Nutrient Status in Patients with Frequent Episodic Tension-Type Headache: A Case-Control Study.

OBJECTIVE: To investigate the relationship between frequent episodic tension-type headache (FE-TTH) and 25-hydroxyvitamin-D (25(OH)D), folate, vitamin B12, and magnesium. DESIGN-METHODS: A prospective case-control study involving adults with FETTH and age-sex matched healthy controls (HC) was performed. Individuals under the responsibility of the three provincial Health Centres of the prefecture of Trikala (Central Greece) were recruited during their regular check-up visits. The relationship between FETTH and serum levels of 25(OH)D, vitamin B12, folate, and magnesium was investigated (primary outcomes). Demographics, daily habits, somatometrics, psychometric and sleep quality measurements, laboratory indices, cardiovascular comorbidities and medications taken were also recorded and compared (secondary outcomes). Potential associations of the above-listed parameters with headache parameters (headache frequency, severity and analgesic consumption) were also examined (secondary outcomes). RESULTS: Between September and December 2020, 30 patients with FETTH and 30 HC were successfully recruited. Demographics, comorbidities, regular medications, smoking habits, alcohol and coffee consumption, body mass index measurements, markers of systemic inflammation, folate and vitamin B12 levels were similar between the two groups (P>0.05). Lower serum 25(OH)D was both univariately (P<0.001) and multivariately [OR= 0.72, 95%CI=(0.55, 0.94) per 1ng/ml increase] associated with FETTH, while serum magnesium was found lower in FETTH only according to the univariate approach (P=0.036). Higher levels of depression (P=0.050) and anxiety (P=0.020), as well as poor quality of sleep (P=0.008), were univariately associated with FETTH. Only the effect of anxiety remained significant following the multivariate logistic regression [OR=7.90, 95%CI=(1.00, 62.47)]. Headache parameters were not associated with any one of the assessed variables. DISCUSSION: Lower serum 25(OH)D was related to the presence of FETTH. This finding could imply a potential role for vitamin D in the pathophysiology of TTH.

Association of antiviral therapy with reduced disease progression in chronic Hepatitis B patients: Results from a nation-wide cohort study.

BACKGROUND AND AIMS: Although effective treatment in terms of inducing virological and biochemical response for chronic hepatitis B (CHB) is available, its effect on the clinical course of the disease has not yet been accurately estimated. Objective of this study was to evaluate the effect of antiviral therapy and its type [interferon +/- nucleos(t)ide analogs (NAs) vs. NAs] on the occurrence of a clinical event (liver decompensation, liver transplant, hepatocellular carcinoma and death from a liver-related cause) in CHB patients. METHODS: The study population was derived from the HEPNET-Greece, a nationwide cohort study aimed to evaluate the current epidemiological course of viral hepatitis. To account for time-dependent confounding, Cox marginal structural models were used to analyze data. RESULTS: Thirty out of 2,125 eligible patients experienced a clinical event during their follow-up. When comparing treated to untreated individuals, the hazard ratio (HR) for a clinical event was 0.39 (95% CI: 0.16-0.98; p =0.044) in the whole sample, whereas there were indications of a more intense effect in the subgroup of patients with cirrhosis at presentation (HR =0.16, 95% CI: 0.02-1.21; p =0.075). The effect of Interferon initiated treatment was not significantly different of that of NAs. There was some evidence, albeit not statistically significant, of a protective treatment effect on hepatocellular carcinoma development (HCC). CONCLUSIONS: Data from observational studies can provide useful inference, provided they are analyzed appropriately. The current study has shown that the available treatment options for CHB offer a significant clinical benefit to CHB infected individuals. Hippokratia 2016, 20(3): 214-221.

