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Perrillo R.,Baylor University | Hou J.,Hepatology Unit | Papatheodoridis G.,Hippokration General Hospital of Athens | Manns M.,Hannover Medical School
Antiviral Therapy | Year: 2010

International treatment guidelines for hepatitis B emphasize alanine aminotransferase (ALT) and serum HBV DNA thresholds, but strict adherence to these markers might lead to missed opportunities in some patients with acquisition in early life. Clinical trials have used improvement in liver histology, rate of hepatitis B e antigen seroconversion and sustained HBV DNA suppression as primary end points. These are potentially short-term end points because HBV infection can not be eradicated and delayed relapses might occur. The closest end point to a clinical cure of disease is the loss of hepatitis B surface antigen (HBsAg). The ability of interferon to stimulate the immune response of the host might explain the higher rate of early HBsAg clearance when compared with nucleoside analogues. Early studies suggest that combination therapy with interferon and long-term treatment with nucleoside analogues might lead to an even higher rate of HBsAg seroconversion. Measuring HBsAg concentration during therapy might provide an early indication that a durable virological response, including HBsAg clearance, is likely to occur. Thus far, this has been best studied using interferon. The relationship of this phenomenon to viral genotype will be discussed. There is a need for more flexible on-treatment criteria for hepatitis B. HBsAg clearance remains the best therapeutic end point, but is not readily achievable with current treatments. Future treatment paradigms should take into account the duration as well as the extent of viraemia, place less reliance on the ALT level to indicate the extent of liver injury and consider the possibility that maintenance therapy can prevent liver disease complications. ©2010 International Medical Press. Source


Ekmektzoglou K.,National and Kapodistrian University of Athens | Samelis G.,Hippokration General Hospital of Athens | Karagiannis S.,Gastrointestinal and Liver Unit | Zografos G.,National and Kapodistrian University of Athens | Xanthos T.,National and Kapodistrian University of Athens
Acta Gastro-Enterologica Belgica | Year: 2012

Ulcerative colitis (UC), a chronic and relapsing idiopathic inflammatory disease of the colon, although not associated with an increased mortality compared to the general population, has a substantial morbidity leading to sizable health care costs, as it carries an increased risk for development of colorectal cancer (CRC). The pathophysiology behind this carcinogenic pathway is multifactorial. This review summarizes the major pathogenetic steps from which the inflamed colonic epithelium is transformed to a dysplastic and/or cancerous one. The role of the inflammatory and immune system, the oxidative stress generated as well as the genomic stability observed in UC-associated CRC is presented so as to provide a more spherical view of the tumorigenic process and, if possible, offer new diagnostic approaches for the early detection of CRC. Source


Papatheodoridis G.V.,National and Kapodistrian University of Athens | Manolakopoulos S.,National and Kapodistrian University of Athens | Touloumi G.,National and Kapodistrian University of Athens | Nikolopoulou G.,Viral Hepatitis Committee | And 13 more authors.
Journal of Viral Hepatitis | Year: 2015

Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients treated with lamivudine. Whether HCC rates are comparable in patients treated with the current first-line antivirals remains uncertain. We estimated the incidence and evaluated predictors of HCC in a large nationwide prospective cohort (HepNet.Greece) of HBeAg-negative CHB patients treated with entecavir. HBeAg-negative CHB patients from the same cohort who were initially treated with lamivudine were used as controls. We included 321 patients treated with entecavir for a median of 40 months and 818 patients treated initially with lamivudine for a median of 60 months. In the entecavir group, HCC developed in 4 of 321 (1.2%) patients at a median of 1.5 (range: 1.0-4.5) years, while the cumulative HCC incidence was significantly higher in cirrhotics than noncirrhotics (1, 3, 5 years: 0%, 3%, 9% vs 1%, 1%, 1%; P = 0.024) and in older patients (P = 0.026). Entecavir compared with lamivudine group patients had lower HCC incidence (1, 3, 5 years: 0.3%, 1.2%, 2.8% vs 0.7%, 3.8%, 5.6%; P = 0.024). However, in multivariable Cox regression analysis, the HCC risk was independently associated with older age (P < 0.001), male gender (P = 0.011) and cirrhosis (P = 0.025), but not with the initial agent. In conclusion, our large nationwide study indicates that the HCC risk remains increased in entecavir-treated HBeAg-negative CHB patients with cirrhosis, particularly of older age, at least for the first 5 years. The HCC risk does not seem to be significantly reduced with entecavir compared with antiviral therapy starting with lamivudine. © 2014 John Wiley & Sons Ltd. Source


Papatheodoridis G.V.,National and Kapodistrian University of Athens | Manolakopoulos S.,National and Kapodistrian University of Athens | Touloumi G.,National and Kapodistrian University of Athens | Vourli G.,National and Kapodistrian University of Athens | And 7 more authors.
Gut | Year: 2011

Objective: To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy. Design: Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective-prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months. Setting: A nationwide network of liver centres. Patients: 818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity. Interventions: All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy. Main outcome measures: Development of HCC. Results: During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50-60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission. Conclusions: Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC. Source


Lobo M.D.,Queen Mary, University of London | Sobotka P.A.,ROX Medical | Sobotka P.A.,Ohio State University | Stanton A.,Royal College of Surgeons in Ireland | And 16 more authors.
The Lancet | Year: 2015

Background: Hypertension contributes to cardiovascular morbidity and mortality. We assessed the safety and efficacy of a central iliac arteriovenous anastomosis to alter the mechanical arterial properties and reduce blood pressure in patients with uncontrolled hypertension. Methods: We enrolled patients in this open-label, multicentre, prospective, randomised, controlled trial between October, 2012, and April, 2014. Eligible patients had baseline office systolic blood pressure of 140 mm Hg or higher and average daytime ambulatory blood pressure of 135 mm Hg or higher systolic and 85 mm Hg or higher diastolic despite antihypertensive treatment. Patients were randomly allocated in a 1:1 ratio to undergo implantation of an arteriovenous coupler device plus current pharmaceutical treatment or to maintain current treatment alone (control). The primary endpoint was mean change from baseline in office and 24 h ambulatory systolic blood pressure at 6 months. Analysis was by modified intention to treat (all patients remaining in follow-up at 6 months). This trial is registered with ClinicalTrials.gov, number NCT01642498. Findings: 83 (43%) of 195 patients screened were assigned arteriovenous coupler therapy (n=44) or normal care (n=39). Mean office systolic blood pressure reduced by 26.9 (SD 23.9) mm Hg in the arteriovenous coupler group (p<0.0001) and by 3.7 (21.2) mm Hg in the control group (p=0.31). Mean systolic 24 h ambulatory blood pressure reduced by 13.5 (18.8) mm Hg (p<0.0001) in arteriovenous coupler recipients and by 0.5 (15.8) mm Hg (p=0.86) in controls. Implantation of the arteriovenous coupler was associated with late ipsilateral venous stenosis in 12 (29%) of 42 patients and was treatable with venoplasty or stenting. Interpretation: Arteriovenous anastomosis was associated with significantly reduced blood pressure and hypertensive complications. This approach might be a useful adjunctive therapy for patients with uncontrolled hypertension. Source

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