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E K Manesis

Publications and source records attributed to E K Manesis.

17 recordsLinked to original sources
PubMed2006

A partially overlapping treatment course with lamivudine and interferon in hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-) with interferon or lamivudine alone is inefficient and reports of combination treatment with both drugs, equivocal so far. AIM: To investigate the efficacy of a lamivudine-interferon combination therapy in 36 patients HBeAg-negative CHBe-. METHODS: Lamivudine was administered from 1 to 12 months and interferon-alpha2b from 7 to 18 months. A historical control group of 36 CHBe- patients, matched for age and sex and treated with the same dosage of interferon-alpha2b was used. All patients were followed up for > or =12-month post-treatment. RESULTS: The biochemical response rate at the end of treatment was 78% in lamivudine-interferon and 52.8% in interferon-control group (P = 0.026) and at 12-month post-treatment 38.9% and 22.2%, respectively (P = 0.125). Alanine aminotransferase normalization and serum HBV-DNA levels < or =30 000 cp/mL were observed in 50.0% of lamivudine-interferon-treated and 30.6% of interferon-treated patients at the end of treatment (P =0.093) and in 22.2% and 13.9% of patients, respectively, at 12-month post-treatment (P = 0.358). Moreover, alanine aminotransferase normalization and undetectable serum HBV-DNA (<400 cp/mL) was observed in 30.6% of lamivudine-interferon-treated and 8.3% of interferon-treated patients at the end of treatment (P = 0.017) and in 8.3% and 0% of patients, respectively, at 12-month post-treatment (P = 0.076). CONCLUSIONS: In CHBe-, 12 months after ending a lamivudine-interferon partially overlapping 18-month combination course, 22% of patients still maintain normal alanine aminotransferase and HBV-DNA levels < or =30 000 cp/mL. However, a 12-month interferon monotherapy course may achieve similar responses.

Adolescent↗
PubMed2006

Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis.

Diabetes mellitus has been reported to have an increased prevalence and to be associated with more severe fibrosis in patients with chronic hepatitis C. We evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis B or C as well as the possible association between presence of diabetes and extent of liver fibrosis. In total, 434 consecutive patients with histologically documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174) or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and epidemiological, somatomorphic, laboratory and histological patient characteristics were evaluated. Liver histological lesions were blindly evaluated according to the Ishak's classification. Diabetes was present in 58 (13%) patients, without any difference between those with chronic hepatitis B (14%) or C (13%). Diabetes was observed significantly less frequently in patients with fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The presence of diabetes was independently associated with higher gamma-glutamyl-transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P < 0.001) as well as with presence of hepatic steatosis and increased serum triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was significantly associated with older age and higher GGT levels, but not with the extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10% of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis C. The presence of diabetes is strongly associated with more severe liver fibrosis, but such an association may be related to the high prevalence of diabetes in patients with cirrhosis.

Alanine Transaminase↗
PubMed2005

Impact of interferon-alpha therapy on liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B.

The possible effect of interferon-alpha (IFNa) on liver fibrosis progression has not been adequately studied in chronic hepatitis B. We evaluated 147 patients with HBeAg-negative chronic hepatitis B who had > or =2 liver biopsies and had been treated with IFNa (n = 120) or had remained untreated (n = 27). The median interval between the two biopsies was 24 (12-160) months. All biopsies were scored blindly by a single liver histopathologist according to the classification of Ishak et al. (J Hepatol 1995; 22: 696-699). IFNa induced sustained biochemical response in 30, initial response and subsequent relapse in 57 and no response in 33 patients. Fibrosis improved in 17.5% of treated (sustained responders: 40%, relapsers: 9%, nonresponders: 12%) and 4% of untreated patients and worsened in 34% (sustained responders: 7%, relapsers: 40%, nonresponders: 48%) and 70% of cases, respectively (P = 0.002). The annual rate of fibrosis progression was worse in the untreated (0.427 +/- 0.119) than in treated patients (0.067 +/- 0.052, P = 0.001). However, the fibrosis progression rate in the untreated patients was not significantly different than the net fibrosis progression rate (after subtraction of IFNa duration) in nonresponders or relapsers. In multivariate analysis, worse fibrosis progression rate was associated with older age (P = 0.010), worse baseline grading score (P < 0.001), lower baseline fibrosis (P = 0.035) and the type of response to IFNa (P = 0.032). In conclusion, in HBeAg-negative chronic hepatitis B, IFNa significantly reduces the rate of fibrosis progression, but such an effect is mainly observed in patients with sustained biochemical responses. In relapsers and nonresponders, fibrosis benefit equals the treatment period. The strongest factor associated with fibrosis progression is the change in necroinflammatory activity.