Significant epidemiological changes in chronic hepatitis C infection: results of the nationwide HEPNET-GREECE cohort study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is an important health problem worldwide. The aim of the study is to describe the baseline characteristics and possible epidemiological changes of the patients with chronic HCV infection included in a nationwide Greek study. PATIENTS AND METHODS: two thousand eight hundred seventeen (2817) patients, followed-up at 20 hepatology centres throughout Greece between the years 1997 and 2006 were enrolled in the study. RESULTS: Intravenous drug use (IDU) and history of blood transfusion prior to 1992 was reported in 30.7% and 22.6% of our patients, respectively. In 1865 (66.2%) patients with known genotypes, the distribution for genotype 1, 2, 3 and 4 was 45.1%, 7%, 34% and 13.9% respectively. Genotype 1 was more common in older people, in women (55.9% p<0.001) and patients with transfusion-related hepatitis (61.6% p<0.001). Genotype 3 was more common in younger patients, in men (43% p<0.001) and in IDUs (63.3% p<0.001). A significant reduction of transfusion-related hepatitis C incidence (p<0.001) in conjunction with the proportion of genotype 1 (p<0.001) was observed during the last three decades while an increase in IDU infected patients and genotype 3 was detected. CONCLUSIONS: Our study showed a significant change in HCV genotype distribution and source of HCV infection during the last three decades and under that scope, urgent actions are needed in order to control the spread of HCV infection.

Health-related quality of life in Greek chronic hepatitis C patients during pegylated interferon and ribavirin treatment.

UNLABELLED: Background - Aims: Chronic hepatitis C (CHC) can cause a series of neuropsychiatric symptoms, whereas the currently approved treatment for this disease often induces similar symptoms as well. The aim of the present study was to compare Greek CHC patients' health-related quality of life (HRQoL) with that of healthy controls, to identify any possible relationships between HRQoL and demographic and laboratory parameters and to study the fluctuation of HRQoL during therapy and follow-up. PATIENTS AND METHODS: Ninty nine patients with CHC and 91 healthy controls were enrolled in the study. ALT, viral load, HCV genotype, fibrosis stage by liver biopsy and BMI, were determined at baseline. All patients completed the SF-36 quality of life questionnaire, which was self-administered, before treatment. They were treated with pegylated interferon alpha2-a or alpha-2b and ribavirin for 24 or 48 weeks and evaluated in the middle of therapy, at the end and six months after treatment cessation. SF-36 questionnaire was also completed in each evaluation. RESULTS: Patients' HRQoL was found to be below that of healthy controls in all SF-36 scales before treatment. There was a significant negative association between history of drug abuse and general health and a positive association between age and mental health. Multivariate analysis revealed that history of drug abuse seemed to play a significant role in bodily pain and general health of patients, as well as age did in vitality and mental health. The course of patients' HRQoL showed that in the middle of treatment values in all SF-36 scales were below those of baseline and they returned to pretreatment levels at the end of therapy. However, at the end of the six month follow-up period, an improvement in almost all scales compared to baseline was noted. CONCLUSION: Our results showed that a) Greek CHC patients' HRQoL was worse than that of healthy individuals and fluctuated significantly during treatment b) A history of drug abuse and age can independently affect HRQoL c) During treatment values of HRQoL are worsened possibly due to interferon-a treatment and d) In the long-term treatment results in improvement of HRQoL.

Epidemiology, course and disease burden of chronic hepatitis B virus infection. HEPNET study for chronic hepatitis B: a multicentre Greek study.

