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Aim: To investigate the frequency and timing of post-partum chronic hepatitis B virus (HBV) reactivation and identify its pre-partum predictors., Methods: Forty-one hepatitis B e antigen (HBeAg)-negative chronic HBV infected pregnant women were prospectively evaluated between the 28th and the 32nd week of gestation. Subjects were re-evaluated at 3-mo intervals during the first post-partum year and every 6 mo during the following years. HBV DNA was determined using real-time reverse transcription polymerase chain reaction (Cobas TaqMan HBV Test) with a lower detection limit of 8 IU/mL. Post-partum reactivation (PPR) was defined as abnormal alanine aminotransaminase (ALT) levels and HBV DNA above 2000 IU/mL., Results: Fourteen out of 41 women (34.1%) had pre-partum HBV DNA levels>2000 IU/mL, 18 (43.9%) had levels<2000 IU/mL and 9 (21.9%) had undetectable levels. Fourteen women were lost to follow-up (failure to return). PPR occurred in 8 of the 27 (29.6%) women evaluated, all within the first 6 mo after delivery (5 at month 3; 3 at month 6). Five of the 6 (83.3%) women with pre-partum HBV DNA>10000 IU/mL exhibited PPR compared with 3 of the 21 (14.3%) women with HBV DNA<10000 IU/mL (two with HBV DNA>2000 and the third with HBV DNA of 1850 IU/mL), P=0.004. An HBV DNA level≥10000 IU/mL independently predicted post-partum HBV infection reactivation (OR=57.02, P=0.033). Mean pre-partum ALT levels presented a non-significant increase in PPR cases (47.3 IU/L vs 22.2 IU/L, respectively, P=0.094)., Conclusion: In the present study, PPR occurred in approximately 30% of HBeAg-negative pregnant women; all events were observed during the first semester after delivery. Pre-partum HBV DNA level>10000 IU/mL predicted PPR.

Chronic hepatitis C and B are well-recognized and potentially preventable risk factors for hepatocellular carcinoma (HCC) development. Clinical and epidemiological studies suggest that therapy with interferon-α may reduce the overall risk of HCC development in patients with chronic hepatitis C, who achieve sustained virological response, but even in those who fail to eradicate the infection. In chronic hepatitis B, interferon therapy reduces the risk of HCC development in HBeAg-positive and cirrhotic patients who achieve persistent suppression of viral replication, while in HBeAg-negative patients the beneficial effect of interferon-α is not definitively confirmed. The preventive role of interferon-α after potentially curative treatment for HCC in both chronic hepatitis B and C is uncertain due to methodological flaws of the existing studies and prospective randomized controlled trials with pegylated interferon-α are needed to clarify this issue., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Chronic hepatitis C affects 2.2 - 3% of the world population (130 million - 170 million). Pegylated IFN-α in combination with ribavirin, the currently approved therapy, leads to viral eradication in about 50% of treated patients, nevertheless it is associated with not negligible adverse events. Continuous efforts are being applied to improve the efficacy by means of new interferon molecules. Consensus IFN-α is currently available for use, while albumin-interferon, IFN-λ and IFN-ω are under investigation. Research is focussed on the directly acting antivirals, such as telaprevir and boceprevir, which are anticipated to enter the drug market during the next few years., Areas Covered: This paper reviews the classification of interferons, mechanism of action, pegylated IFN-α molecules and their differences, current chronic hepatitis C treatment regimen and new drugs for HCV treatment., Expert Opinion: Pegylated IFN-α will remain the basis of anti-HCV therapy during the next decade, since new IFN formulation are not proven to be superior or are in early stages of development and directly acting antivirals show limited antiviral activity as monotherapy.

Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. In this study the spontaneous preterm birth rates in a group of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected pregnant women without known risk factors for preterm delivery as well as the role of maternal laboratory data and hepatitis B surface antigen/HBV deoxyribonucleic acid (HBV-DNA) in cord blood in respect to preterm labour were evaluated. 138 consecutive HBeAg-negative chronic HBV-infected pregnant women were evaluated during the perinatal period. Serum HBV-DNA was determined by using the Cobas Amplicor HBV Test in both maternal and cord blood samples. 102 women were finally evaluated (36 were excluded) and 15 of them (14.7%) had spontaneous preterm birth. A significant association between spontaneous preterm birth and HBV-DNA in cord blood was observed (p = 0.007). HBV-DNA positivity in cord blood was significantly associated with maternal HBV-DNA levels (p = 0.002). The relative risk of HBV-DNA in cord blood was 6.43 times higher among women with serum HBV-DNA ≥10,000 copies/ml and lymphocyte count <1,500 compared to those with all the other combinations of both parameters (p = 0.001). In conclusion, the presence of HBV-DNA in cord blood is significantly associated with spontaneous preterm birth in chronic HBV-infected pregnant women. Women with HBV-DNA ≥10,000 copies/ml and lymphocyte count <1,500 during the perinatal period have a higher probability of HBV-DNA in their cord blood., (Copyright © 2011 S. Karger AG, Basel.)