Adult↗
PubMed2004

Deep sinus aspergillosis in a liver transplant recipient successfully treated with a combination of caspofungin and voriconazole.

We describe the rare case of a diabetic patient who was successfully treated for cytomegalovirus viremia and leishmaniasis following liver transplantation for hepatitis C virus-related cirrhosis, but also developed invasive sinus Aspergillus infection, while still on liposomal amphotericin B (AmBisome). The patient refused radical surgery including eye enucleation, and received a combination of intravenous caspofungin and voriconazole, along with repeated, conservative, local surgical debridement. At follow-up, 15 months after the onset of sinusitis, the patient remains culture-negative, fully active, and without evidence of local recurrence.

Adult↗
PubMed2001

Induction interferon therapy in naïve patients with chronic hepatitis C: increased end-of-treatment virological responses but absence of long-term benefit.

BACKGROUND AND AIMS: The low efficacy of interferon monotherapy and data from viral kinetic studies led us to evaluate the efficacy of interferon administered daily in chronic hepatitis C. PATIENTS AND METHODS: Thirty-eight naïve patients with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN-alpha daily for 1 month, followed by the same dose three times a week for 11 months. Results were compared to a three-times-a-week scheme of 3 MU IFN-alpha for 1 year. RESULTS: At the end of the induction period, 27 out of 38 (71%) patients had cleared HCV-RNA with a significantly higher rate in the 5 MU than in the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end-of-treatment virological response rate was 66% (25 out of 38) in the induction groups and 40% (10 out of 25) in the control group (P=0.04). Six months after completion of therapy, the sustained response rate dropped to 29% (11 out of 38) compared to 28% (7 out of 25) in the standard regimen. CONCLUSIONS: In chronic hepatitis C, treatment with 5 or 3 MU IFN-alpha daily during the first month of a standard IFN regimen leads to significantly increased end-of-treatment virological responses, but long-term responses are similar to those of standard IFN monotherapy.

Adult↗
PubMed2001

Interferon alpha treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND AND AIMS: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-), interferon (IFN) achieves very low biochemical sustained response rates. No information exists on retreatment. METHODS: Two hundred sixteen CHBe- patients treated for 5 or 12 months with 3 MU IFN-alpha2b thrice weekly and retreated (51 patients, 60 courses) because of no response or relapse were retrospectively analyzed. RESULTS: After 7.0 years of median follow-up, 39 naive patients (18.1%) were still in biochemical and virologic remission after a single IFN course. Longer treatment and a biochemical response within 4 months were significant predictors, inversely related to relapse by multivariate analysis (relative hazard [RH], 0.611; 95% confidence interval [CI], 0.448-0.834 and RH, 0.290; 95% CI, 0.192-0.438, respectively). Retreatment resulted in 18.4% sustained response by intention-to-treat (18 of 98 patients). Patients with sustained response had persistently normal alanine aminotransferase levels, undetectable hepatitis B virus (HBV) DNA by molecular hybridization, and significant improvement of histologic grade, and 32% of them lost hepatitis B surface antigen. In sustained responders, serum HBV DNA was undetectable or very low at the end of treatment and at the end of follow-up (median 3934 and 903 copies/mL, respectively) by quantitative polymerase chain reaction. CONCLUSIONS: IFN induced long-term biochemical and virologic remission in approximately 18% of naive or retreated patients with CHBe-. Sustained responders exhibited significant histologic improvement and a high rate of HBsAg loss.

Adult↗
PubMed1999

Oral ganciclovir treatment in chronic hepatitis B virus infection: a pilot study.

