New data concerning the epidemiology of Hepatitis B virus infection in Greece.

There is an obvious, significant, and diachronic reduction of the prevalence of HBV infection in Greece, concerning the general population as well as some traditionally high-risk groups, mainly as a result of constant informing and the widespread initiation of preventive and prophylactic measures, as well as the improvement of health care services. Nevertheless, there are special groups and populations (economical refugees, religious minorities, HIV-positive patients, abroad pregnant women, prostitutes, etc.) who represent sacs of high HBV endemicity and need epidemiological supervision and intervention, in order to limit the spread of the infection and to further improve the existing epidemiological data.

Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin.

BACKGROUND: The aim of this study was to investigate the effect of patient's age on the impact of typically proposed predictors of sustained virological response (SVR) in treatment-naïve, high-pretreatment viral load (>700.000 IU/ml), chronic hepatitis C (CHC) patients treated under real-life conditions in Greece. METHODS: We retrospectively analyzed 185 CHC patients (14.4% cirrhotics) who had been treated with weight-adjusted dosing (1.5 microg/kg per week) of pegylated interferon-a2b (PEG) plus genotype-based ribavirin (RIB) for 24 or 48 weeks of treatment, based on viral genotype. SVR was confirmed by undetectable serum HCV-RNA 6 months after the end of treatment. RESULTS: Overall, 68.5% of patients exhibited SVR and 31.5% were non-responders (non-SVRs). Among the non-SVRs, 71.4% were infected with HCV genotype-1. Importantly, 71.4% of genotype 4-infected treated patients exhibited SVR. In the multivariate analyses, only the early histological stage of liver disease (p=0.015) and the presence of genotype non-1 infection (p=0.003) were independent predictors of SVR. For patients younger than 35 years, none of the baseline parameters and neither viral genotype (p=0.284) nor the stage of liver disease (p=0.351) was an independent predictor of non-SVR, whereas for patients between 35 and 55, only the presence of genotype-1 infection independently predicted non-SVR (p=0.008). For older patients (>55 years), only the histological stage of liver disease (p=0.047) and not the viral genotype (p=0.275) independently predicted non-SVR. CONCLUSIONS: The impact of the typical predictors of SVR, such as viral genotype and liver histopathology, is modified according to patient's age in currently approved combination treatment.

Serological and virological profile of chronic HBV infected women at reproductive age in Greece. A two-year single center study.

OBJECTIVE: Seroprevalence of HBsAg in 26,746 women at reproductive age in Greece and evaluation of HBeAg/anti-HBe serological status as well as serum HBV-DNA levels in a subgroup of HBsAg(+) women at labor. STUDY DESIGN: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was calculated using a sensitive quantitative PCR assay, with a lower limit of quantification of 200 copies/ml. RESULTS: Overall, 1.53% of women were HBsAg(+) and the majority of them (64.96%) were Albanian. Among Albanian women the mean prevalence of HBsAg was 4.9%, 5.57% among Asian women, and 1.29% among women from Eastern European countries. The prevalence of HBsAg among African (0.29%) and Greek women (0.57%) was very low and significantly lower in comparison with the mean value of the studied population. Only 2.67% of HBsAg(+) women were HBeAg(+). Of a subgroup of women in labor with available serum samples 28.6% had undetectable levels of viremia (<200 copies/ml) and 15.9% had extremely low levels of viral replication (<400 copies/ml). Only 12.7% of pregnant women evaluated at labor exhibited extremely high serum HBV-DNA levels (>10,000,000 copies/ml) whereas 42.8% of them exhibited HBV-DNA levels between 1500 and 40,000 copies/ml. CONCLUSIONS: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher among specific ethnic populations (Asian, Albanian). The HBeAg(-)/antiHBe(+) serological status is a finding observed in the vast majority of HBsAg(+) women of our study population, and a significant percentage of them (approximately 44.5%) exhibit extremely low or even undetectable levels of viral replication at labor, suggesting possibly that only a proportion of HBsAg(+) women in Greece exhibit an extremely high risk of vertical transmission of the infection.

Impact of shorter duration of treatment on virological response rate in genotype 2 or 3 chronic hepatitis C virus infection.