Background: Cirrhosis developing during chronic infection with the hepatitis C virus (HCV) poses a risk of anticipated liver-related death, therefore representing a dominant indication to anti-HCV therapy., Objective: This review highlights the efficacy and safety of treatment of HCV infection in cirrhotic patients with respect to the clinical stage of the disease., Methods: The PubMed, MEDLINE, EMBASE, and Cochrane databases, as well as the conference proceedings from the annual meetings of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver, were searched for articles published in English from January 1990 through May 2010, fulfilling the following criteria: (1) randomized, prospective observational, retrospective, or meta-analysis; (2) involving adult patients with chronic HCV infection; and (3) data (fibrosis stage, treatment regimen, efficacy, safety) available for cirrhotics. Reviews were excluded. Search terms included chronic hepatitis C, fibrosis, cirrhosis, interferon alfa, ribavirin, hepatocellular carcinoma, and liver decompensation., Results: Forty-five studies were identified. The rates of sustained virologic response to pegylated interferon in combination with ribavirin ranged from 10% to 44% for HCV genotypes 1/4 to 33% to 72% for genotypes 2/3 in compensated cirrhosis, while falling to 0% to 16% and 44% to 57%, respectively, in the decompensated stage, compared with 29% to 55% for genotypes 1/4 and 70% to 80% for genotypes 2/3 in noncirrhotic patients (compensated cirrhosis vs no cirrhosis: P < 0.001 for genotypes 1/4 and P = 0.002 for genotypes 2/3; decompensated cirrhosis vs no cirrhosis: P < 0.001 for all genotypes). HCV clearance was associated with a reduced risk of liver decompensation, hepatocellular carcinoma development, liver-related mortality, and hepatitis recurrence after liver transplantation. Treatment during compensated cirrhosis proved to be most cost-effective versus treatment after decompensation or a no-treatment strategy. Headache (54%), irritability (38%), fatigue (34%), and nausea (30%) were the most common adverse events in compensated patients, while anorexia (100%), fatigue (59%), neutropenia (53%), and thrombocytopenia (50%) were most common in decompensated patients., Conclusions: Anti-HCV treatment in cirrhotic patients was less effective than in noncirrhotic patients. Viral eradication reduced the risk of liver complications and improved survival in noncirrhotics. Based on effectiveness and tolerability data, therapy has a significant effect in patients with compensated cirrhosis, while decompensated patients need to weigh the risks versus benefits of treatment., (Copyright © 2010 Elsevier HS Journals, Inc. Published by EM Inc USA.. All rights reserved.)

Objective: To determine whether chronic hepatitis B virus (HBV) infection, as evidenced by serum levels of HBsAg and HBV DNA, is a risk factor for spontaneous preterm birth (SPB)., Method: The prevalence of HBV infection and the SPB rate were prospectively investigated among 1826 pregnant women, 30.89% Albanian and the remainder of other European origins., Results: Overall, 70 (3.8%) of the women were chronically infected with HBV. HBsAg status was strongly linked to SPB, which incurred to 5 (7.3%) of 64 women with circulating HBsAg compared with 28 (1.6%) of 1703 without current HBV infection (odds ratio, 5.2; P=0.007). SPB, however, was linked neither to HBsAg levels, nor to HBV DNA levels, nor to the presence or absence of viremia., Conclusion: Pregnant women were found to be at higher risk for SPB if they had circulating HBsAg, and the risk did not seem to be influenced by the levels of HBsAg or HBV DNA., (Copyright 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.