BACKGROUND/AIMS: Ganciclovir is a nucleoside analogue with an excellent safety record; it is effective against cytomegalovirus infection in both its intravenous and its oral form. Intravenous administration of ganciclovir is active against hepatitis B virus but the efficacy of oral ganciclovir is unknown. The aim of this study was to evaluate the tolerability and primary efficacy in reducing HBV DNA levels and liver enzymes of 2 dosing schedules of oral ganciclovir in HBeAg-positive and -negative patients with chronic hepatitis B. METHODS: Oral ganciclovir was administered to 15 consecutive patients with active chronic hepatitis B (age 43+/-12 years; 73% males; seven HBeAg-positive and eight negative; no cirrhosis) in a pilot, phase I, open-label study. Before treatment, all patients were screened for 8 weeks to ascertain the persistence of biochemical and virological activity, and then randomized to receive 3 g (eight patients), or 6 g (seven patients) of oral ganciclovir daily for 8 weeks; following therapy, they were closely observed for 8 more weeks. RESULTS: Baseline HBV DNA declined by 99% or 2 log10 at the end of treatment (405.0 vs 3.9 MEq/ml, respectively) and in four patients serum HBV DNA became undetectable by the Monitor assay. Oral ganciclovir suppressed HBV equally well in HBeAg-positive and -negative patients, and the 3- and 6-g daily dose regimens were equally effective. The pre-treatment viral load, however, was a determinant of response, with patients in the lowest quartile of baseline HBV DNA levels responding significantly better than those in the upper quartile (3.0 vs 0.6 log10 respectively, p=0.002). Serum alanine aminotransferase levels became normal or declined in most patients. Oral ganciclovir was very well tolerated. Within 8 weeks after stopping medication, a relapse in serum HBV DNA levels occurred in nine of the 15 patients (60%). CONCLUSIONS: These findings suggest that ganciclovir administered orally at a dose of 3 g can achieve sufficient suppression of HBV replication. This dose, and even higher doses, are well tolerated and could be used as an alternative or in combination with other antivirals for the treatment of chronic hepatitis B.

Administration, Oral↗
PubMed1998

Neurovisual impairment: a frequent complication of alpha-interferon treatment in chronic viral hepatitis.

Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN-a2b thrice weekly. Measurements included routine ophthalmologic evaluation and recordings of visual evoked responses (VER), electroretinograms (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant covariate associated with increased risk for an abnormal base-VER by multiple logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In 45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment VERs (end-VER) were significantly prolonged compared with baseline, becoming abnormal in 11 (15 of 74 eyes, 20.3%) (138.8+/-8.7 vs. 117.7+/-5.2 ms, P < .001). This subgroup had older age (59.1+/-11.0 vs. 47.5+/-15.3, P=.007) and reduced visual sensitivity compared with their own pretreatment measurements (24.5+/-1.6 vs. 23.0+/-1.2db, P=.019). Changes of end-VERs by age had a sigmoid distribution with a steep increase of values beyond the 5th decade (R2=.326, P < .001). In a logistic regression model, significant predictors of abnormal end-VERs were, patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and serum cholesterol levels above 240 mg% (RR 7.1 compared with values < 240 mg%). Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination revealed cotton wool spots in one other. ERG recordings and the P100 amplitude remained unchanged. After stopping IFN, the treatment-associated neurovisual abnormalities reversed to normal in 7 patients (10 of 15 eyes) and persisted in 5 (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients remaining clinically asymptomatic. In conclusion, subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.

Adult↗
PubMed1997

Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy.

The prevalence of antithyroid peroxidase antibodies (ATPO) and/or of thyroid dysfunction was studied in 422 patients with chronic viral hepatitis C, B, and D. Baseline results were compared with those during and 6 months after interferon alfa (IFN-alpha) therapy. The overall prevalence of ATPO among untreated patients was 14.1%, with no significant differences between chronic hepatitis C, B, or D, as well as between males and females. However, high ATPO titers (> or = 18 IU/mL) clustered significantly among females (8.7% vs. 3.4%; P = .022), especially those with chronic hepatitis C (11.2% vs. 3.6%; P = .036). Before treatment, 3.7% of the patients had thyroid dysfunction, mostly hypothyroidism (3.5%), the latter increasing to 14.3% among patients with ATPO titers > or = 18 IU/mL. IFN-alpha treatment significantly increased overall thyroid dysfunction (9.7%; P = .001) and hypothyroidism (7.8%; P = .01), particularly among patients with high baseline ATPO (38.5%; P = .0002). Six months after stopping IFN-alpha treatment, the prevalence of thyroid dysfunction was 8.0%, still significantly higher than at baseline. By multivariate analysis, the only predictor positively associated with pre- or on-treatment hypothyroidism was the baseline titer of the ATPO antibodies (relative risk [RR], 3.0 and 3.8 per each log titer increase, respectively). In conclusion, patients with chronic viral hepatitis on IFN-alpha treatment exhibit an almost threefold increase of baseline thyroid dysfunction, persisting long after the end of therapy. High ATPO titers, clustering among females, particularly those with hepatitis C, represent the only predictor of pre- and on-treatment hypothyroidism by multivariate analysis. Patients with chronic viral hepatitis, especially females, should be tested for ATPO and thyroid function and monitored during and posttreatment for free thyroxin (FT4) and thyroid-stimulating hormone (TSH) levels.