OBJECTIVE: To evaluate the effect of shortened duration of pegylated interferon (PEG-IFN) and ribavirin (RIB) treatment on sustained virological response (SVR) rates in treatment-naomicronve patients with chronic hepatitis due to genotype 2 or 3 hepatitis C virus (HCV) infection and high pre-treatment viral load (>800,000 IU/mL). METHODS: Records of 142 patients with chronic hepatitis C (22 with cirrhosis) who had been treated with PEG-IFN and RIB for 24 weeks (Group A, n=88), both drugs for 12-16 weeks (Group B, n=39), or with PEG-IFN for 12-16 weeks and RIB for 24 weeks (Group C, n=15), were analyzed retrospectively. RESULTS: Overall, 81.7% of patients had SVR (Group A: 88.6%, Group B: 69.2% and Group C: 73.3%, p=0.02). Failure to achieve SVR was significantly related to treatment group (p=0.026 for Group B and p=0.002 for Group C, versus Group A), older age (p=0.023), higher liver biopsy stage (p=0.001) and presence of cirrhosis (p< 0.0001). In patients without cirrhosis, only the treatment group (p=0.018 for Group B and p=0.002 for Group C, compared to Group A) independently predicted failure to achieve SVR. CONCLUSION: Shorter duration of PEG-IFN treatment (12-16 weeks) adversely affected the SVR rate in patients with genotype 2 or 3 HCV infection. However, increasing the duration of RIB administration (12-16 weeks versus 24 weeks) in such patients did not have any beneficial effect on SVR in patients receiving short-duration PEG-IFN.

Changing serological status and low vaccination-induced protection rates against hepatitis B characterize chronic hepatitis C virus-infected injecting drug users in Greece: need for immunization policy.

OBJECTIVE: To evaluate the serological status of hepatitis B virus infection among Greek injecting drug users with chronic hepatitis C virus infection; to correlate hepatitis B virus infection status with the possible time of infection and the principal genotype of hepatitis C virus infection. METHODS: Two hundred and thirty consecutive injecting drug users with chronic hepatitis C virus infection were evaluated for serological markers of hepatitis B virus infection. One hundred and three of them (44.8%) reported intravenous drug use beginning before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical analysis of data was based on Student's t-test and chi analyses. RESULTS: Eighty-five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had serological markers of previous hepatitis B virus infection (P<0.001). Eleven patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients and 16.5% (21/127) of group B had vaccination-induced protective antibody levels (anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B, P=0.42). The percentages of patients infected with genotype-1 were also comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A significantly higher percentage of group A patients were infected with genotype-4 (19.7%) than those in group B (4.9%, P=0.02). CONCLUSION: The serological profile of hepatitis B virus infection among Greek hepatitis C virus-infected injecting drug users is changing. The proportion of successfully vaccinated hepatitis B virus injecting drug users, although significantly higher than the previous decades, is still relatively low. Vaccination policy in this high-risk group for viral hepatitis is urgently needed.

Serum procalcitonin levels in chronic hepatitis C patients under pegylated interferon-alpha plus ribavirin treatment.

OBJECTIVES: To evaluate the alterations of serum procalcitonin (PCT) levels in patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa) plus ribavirin (RIB) treatment and to correlate them with clinical and virological outcomes. STUDY DESIGN: Fifty-two consecutive patients (29 males, age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics) were evaluated for PCT levels at baseline and during the treatment course (at week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and again 6 months after completion of treatment. RESULTS: Two patients exhibited culture-proved bacterial infections during the treatment course. Thirty-six patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout the follow-up period except those two who exhibited bacterial infections during the treatment course. Virological responders exhibited significant decline of serum PCT levels over time compared to non-responders (p<0.001), even when adjusted for multiple baseline parameters (p=0.037). CONCLUSION: Serum PCT levels decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment, especially in the sustained virological responder group, while they elevate only when bacterial infections complicate the treatment course.

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients: the effect of pegylated interferon plus ribavirin treatment.

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.

Serological profile and virological evaluation of hepatitis B and hepatitis C virus infection among HIV infected patients in Greece.

In this study we evaluate the prevalence of HBV and HCV infections and the HBV and/or HCV viral load as well as HCV genotype among 737 HIV-infected patients. 89/737 (12.1%) were HBsAg(+) and the majority of them (60.7%) were HBeAg(+), in contrast to general Greek population; anti-HBc seropositivity was detected in 48.1% of the study population. Serum HBV-DNA levels were 5.75 +/- 1.66 (-log 10 copies/ml) and HBeAg(+) coinfected patients had significantly higher levels than HBeAg(-) ones (7.40 +/- 0.64 vs 4.59 +/- 1.01, respectively, p < 0.001). 8.2% of HIV-infected patients were anti-HCV(+) and the majority of them (85.7%) had HCV-RNA levels more than 700.000 IU/I. The most common HCV-genotype was genotype-1 (12/28, 42.9%), representing a difficult-to-treat special population.

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease.

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.

Late onset autoimmune thrombocytopenia associated with pegylated interferon-alpha-2b plus ribavirin treatment for chronic hepatitis C.

Interferon-induced, immune-mediated, thrombocytopenia is a rare event. In this report the case is described of development of severe, reversible, autoimmune thrombocytopenia in a patient with chronic hepatitis C virus infection, 6 months after the discontinuation of pegylated interferon-alpha-2b plus ribavirin treatment. Physicians must be aware that autoimmune thrombocytopenia can occur even after the end of treatment, as a late onset complication, especially when using the pegylated forms of interferons, which have longer half-lives and prolonged activity.

Serological profile of HBV infection and liver histopathology among injecting drug users with chronic HCV infection in Greece.