SUMMARY: Hepatitis B virus infection (HBV) has been recognized as a major health problem worldwide. Greece belongs to the intermediate endemicity countries with a trend of decreasing prevalence of HBV infection during the last decade. However, the recent massive immigration to our country may have led to alterations of HBV epidemiology. In this study, we evaluated the epidemiological features of HBV infection in a sample of 3480 patients followed up during the years 1997-2006. Immigrants mainly from Albania represented the 18.6% of the total study population and 56.6% of children. The majority of the patients had no family history of HBV infection (67.3%) or of acute hepatitis (95.4%), no known source of infection (64.6%), with intrafamilial spread accounting for 16.9% of the HBV transmission in adults and 33.9% in children. HBeAg(-) hepatitis B was the predominant form of hepatitis (92.1%) among the Greek patients in contrast to the immigrants where 16.6% were HBeAg(+). Liver cirrhosis was diagnosed in 8.8% of the total population and 0.9% had hepatocellular carcinoma. A high proportion of children were HBeAg(+) (62%), 55% from immigrant families, 25.2% were infected in the perinatal period and had no evidence of disease complications. In conclusion our results showed (a) a changing pattern in the epidemiology of HBV infection in Greece due to the significant number of HBeAg(+) patients, especially among children and (b) a considerable number of patients although aware of their infection, present with advanced disease.

Treatment of intravenous drug users with chronic hepatitis C: treatment response, compliance and side effects.

BACKGROUND: Although intravenous drug users (IVDUs) comprise the majority of patients with chronic hepatitis C, most of them are excluded from treatment because of concerns about adherence to treatment and side effects. MATERIAL AND METHODS: In this study we retrospectively evaluated safety, compliance to treatment and efficacy of treatment in IVDUs with HCV infection in 163 former IVDUs with chronic hepatitis C, who were not in methadone substitution and were attending our clinics the period 1997-2004. All subjects were HCVRNA (+), had ALT levels>x1.5 UNL and were treated for their HCV infection. Treatment consisted of three different regimens: IFN-alpha monotherapy (39.8%), IFN-alpha/ribavirin combination therapy (30.1%) and pegylated IFN-alpha/ribavirin combination therapy. RESULTS: Eighty seven over 163 patients (53.3%) discontinued treatment early due to drug abuse relapse (62%), side effects (32.1%, 10% psychiatric) and 5,7% for other reasons. Eighty precent of those who discontinued treatment had pre-treatment drug abstinence/= 9 months.

The effect of adherence to therapy on sustained response in daily or three times a week interferon alpha-2b plus ribavirin treatment of naive and nonresponder chronic hepatitis C patients.

The aim was to demonstrate adherence to treatment has been suggested to enhance rates of sustained response in patients with hepatitis C. In this study, we evaluated the effect of drug dosage reduction or the duration of the expected therapy in patients treated with interferon (IFN)-alpha2b plus ribavirin. Virologic response rates were re-analysed according to compliance to therapy in (i) 301 naive and (ii) 142 nonresponders to previous IFN therapy treated with either IFN 5 MU TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks plus ribavirin or IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks plus ribavirin. Patients were separated into those who adhered to > or =80% of their intended treatment schedule (dose of both drugs and duration) and those who did not. Compliance to treatment resulted in significantly higher response rates in both groups of patients: 43.93% compared with 6.90% of noncompliant naive patients and 30.77% compared with 10.53% of nonresponder patients. Compliance to treatment was found to have a similar effect when the results were analysed according to HCV genotype. Our findings suggest that compliance to treatment for > or =80% of the intended treatment schedule results in significantly higher sustained response rates in both naive and nonresponder patients. Consequently, every effort should be made to improve patient adherence to therapy.

A randomized trial to assess the efficacy of interferon-alpha daily in combination with ribavirin in the treatment of naïve patients with chronic hepatitis C.

A randomized trial was conducted to assess the efficacy of interferon-alpha (IFN) daily in combination with ribavirin in 301 naïve patients with chronic hepatitis C (CHC). Patients were randomized to receive ribavirin 1.2 g daily (QD) for 48 weeks with either IFN 5 MU (thrice weekly) TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks (IFN TIW, n = 154) or IFN 5 MU QD for 8 weeks followed by IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks (IFN QD, n = 147). Treatment discontinuation rates, because of adverse events, were similar in the two arms (14.9% in IFN TIW and 14.3% in IFN QD, P = 0.87). The proportion of patients with sustained virological response (SVR) was 27.9% for patients treated TIW and 38.8% for those treated QD (P = 0.046). According to logistic regression analysis, patients in the IFN QD arm had 1.7 times higher probability of achieving SVR, than those receiving IFN TIW (P = 0.038). Low baseline viral load (P = 0.017) and genotype non-1 (P = 0.036) were associated with higher SVR rates. Combination of IFN/ribavirin for 48 weeks is more effective when IFN is administered daily for the first 24 weeks in naïve patients with CHC.

