterology ; 143(5): 1253-1260.e4, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22819864

ABSTRACT

BACKGROUND & AIMS: We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. METHODS: In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child-Pugh classes B7-C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n = 34) or no treatment (controls, n = 36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was prevention of PVT. Radiologists and hepatologists that assessed outcomes were blinded to group assignments. Analysis was by intention to treat. RESULTS: At 48 weeks, none of the patients in the enoxaparin group had developed PVT, compared with 6 of 36 (16.6%) controls (P = .025). At 96 weeks, no patient developed PVT in the enoxaparin group, compared with 10 of 36 (27.7%) controls (P = .001). At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT (P = .048). The actuarial probability of PVT was lower in the enoxaparin group (P = .006). Liver decompensation was less frequent among patients given enoxaparin (11.7%) than controls (59.4%) (P < .0001); overall values were 38.2% vs 83.0%, respectively (P < .0001). The actuarial probability of liver decompensation was lower in the enoxaparin group (P < .0001). Eight patients in the enoxaparin group and 13 controls died. The actuarial probability of survival was higher in the enoxaparin group (P = .020). No relevant side effects or hemorrhagic events were reported. CONCLUSIONS: In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child-Pugh score of 7-10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival.


Subject(s)
Anticoagulants/therapeutic use , DNA, Bacterial/blood , Enoxaparin/therapeutic use , Liver Cirrhosis/complications , Liver Failure/prevention & control , Renal Veins , Thrombosis/prevention & control , Anticoagulants/adverse effects , Bacterial Infections/blood , Bacterial Translocation , Biomarkers/blood , Enoxaparin/adverse effects , Fatty Acid-Binding Proteins/blood , Female , Humans , Interleukin-6/blood , Kaplan-Meier Estimate , Lipopolysaccharide Receptors/blood , Liver Failure/etiology , Male , Middle Aged , Proportional Hazards Models , Statistics, Nonparametric , Thrombosis/complications
6.
Gastroenterology ; 140(3): 818-29, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21167831

ABSTRACT

BACKGROUND & AIMS: Chronic hepatitis C (CHC) and liver fibrosis progress more rapidly in men and menopausal women than in women of reproductive age. We investigated the associations among menopause, sustained virologic response (SVR), and liver damage in patients with CHC. METHODS: We performed a prospective study of 1000 consecutive, treatment-naïve patients 18 years of age and older with compensated liver disease from CHC. Liver biopsy samples were analyzed (for fibrosis, inflammation, and steatosis) before patients received standard antiviral therapy. From women (n = 442), we collected data on the presence, type, and timing of menopause; associated hormone and metabolic features; serum levels of interleukin-6; and hepatic tumor necrosis factor (TNF)-α. RESULTS: Postmenopausal women achieved SVRs less frequently than women of reproductive age (46.0% vs 67.5%; P < .0001) but as frequently as men (51.1%; P = .283). By multivariate regression analysis, independent significant predictors for women to not achieve an SVR were early menopause (odds ratio [OR], 8.055; 95% confidence interval [CI], 1.834-25.350), levels of γ-glutamyl transpeptidase (OR, 2.165; 95% CI, 1.364-3.436), infection with hepatitis C virus genotype 1 or 4 (OR, 3.861; 95% CI, 2.433-6.134), and cholesterol levels (OR, 0.985; 95% CI, 0.971-0.998). Early menopause was the only independent factor that predicted lack of an SVR among women with genotype 1 hepatitis C virus infection (OR, 3.933; 95% CI, 1.274-12.142). Baseline levels of liver inflammation, fibrosis, steatosis, serum interleukin-6 (P = .04), and hepatic TNF-α (P = .007) were significantly higher among postmenopausal women than women of reproductive age. CONCLUSIONS: Among women with CHC, early menopause was associated with a low likelihood of SVR, probably because of inflammatory factors that change at menopause.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Menopause, Premature , Adult , Age Factors , Biomarkers/metabolism , Biopsy , Female , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/immunology , Humans , Immunohistochemistry , Inflammation Mediators/metabolism , Interleukin-6/blood , Italy , Liver Cirrhosis/diagnosis , Liver Cirrhosis/virology , Logistic Models , Male , Menopause, Premature/immunology , Middle Aged , Odds Ratio , Prospective Studies , RNA, Viral/blood , Risk Assessment , Risk Factors , Severity of Illness Index , Sex Factors , Time Factors , Treatment Failure , Tumor Necrosis Factor-alpha/metabolism , Viral Load
7.
Blood Adv ; 5(3): 662-673, 2021 02 09.
Article in English | MEDLINE | ID: mdl-33560382

ABSTRACT

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.