Background and Aims: Thyroid dysfunction (TD) represents an extrahepatic manifestation of chronic hepatitis C (CHC). Moreover, the currently approved treatment of CHC is often associated with TD. However, it remains debatable if TD is mainly virus- or treatment-related. The aim of this study was to assess the incidence and features of TD, and to identify its predictors in treated and untreated CHC patients., Methods: Ninety-four patients with CHC and normal thyroid function were evaluated long-term for TD: 33 were untreated (control group) and 61 were treated with pegylated interferon alpha (PEG-IFN-alpha) plus ribavirin (treatment group). Mean follow up was 80.1 and 39.4 months, respectively., Results: All patients in the control group remained euthyroid, while 13 treated patients (21.3%) developed TD (P < 0.001). Eleven of these were diagnosed with hypothyroidism and two with hyperthyroidism, which then converted to hypothyroidism. In the majority of cases (9/13, 69.2%) TD did not reverse after treatment discontinuation and required hormone replacement therapy. Pretreatment virological parameters did not predict TD, according to multiple logistic regression analysis. TD was not associated with total dose of PEG-IFN-alpha or ribavirin, viral kinetics or with virological outcome, but it was linked to development of other therapy-related autoimmune disorders (odds ratio, 8.29)., Conclusion: Antiviral therapy of CHC possibly induces de novo or exacerbates pre-existing silent TD. TD does not seem to correlate with any pretreatment virological parameter; it is probably not related to dose or treatment duration, nor linked to viral kinetics or virological outcome. The role of chronic hepatitis C per se in TD remains to be determined.

Objectives: We assessed the comparative prognostic role of left ventricular hypertrophy (LVH) and chronic kidney disease (CKD) for major cardiovascular events in a prospective observational study in Greek essential hypertensive patients., Methods: We followed up 1652 hypertensive patients (mean age 54.3 years, 696 male patients, office blood pressure 147/93 mmHg) free of cardiovascular disease for a mean period of 6 years. CKD and echocardiographically detected LVH were evaluated at baseline along with five major traditional risk factors [age > 65 years, sex, current smoking, diabetes mellitus and dyslipidemia (low density lipoprotein > 160 mg/dl)]. End points of interest were the incidence of coronary artery disease, stroke, all-cause mortality and their composite., Results: At the end of follow-up, coronary artery disease was the most prevalent (5.2%), followed by stroke (5%) and total mortality (3.1%). The presence of both LVH and CKD is associated with a 2.5-fold increase in coronary artery disease (P = 0.034), four-fold in stroke (P = 0.002) and 3.2-fold in the composite (P < 0.001), whereas the presence of LVH alone was associated with a 2.5-fold higher risk for stroke (P = 0.009) and 1.7-fold for the composite (P = 0.018). By multivariate Cox regression analysis, LVH (hazard ratio = 1.53, P = 0.036) and CKD (hazard ratio = 1.66, P = 0.039) turned out to be independent prognosticators of the composite end point, whereas age more than 65 years (hazard ratio = 4.59, P < 0.001) and the presence of LVH (hazard ratio = 2.01, P = 0.043) were the only predictors of stroke., Conclusions: In hypertensive patients free of cardiovascular disease, CKD and LVH are both independent prognosticators of the composite end point of all-cause death and cardiovascular morbidity, whereas LVH but not CKD is a major predictor for stroke.

Epidemiological data on the prevalence of serological markers of hepatitis B virus (HBV) infection in pregnant women in Greece are limited. We evaluated the prevalence of HBV serological markers in a multinational population of pregnant women in Athens, Greece. The overall prevalence of hepatitis B surface antigen (HbsAg) was 4.1% with the highest rates among Albanian immigrants (12%). Relatively low vaccination-induced protection rates (32.5%) were observed, a finding suggesting that surveillance and immunisation programmes targeted at pregnant women are necessary.

Aim: To evaluate the impact of hepatitis B core antibody (anti-HBc) seropositivity in sustained virological response (SVR) rates in treatment-naïve, chronic hepatitis C (CHC) patients with high pretreatment viral load (>800000 IU/mL)., Methods: 185 consecutive CHC patients (14.4% cirrhotics, 70.2% prior intravenous drug users) treated with pegylated interferon-a2b plus ribavirin, for 24 or 48 weeks based on viral genotype, were retrospectively analyzed. SVR was confirmed by undetectable serum HCV-RNA six months after the end of treatment schedule., Results: Thirty percent of CHC/HBsAg-negative patients were anti-HBc-positive. Anti-HBc positivity was more prevalent in cirrhotic, compared to noncirrhotic patients (76.9% versus 19.5%, P < .05). Serum HBV-DNA was detected in the minority of anti-HBc-positive patients (1.97%). Overall, 62.1% of patients exhibited SVR, while 28.6% did not; 71.4% of non-SVRs were infected with genotype 1. In the univariate analysis, the anti-HBc positivity was negatively associated with treatment outcome (P = .065). In the multivariate model, only the advanced stage of liver disease (P = .015) and genotype-1 HCV infection (P = .003), but not anti-HBc-status (P = .726), proved to be independent predictors of non-SVR., Conclusion: Serum anti-HBc positivity does not affect the SVR rates in treatment-naïve CHC patients with high pretreatment viral load, receiving the currently approved combination treatment.