A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1.

A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.

Development and assessment of a novel real-time PCR assay for quantitation of HBV DNA.

HBV DNA quantitation is used extensively for the monitoring of treatment of hepatitis B virus (HBV) infection. The aim of this study was to develop a highly sensitive and reproducible real-time PCR (RTD-PCR) assay for the quantitation of HBV DNA using the LightCycler system. The performance of this assay was assessed by analyzing serial dilutions of HBV genomic DNA of known concentration and the lower limit of detection was found to be 1 DNA copy/reaction. By using serial dilutions of plasmid standard, RTD-PCR was determined to quantify HBV DNA in a 10-log10 dynamic range. RTD-PCR was found to be more sensitive than the commercially available tests such as the Quantiplex HBV DNA and the AMPLICOR HBV MONITOR assays. The median coefficient of variation of interexperimental variability was 3.2%. The HBV DNA values obtained with RTD-PCR were highly correlated with assays available commercially. These findings suggest that our RTD-PCR assay combines high sensitivity and reproducibility for HBV DNA quantitation in an incomparable high dynamic range of quantitation.

Changes of hepatitis B core antigen (HBcAg) in liver biopsies of patients with chronic active hepatitis B treated with interferon.

Data have shown that hepatitis B core antigen (HBcAg) is detected in both the hepatocyte nucleus and cytoplasm. Its expression is associated with chronic hepatitis and active viral replication. The intrahepatic distribution of HBcAg was studied in liver biopsies of 14 patients with chronic active hepatitis B (CAH-B) (5 were hepatitis B e antigen [HBeAg]+/anti-HBe--, 9 were HBeAg--/anti-HBe+) by an immunohistochemical method (PAP) before and after 6-month treatment with interferon (IFN), and our findings were analyzed according to the response of patients to treatment. Our findings showed that, at the end of treatment, nuclear HBcAg was decreased or absent in 4 of 5 and cytoplasmic HBcAg in 2 of 4 HBeAg+/anti-HBe--patients, irrespective of the response to treatment. Loss of cytoplasmic expression was related to the outcome of treatment in 5 of 9 HBeAg--/anti-HBe+ patients. Four patients expressed no HBcAg before or at the end of treatment. These findings possibly reflect a different pattern of viral core antigen expression as a result of IFN therapy in the two groups of patients.

Interferon treatment of chronic active hepatitis B: effect of a six month treatment regimen.

In this study of 17 patients with chronic active hepatitis B, the loss of hepatitis B virus DNA, the return to normal of alanine aminotransferase activities, and histological improvement after six months' treatment with 3 million units three times weekly with interferon alfa-2b, was achieved in 40% of hepatitis B e antigen (HBeAg) positive/anti HBe negative patients, and 41.66% of HBeAg negative/anti HBe positive patients. The reappearance of hepatitis B virus DNA was seen in most patients when treatment was stopped, although a higher percentage of HBeAg positive/anti HBe negative patients (20%) had a sustained loss of hepatitis B virus DNA, return to normal alanine aminotransferase activities, and histological improvement compared with HBeAg negative/anti HBe positive patients (8.3%).

Physiological variations of T cells during the menstrual cycle.

Peripheral blood T lymphocytes were measured in healthy subjects during the various phases of the menstrual cycle. A significant decrease in T lymphocytes occurred during the menstrual period; T-lymphocyte numbers returned to the pre-levels 1 week after the end of the menstrual period.