[Show abstract][Hide abstract] ABSTRACT: Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.
PLoS ONE 08/2015; 10(8):e0135486. DOI:10.1371/journal.pone.0135486 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIM: To assess serum cartilage oligomeric matrix protein (COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma (HCC).
METHODS: A COMP enzyme-linked immunosorbent assay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range (IQR)] duration of 96.5 (102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.
RESULTS: COMP positivity (> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7% (14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age (P < 0.001), advanced fibrosis (P = 0.001) and necroinflammatory activity (P = 0.001), higher aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.02), γ-glutamyl transpeptidase (P = 0.003), alkaline phosphatase (P = 0.001), bilirubin (P < 0.05), international normalized ratio (P = 0.002) and alpha-fetoprotein levels (P < 0.02), and lower albumin (P < 0.001), and platelet count (P = 0.008). COMP levels [median (IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8 (7.9) U/L vs 9.8 (4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis (OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development (P = 0.007) and higher incidence of liver-related death (P < 0.001).
CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs
[Show abstract][Hide abstract] ABSTRACT: Monotherapy with standard or pegylated interferon (PegIFN) remains the first-line treatment for HCV infection in patients with thalassemia major (βTM), although its long-term impact is still unknown. We aimed to assess the efficacy of IFN-a2b/PegIFN-a2b (one or multiple treatment sessions) and the predictors for sustained virological response (SVR) in HCV-infected βTM patients.
Between 11/1992 and 12/2013 [median follow-up: 165.5 months (8-237)], 48 βTM HCV-infected patients [19 males, median age: 22 years (12-45)], received IFN-a2b (n=34) or PegIFN-a2b (n=14). Twenty-three patients (47.9%) had a previous splenectomy; 13/40 (32.5%) patients had Ishak stage >/=4 and 21/40 (52.5%) had siderosis grade 3-4. HCV-genotype was available in 36 patients (genotype 1: 47.2%, 2: 5.6%, 3: 25%, and 4: 22%). IL28B genotype was determined in 37 patients by means of in-house real-time PCR (CC: 27%, CT: 62.2%, TT: 10.8%).
Totally, 15/48 (31.3%) achieved SVR following the first treatment and 18/48 (37.5%) after multiple courses. Splenectomy (p=0.01) and fibrosis grade >/=4 (p<0.05) were negative predictors for SVR (first course), whereas splenectomy (p<0.05) and age >18 (p<0.02) for SVR after multiple courses. In HCV-genotype 1/4 (n=25), none of the patients with CT or TT IL28B genotype achieved SVR compared to 50% of the CC patients (p=0.004).
Interferon is an effective therapeutic option in HCV-infected βTM patients. IL28B genotype was a strong predictor for SVR, together with splenectomy, age and fibrosis.
Journal of gastrointestinal and liver diseases: JGLD 06/2015; 24(2):189. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brucellosis is a common zoonotic disease with worldwide distribution and protean clinical manifestations. Therefore, its prompt and timely diagnosis is still challenging. Among several complications of brucellosis, spontaneous bacterial peritonitis (SBP) in previously healthy participants is rarely recognised, although this condition can be fatal if misdiagnosed and untreated. We present a case of a 69-year-old previously healthy stockbreeder who suffered from back pain along with abdominal pain and distension because of ascites of 6-8 weeks duration. Cultures of ascitic fluid and peripheral blood specimens revealed Brucella spp as the causative agent of ascites and spondylodiscitis, which was then confirmed by MRI findings. After appropriate treatment for 4.5 months (streptomycin 1 g/day for 3 weeks intramuscularly, doxycycline 100 mg twice a day orally and rifampicin 900 mg/day orally), the patient fully recovered. Conclusively, in the appropriate epidemiological and clinical setting, the consideration of brucellosis in the differential diagnosis of SBP could be rational as well as life-saving.
2015 BMJ Publishing Group Ltd.
Case Reports 04/2015; 2015(apr22 1). DOI:10.1136/bcr-2015-209387
[Show abstract][Hide abstract] ABSTRACT: Background and Aims: Long-term ETV/TDF therapy represents the most common treatment option in CHB of any severity, but efficacy data have been mainly based on on-therapy virological remission rates. In this 9-center, large ongoing cohort study, we evaluated the survival in Caucasian CHB patients with or without cirrhosis who have been receiving ETV/TDF.
Methods: We included 1815 adult Caucasians with CHB with or without compensated cirrhosis and no HCC at baseline (mean age: 53±14 years, males: 71%, naive to antivirals: 60%, cirrhosis: 28%) who received ETV/TDF for ≥12 months. Liver transplantation free survival rates were estimated from Kaplan-Meier curves.