Adolescent↗
PubMed1997

Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: a 4-year follow-up of 211 patients.

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.

Adolescent↗
PubMed1997

Computer image analysis of ultrasound images for discriminating and grading liver parenchyma disease employing a hierarchical decision tree scheme and the multilayer perceptron neural network classifier.

Differential diagnosis of liver parenchyma disease and grading of the hepatic disease on ultrasound is a common radiological problem that influences patient management. The aim of this study was to apply image analysis methods on ultrasound images for discriminating liver cirrhosis from fatty liver infiltration and for grading hepatic disease, which is important in the management of the patients. Ultrasound images of histologically confirmed 18 livers with cirrhosis, 37 livers with fatty infiltration, and 24 normal livers of healthy volunteers were selected and were digitized for further computer processing. Twenty two textural features were calculated from small matrix samples selected from the ultrasound image matrix of the liver parenchyma. These features were used in the design a three level hierarchical decision tree classification scheme, employing the multilayer perceptron neural network classifier at each hierarchical tree level. At the first tree level, classification accuracy for distinguishing normal from abnormal livers was 93.7%, at the second level the accuracy for discriminating cirrhosis from fatty infiltration was 90.9%, and at the third level the accuracy in distinguishing between low and high grading liver cirrhosis or fatty infiltration was 94.1% and 84.9% respectively. The proposed computer software system may be of value to the radiologists in assessing liver parenchyma disease.

Decision Trees↗
PubMed1995

Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: a randomized, controlled trial.

We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for patients with hepatocellular carcinoma (HCC). Eighty-five consequent, previously untreated HCC patients with inoperable disease, were randomized to receive the luteinizing hormone-releasing hormone (LR-RH)-analogue triptorelin and the antiestrogen tamoxifen (33 patients) or triptorelin plus the antiandrogen flutamide (23 patients), or only placebo (29 patients) in a double blind fashion. All groups were comparable as to age, sex, tumor extension, underlying cirrhosis and biochemical parameters. The tamoxifen (TMX) group had a significantly longer survival (282 days) compared with flutamide (112 days) and with placebo (127 days) groups (P = .0238, log rank test). The upper quartile of patients in the TMX group lived 384 days or longer, and most of them (57.1%) were women (P < .0005), in contrast to the upper quartile of the placebo (170 days, 16.7% women) and the flutamide group (134 days, 33.3% women). The calculated tumor volume doubling time (TVDT) was significantly higher in the TMX group (296 days) than in the other two groups (99 and 101 days for placebo and flutamide groups, respectively, P = .023). In a Cox proportional hazards model, the TMX treatment, along with the baseline Okuda's HCC stage, the hepatitis B surface antigen, the portal vein diameter, the carcino embryonic antigen (CEA) and a self-assessment score of quality of life, were covariates predicting survival. Although the degree of serum sex hormone suppression was not a significant predictor of survival, the interaction of female sex and TMX treatment, it was (P = .0052).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Optic tract neuropathy complicating low-dose interferon treatment.

Optic neuritis occurred in three of our patients receiving treatment with alpha interferon-2b (Intron-A; 3MU thrice weekly) for chronic hepatitis. The complication appeared within, 1, 9 1/2 and 10 months of treatment, respectively. In all cases, blurred vision was the initial complaint and subsequent electrophysiologic investigation confirmed the presence of optic tract neuropathy. The patients had no other neurologic signs. Computerized tomography and magnetic resonance image of the brain were not remarkable. Psychiatric symptoms, in the form of an interferon-associated depressive reaction, were present in two of them; in one case, it was severe enough to require immediate discontinuation of treatment. In two patients the visual symptoms resolved and the parameters of neurophysiologic testing returned to normal within 1 month after stopping interferon. In one case, however, residual optic tract impairment associated with a unilateral central scotoma and a substantial decrease of visual acuity was present 2 years later, despite a course of methylprednizolone. In this patient the interferon treatment was continued for 3 months despite the visual symptoms, and he later received two additional interferon courses because of relapses of hepatitis. We conclude that clinically evident optic tract neuropathy may complicate interferon administration. Candidates for interferon treatment may need routine examination of optic fields and visual evoked potentials, before and during administration of the drug to avoid possibly permanent visual sequelae.

Adult↗