Subject(s)
Angiopoietin-2/blood , COVID-19/pathology , Antiviral Agents/therapeutic use , Area Under Curve , Biomarkers/blood , COVID-19/mortality , COVID-19/virology , Hospital Mortality , Hospitalization , Humans , Interleukin-6/blood , Proportional Hazards Models , ROC Curve , Risk Factors , SARS-CoV-2/isolation & purification , Survival Rate , COVID-19 Drug Treatment
8.
Ann Intern Med ; 146(8): 556-63, 2007 Apr 17.
Article in English | MEDLINE | ID: mdl-17438314

ABSTRACT

BACKGROUND: Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. OBJECTIVE: To determine whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two Italian hospitals between September 2003 and April 2006. PATIENTS: 300 patients with dyspepsia or peptic ulcers. MEASUREMENTS: (13)C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance. INTERVENTION: A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). RESULTS: The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P = 0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per-protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects. LIMITATIONS: Follow-up was incomplete in 4.6% and 2.7% patients in the sequential therapy and standard therapy groups, respectively. The results may not be generalizable to other countries. Sequential therapy may be more effective because it includes 1 additional antibiotic (tinidazole) that is not contained in standard therapy. CONCLUSIONS: Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains. Side effects are similar with both treatment regimens and are rarely severe enough to cause discontinuation of therapy. ClinicalTrials.gov registration number: NCT00403364.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/administration & dosage , Dyspepsia/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori , Peptic Ulcer/drug therapy , Adult , Aged , Anti-Bacterial Agents/adverse effects , Anti-Ulcer Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Drug Resistance, Bacterial , Drug Therapy, Combination , Dyspepsia/microbiology , Female , Humans , Male , Middle Aged , Peptic Ulcer/microbiology , Prospective Studies
9.
PLoS One ; 12(10): e0185728, 2017.
Article in English | MEDLINE | ID: mdl-28977040

ABSTRACT

BACKGROUND: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. AIM: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. METHODS: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. RESULTS: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications. CONCLUSIONS: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Liver Diseases/drug therapy , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Drug Therapy, Combination , Female , Hepatitis C/genetics , Hepatitis C/pathology , Humans , Incidence , Liver Diseases/genetics , Liver Diseases/pathology , Male , Middle Aged , Prospective Studies
10.
Ann Ital Med Int ; 20(1): 23-7, 2005.
Article in Italian | MEDLINE | ID: mdl-15859391

ABSTRACT

Helicobacter pylori (H. pylori) infection may be diagnosed by means of invasive techniques requiring endoscopy and biopsy (histological examination, rapid urease test, culture, polymerase chain reaction) and by non-invasive techniques (urea breath test, detection of specific antibodies in the serum or urine, detection of the H. pylori antigen in a stool specimen). Some non-invasive tests detect active infection e.g. the urea breath test and the stool antigen test and are called active tests. Other non-invasive tests are markers of exposure to H. pylori (e.g. serology or urine) but do not indicate whether active infection is ongoing and are called passive tests. Non-invasive tests and treatment strategies are widely recommended in primary care settings and the choice of the appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness. The available non-invasive tests are reviewed in this article.


Subject(s)
Helicobacter Infections/diagnosis , Helicobacter pylori , Humans
11.
Postgrad Med ; 117(6): 17-22, 46, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16001764

ABSTRACT

As evidence about the relationship between Helicobacter pylori infection and peptic ulcers accumulates, accurate testing and treatment are becoming increasingly important. However, big questions remain about the best strategies for detecting and managing this infection. In this article, the authors discuss the association between H pylori and peptic ulcer disease, the available tests for detecting the infection, and the latest treatment strategies for effective eradication.


Subject(s)
Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter pylori , Peptic Ulcer/microbiology , Age Factors , Age of Onset , Algorithms , Antigens, Bacterial/analysis , Breath Tests , Drug Therapy, Combination , Duodenal Ulcer/microbiology , Feces/microbiology , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Humans , Prevalence , Proton Pump Inhibitors , Stomach Neoplasms/microbiology , Stomach Ulcer/microbiology
12.
J Clin Virol ; 62: 89-91, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25542480

ABSTRACT

HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source.