Results: In the total patient population, 1-, 2-, 3- and 5-year overall survival rates were 99.5%, 98.5%, 97.5% and 95% being significantly higher in non-cirrhotics (100%, 99%, 98.5% and 97%) than cirrhotics (98%, 96.5%, 95% and 92%, P<0.001). When only liver related deaths or LT were taken into account, 1-, 2-, 3- and 5-year survival rates were 99.7%, 99.4%, 99% and 97.5% being also significantly higher in non-cirrhotics (100%, 100%, 100% and 99%) than cirrhotics (99%, 98%, 97% and 95%, P<0.001). After excluding patients who developed HCC, 1-, 2-, 3- and 5-year overall survival rates were 99.5%, 99%, 98% and 96.5% remaining significantly higher in non-cirrhotics (100%, 99%, 99% and 98%) than cirrhotics (98%, 97.5%, 96.5% and 94%, P=0.001). In the 85 patients with HCC, the 1- and 3-year overall survival rates after HCC diagnosis were 76% and 56% without any difference between non-cirrhotics and cirrhotics (P=0.997). In multivariable Cox regression analysis, better overall survival was independently associated with absence of HCC [HR: 6.446 (95% CI: 3.647-11.394), P<0.001] and younger age [HR per year: 1.043 (1.019-1.069), P=0.001] but not with cirrhosis (P=0.085) or gender (P=0.438), while better liver related survival was associated only with absence of HCC [HR: 22.451 (9.891-50.780), P<0.001] and not with age (P=0.823), cirrhosis (P=0.123) or gender (P=0.970).
Conclusions: The survival of Caucasian CHB patients treated with ETV/TDF is excellent with >95% of cases surviving at 5 years and a significant proportion of deaths coming from liver unrelated causes. HCC development is a major factor affecting the overall mortality and the only factor affecting liver related mortality in such patients.
[Show abstract][Hide abstract] ABSTRACT: Background:
Although stroke is the fourth cause of death in Western societies, public stroke awareness remains suboptimal. The aim of this study was to estimate stroke risk perception and stroke awareness in Greece through a cross-sectional telephone survey.
A trained interview team conducted this cross-sectional telephone survey between February and April 2014 using an online structured questionnaire. Participants were selected using random digit dialing of landline and mobile telephone numbers with quota sampling weighted for geographical region based on the most recent General Population Census (2011).
Between February and April 2014, 723 individuals (418 women [58%], 47.4 ± 17.8 years) agreed to respond. Among all respondents, 642 (88.8%) were able to provide at least 1 stroke risk factor; 673 respondents (93.08%) were able to provide correctly at least 1 stroke symptom or sign. When asked what would they do in case of acute onset of stroke symptoms, 497 (68.7%) responded that they would either call the ambulance or visit the closest emergency department. Only 35.3%, 18.9%, 17.2%, 20.7%, and 15.0% of respondents with atrial fibrillation, arterial hypertension, dyslipidemia, diabetes mellitus, and current smoking, respectively, considered themselves as being in high risk for stroke.
Stroke risk perception in Greece is low despite moderate public stroke awareness.
Journal of Stroke and Cerebrovascular Diseases 02/2015; 24(2). DOI:10.1016/j.jstrokecerebrovasdis.2014.07.055 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background & AimsWe assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferonalfa-2a in routine clinical practice.Methods
Ninety-five HBeAg-negative patients receivedpeginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2,000 IU/mL at study week 96.ResultsTwenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥ 10% from baseline to week 24 was significantly associated with SR (81% [17/21] vs 37% [21/57]; Odds Ratio:7.286 [2.162–24.552], P=0.001). The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfill the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%).Conclusions
In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline>10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR.This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 11/2014; 35(5). DOI:10.1111/liv.12725 · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aims
The risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB) treated with entecavir (ETV) or tenofovir (TDF) is unclear. We evaluated the incidence and predictors of HCC and the accuracy of existing HCC risk scores in Caucasian CHB patients receiving ETV/TDF.
This large, multicenter, retrospective cohort study included 1666 adult Caucasian CHB patients under ETV/TDF for 39 months. CHB without cirrhosis, compensated and decompensated cirrhosis were present in 67%, 39% and 3% of patients. The predictability of baseline parameters and three risk scores (GAG-HCC, CU-HCC and REACH-B) developed in Asians was assessed.
The cumulative probability of HCC was 1.3%, 3.4% and 8.7% at year-1, year-3 and year-5 after ETV/TDF onset. Older age and lower platelets were strong independent HCC predictors in the total population and in the subgroups of cirrhotic and non-cirrhotic patients, while liver disease severity was an independent HCC predictor in the total population and the cirrhotics. GAG-HCC, CU-HCC and REACH-B risk scores were associated with HCC development only in the univariable but not in the multivariable analyses and offered poor to modest predictability.
HCC can still develop in Caucasian CHB patients treated with ETV/TDF. Besides the well known predictors of HCC, such as older age, male gender and more advanced liver disease, lower platelets represent an independent factor of higher HCC risk. The applicability and predictability of HCC risk scores developed in Asians are poor or modest in Caucasian CHB patients, for whom different risk scores are required.
Journal of Hepatology 09/2014; 62(2). DOI:10.1016/j.jhep.2014.08.045 · 11.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To estimate oxidative stress and antioxidant components during different stages of autoimmune liver diseases and assess their possible implication on disease progression.
We determined several markers of oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum, and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36 patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and age.
Both AC and AIH patients had increased levels of all lipid and protein oxidative injury products and significantly decreased whole blood glutathione levels compared to controls. AIH patients had significantly higher levels of aldehydes and glutathione peroxidase activity and significantly lower protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane levels increased and glutathione levels decreased gradually with progression from mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In addition, both cirrhotic AC and AIH patients had significantly higher protein carbonyls compared to non-cirrhotics.
We provide novel findings in support of a major contribution of oxidant/antioxidant imbalance in the progression of liver injury in AC and AIH.
Redox report: communications in free radical research 08/2014; 20(1). DOI:10.1179/1351000214Y.0000000101 · 1.52 Impact Factor