Objectives: To investigate early viral kinetics, sustained virological response (SVR) rates and their predictors, in treatment-naïve, genotype-4-infected, chronic hepatitis C (CHC) patients treated with PEG-IFNalpha2b plus ribavirin., Patients and Methods: In total, 58 patients were retrospectively analyzed. Early virological response (EVR) was defined as undetectable HCV-RNA (<50 IU/ml) at week 12 (complete, cEVR) or at least a 2 log decrease in HCV-RNA levels (partial, pEVR)., Results: Thirty-one patients exhibited SVR (53.4%), 17 (29.3%) were non-responders and 10 (17.2%) relapsed. Thirty-seven patients (63.8%) exhibited EVR. The positive predictive values of EVR, cEVR and pEVR for the SVR achievement were 83.87, 54.83, and 29.03%, whereas their negative predictive values were 59.25, 77.77, and 81.48%, respectively. Both cEVR (OR 0.040, p = 0.042) and EVR (OR 0.016, p = 0.006) independently predicted SVR. Baseline viral load (p < 0.001), age (p = 0.035) and stage of liver disease (p = 0.04) were significantly related to the EVR achievement, whereas only baseline viral load (p = 0.003) and ethnicity (p = 0.025) predicted cEVR., Conclusions: Partial or complete EVR represent independent predictors of SVR in genotype-4-infected CHC patients, regardless of their baseline parameters. The absence of pEVR, rather than the absence of cEVR, should be used as an early indication for discontinuation of treatment in these patients., (Copyright (c) 2009 S. Karger AG, Basel.)

Primary (AL) amyloidosis is the most common form of systemic amyloidosis seen in current clinical practice. The symptoms of the disease are usually vague, special features are seen in fewer than one fifth of patients, and the combination of organs and systems involved provides a clue for the diagnosis. We describe a patient in whom asymptomatic hepatomegaly, cardiomegaly, hyperlipidaemia and elevated serum alkaline phosphatase level were found during routine examination; the final diagnosis was primary systemic AL amyloidosis with severe cardiomyopathy, resulting in a fatal outcome within eight months from the diagnosis.

Aim: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment., Methods: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05)., Results: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up., Conclusion: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.

Objective: To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients., Methods: One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05)., Results: Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection., Conclusion: Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.

Aim: Predictive value of serum b2-microglobulin (b2m) levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM)., Methods: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB., Results: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3+/-2.6 vs 3.8+/-3.4 mo, P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03)., Conclusion: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment, compared to baseline ones, might be a predictor of risk for VB.

The role of serum uric acid (SUA) in the context of adverse cardiovascular events in hypertensive subjects is controversial. Additionally, the relationship between SUA and indices of target organ damage is not well defined in this setting. Towards this end, we studied 842 consecutive nondiabetic patients with stage I-II essential hypertension (office blood pressure=148/95 mmHg, aged 53.4 years), referred to our outpatient hypertensive unit within a period of 4 years. According to the urinary albumin excretion (UAE), the study population was classified into those with microalbuminuria [MA(+), UAE=20-200 mg/24 h, n=222] and those without MA [MA (-), UAE< 20 mg/24 h, n=620]. Moreover, according to the presence of left ventricular hypertrophy (LVH) the participants were subdivided into two additional groups: [LVH (+), n=305 and LVH (-), n=537]. SUA levels were higher by 0.4 mg/dl, (P=0.04) in group MA (+) compared with the group MA (-), while no difference was observed between groups LVH (+) and LVH (-) (P=NS). In the entire population, SUA was correlated with body mass index (BMI) (r=0.17, P<0.001), waist/hip ratio (r=0.3, P<0.001), office systolic blood pressure (SBP) (r=0.14, P<0.05), triglycerides levels (r=0.25, P<0.001), UAE (r=0.35, P<0.001) and HDL (r=-0.26, P<0.001). Multiple regression analysis demonstrated that SUA was significantly related with BMI, office SBP and UAE (P<0.05). In conclusion, increased SUA levels are associated with MA but not with LVH in essential hypertensive subjects. Whether these inter-relationships may elucidate the clinical positioning of augmented SUA in this setting remains to be clarified in future studies.