Subject(s)
Hepatitis B Vaccines/adverse effects , Hepatitis B virus , Hepatitis B/virology , Amino Acid Sequence , Genotype , Hepatitis B/drug therapy , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B Surface Antigens/chemistry , Hepatitis B Surface Antigens/genetics , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/genetics , Hepatitis B Vaccines/immunology , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Sequence Alignment , Vaccination/adverse effects
13.
Article in English | MEDLINE | ID: mdl-25083900

ABSTRACT

Although not a classical target for estrogens, the liver is a target for their action and is sensitive to their deprivation. The occurrence of menopause is accompanied by a chain of events depending on the progressive estrogen deprivation that eventually leads to a shift from a low inflammatory to a high inflammatory state. This has a series of well-known consequences in many different organs and tissues (bone, heart, brain, body fat etc.) among which the liver is particularly interesting. The consequences are extremely evident in HCV-positive women in whom HCV infection and menopause cooperate to induce higher necro-inflammatory features, increased hepatic steatosis and eventually faster progression of fibrosis. In addition, menopause is the strongest negative factor for sustained viral response (SVR) in HCV-positive females, especially HCV genotype 1 (in whom menopause was the only independent factor for failure of antiviral therapy). This suggests that HCV-positive women should be treated early during fertile age to obtain maximal response to antiviral therapy.


Subject(s)
Hepatitis C, Chronic/physiopathology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Drug Resistance, Viral , Female , Hepatitis C, Chronic/drug therapy , Humans , Male , Menopause , Platelet Count , Sex Characteristics
15.
World J Gastroenterol ; 20(44): 16726-33, 2014 Nov 28.
Article in English | MEDLINE | ID: mdl-25469044

ABSTRACT

AIM: To investigate the safety/efficacy of Boceprevir-based triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEG-IFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used. RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (P = 0.250), in 44% F0-F2 vs 54% F3-F4 (P = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only (6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Menopause , Proline/analogs & derivatives , Antiviral Agents/adverse effects , Biomarkers/blood , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Hepacivirus/pathogenicity , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Italy , Logistic Models , Middle Aged , Multivariate Analysis , Odds Ratio , Polyethylene Glycols/therapeutic use , Proline/adverse effects , Proline/therapeutic use , RNA, Viral/blood , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Time Factors , Treatment Outcome , Viral Load
16.
PLoS One ; 7(9): e44624, 2012.
Article in English | MEDLINE | ID: mdl-22970270

ABSTRACT

INTRODUCTION: Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men. MATERIALS AND METHODS: A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis. RESULTS: Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001) or premenopausal (P = 0.042) group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052). Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048) and early menopausal (P = 0.004) but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001) and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001). In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001). CONCLUSIONS: The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the inflammatory process leading to fibrosis.


Subject(s)
Hepatitis C/physiopathology , Infertility, Female/physiopathology , Liver Cirrhosis/physiopathology , Case-Control Studies , Female , Humans , Male , Retrospective Studies , Severity of Illness Index
17.
Am J Gastroenterol ; 99(10): 1910-5, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15447749

ABSTRACT

OBJECTIVE: Atrophic gastritis is a precancerous condition that is commonly caused by chronic Helicobacter pylori (H. pylori) infection. This blinded, controlled study was designed to determine if serum gastrin and pepsinogens were reliable markers of atrophy in asymptomatic patients. METHODS: One hundred and forty-seven asymptomatic patients underwent endoscopy with multiple gastric biopsies obtained for histology, culture, and rapid urease test. Fasting serum gastrin (total and G-17) and serum pepsinogens (I-II) were determined by standard immunoassays. Gastric atrophy was histologically assessed in accordance with internationally accepted criteria; three main patterns of gastritis were distinguished: (a) nonatrophic gastritis, (b) atrophic antrum-restricted and antrum-predominant gastritis, and (c) corpus-restricted gastritis. Receiving operating characteristic (ROC) analysis was used to determine the best cut-off for each serum test in nonatrophic gastritis versus antrum-restricted/antrum-predominant atrophic gastritis. RESULTS: No significant differences in serum gastrin and pepsinogens I-II were detected in nonatrophic gastritis versus patients with antrum-restricted/antrum-predominant atrophic gastritis. The positive likelihood ratios for an abnormal serum test to detect antrum-restricted/antrum-predominant atrophy in the gastric body were total serum gastrin 2.13 (95% CI 0.99, 4.6), gastrin-17: 1.55 (95% CI 0.75, 36.17), pepsinogen I: 2.74 (1.4, 5.4), pepsinogen II: 1.74 (1.27, 2.39), and the ratio of pepsinogen I and II: 1.8 (1.2-2.8). Negative likelihood ratios ranged from 0.20 to 0.65. CONCLUSION: In an asymptomatic population, serum gastrin (total and G-17) and pepsinogens I-II (and their ratio) do not discriminate nonatrophic versus antrum-restricted/predominant atrophic gastritis.


Subject(s)
Helicobacter Infections/blood , Helicobacter pylori , Stomach/pathology , Atrophy/blood , Biomarkers/blood , Female , Gastrins/blood , Humans , Male , Middle Aged , Multivariate Analysis , Pepsinogen A/blood , Reproducibility of Results , Single-Blind Method
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