BACKGROUND: The aim of this study was to evaluate the serological status of HBV infection and liver histology in chronic HCV-infected injecting drug users (IDUs) and to correlate them with the possible time of infection and the principal HCV genotype. METHODS: Some 130 prior IDUs with chronic HCV infection were consecutively evaluated for the serological status of HBV infection. Fifty-eight (44.62%) reported intravenous drug use beginning before 1992 (group A) and 72 (55.38%) after 1992 (group B). HCV genotyping was available in 86 patients (PCR). Liver biopsy was performed in 48 patients (Ishak scoring system). There was no available data about alcohol consumption in the study population. Statistical analysis was based on the t-test and the chi(2) test (p<0.05). RESULTS: Some 82.8% of group A patients had previous HBV infection, whereas only 22.2% of group B patients did (p<0.001). Among group A patients, 10.3% were HBV-seronegative whereas 61.1% of group B patients were (p<0.001). Only 3.4% of group A patients were HBV-vaccinated compared to 16.7% in group B (p=0.016). HCV genotype was not associated with HBV serological status. No significant differences were detected in age, sex, possible time of infection, HBV serological status, or HCV genotype among those with higher vs. lower total grading scores. Seventy-five percent of patients had mild or no detectable fibrosis unrelated to the possible period of infection, the HBV serological status, and the HCV genotype. CONCLUSIONS: The serological profile of HBV infection is changing among Greek chronic HCV-infected IDUs, while the percentages of successfully HBV-vaccinated IDUs are relatively low. Severe liver disease is an uncommon finding in these patients, irrespective of the possible time of infection, the HBV serological status, and the HCV genotype.

HBeAg negative serological status and low viral replication levels characterize chronic hepatitis B virus-infected women at reproductive age in Greece: a one-year prospective single center study.

AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13 581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe status as well as serum hepatitis B virus (HBV)-DNA levels in a subgroup of HBsAg(+) pregnant women at labor in Greece. METHODS: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive quantitative PCR assay. Statistical analysis of data was based on parametric methodology. RESULTS: Overall, 1.156% of women were HBsAg(+) and the majority of them (71.3%) were Albanian. The prevalence of HBsAg was 5.1% in Albanian women, 4.2% in Asian women and 1.14% in women from Eastern European countries. The prevalence of HBsAg in African (0.36%) and Greek women (0.29%) was very low. Only 4.45% of HBsAg(+) women were also HBeAg(+) whereas the vast majority of them were HBeAg(-)/anti-HBe(+). Undetectable levels of viremia (<200 copies/mL) were observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low levels of viral replication (<400 copies/mL). Only two pregnant women exhibited extremely high serum HBV-DNA levels (>10 000 000 copies/mL), whereas 32.26% exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher enough among specific populations. The HBeAg(-)/anti-HBe(+) serological status and the extremely low or even undetectable viral replicative status in the majority of HBsAg(+) women of our study population, suggest that only a small proportion of HBsAg(+) women in Greece exhibit a high risk for vertical transmission of the infection.

Relationship between serum b2-microglobulin levels and virological breakthrough in HBeAg-negative chronic hepatitis B patients, under long-term treatment schedules including lamivudine.

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.

Serum beta2-microglobulin levels in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy: relationship with virological breakthrough.

OBJECTIVES: To evaluate the predictive value of serum beta2-microglobulin (beta2m) levels for virological breakthrough in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy. METHODS: Serum beta2m levels were calculated at baseline and every three months during lamivudine monotherapy in 25 patients with chronic hepatitis B, using microparticle enzyme immunoassay technology to investigate their association with biochemical, virological and histological outcome data. Cox proportional hazard models were used to investigate the association between serum beta2m levels and virological breakthrough. RESULTS: Seven of 25 (28%), nine of 25 (36%) and 14 of 25 (56%) chronic hepatitis B patients exhibited virological breakthrough at months 12, 24 and 36 of treatment, respectively. All chronic hepatitis B patients who did not show virological breakthrough in the follow-up period exhibited beta2m elevation in month 3 of treatment. The duration (in months) of serum beta2m elevation was significantly higher in the responders group than the nonresponders group (7.3 +/- 2.6 versus 3.8 +/- 3.4, P=0.02). In contrast to patients whose serum beta2m levels were increased at three months, patients whose beta2m levels were decreased had a 4.6 times higher risk of experiencing virological breakthrough (hazards ratio 4.6, 95% CI 1.22 to 17.36). When age, pretreatment serum alanine aminotransferase and hepatitis B virus DNA levels, and grade of liver disease were simultaneously included in the same Cox model, decreased beta2m status was still associated with increased risk of virological breakthrough (hazards ratio 12.2, 95% CI 1.28 to 116.8). CONCLUSIONS: In hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy, serum b2m levels at three months of treatment, compared with baseline levels, are good predictors of risk for virological breakthrough.

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.