Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin (anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia. METHODS: Ninety-three consecutive patients (62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed. RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia (19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia (70.0% vs 34.9%, P=0.030), lower EPO concentrations (median 16.35 vs 30.65 mU/mL, P=0.005), and higher HCV RNA viral load (median 891.5X103 vs 367.5X103 IU/mL, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia (adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients (P=0.001). CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-naive HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.

A Giant Renal Vein Aneurysm in a Patient with Liver Cirrhosis.

We present an unusual case of a 40-year-old female patient with liver cirrhosis and diffuse abdominal pain. The imaging studies revealed a huge renal vein aneurysm. The patient refused any interventional management, despite the risk of possible rupture, and after a week of mild pain therapy, she was discharged. She was followed up closely, and after one year, she remains asymptomatic. Conservative management of such patients has been described before with success. However, open repair or percutaneous thrombosis of the aneurysm remains the indicated therapy, when vein patency is an issue for organ viability.

Listeria monocytogenes peritonitis: presentation, clinical features, treatment, and outcome.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication in cirrhotic patients. Gram (-) (E. coli, Klebsiella pneumoniae), and Gram (+) (Streptococci, Staphylococci) bacteria are most frequently cultured from patients'ascites. Listeria monocytogenes (Lm) is scarcely reported as a causative agent. OBJECTIVE: Our objective is to describe Lm peritonitis as a clinical entity, including its presentation, clinical features, treatment, and the potential factors that might affect survival outcome. DATA SOURCES: MEDLINE, Scholar.Google, Scopus databases, including English, Spanish, French, and German language papers published between 1966 and June 2011, and reference lists. DATA EXTRACTION: investigators abstracted details about medical history, disease presentation, laboratory data, treatment and outcome. DATA SYNTHESIS: One-hundred and twenty-eight cases with known survival outcome--eighty-six cirrhotics, seventeen individuals undergoing continuous ambulatory peritoneal dialysis and another twenty-five with other or no underline condition were reviewed. An additional number of twenty-five cases with unknown outcome were searched in Listeria studies published from 1990 to 2009 and were only used for calculating worldwide distribution. CONCLUSION: Cirrhotics, mostly alcoholics, presented with fever and abdominal pain. Those who succumbed had significantly higher peripheral WBC count (15622 vs. 8155 cells/mm(3), p = 0.01) and (%) polymorphonuclear cells in differential count (83.3 vs. 71%, p = 0.001). Higher mortality was experienced in those with comorbidities, and those who presented with encephalopathy. Lower mortality was experienced in patients on continuous ambulatory peritoneal dialysis. Ascites was neutrocytic in 86% of the samples. In the sum of the cases mortality was 27.3%, with significantly highest rates in the elderly, in patients with bacteremia, immunosuppression, hematological malignancies, and lowest rates in those who presented with abdominal pain and in diabetics (type I or II). The latter observation was surprising and could be considered a single fortuitous fact. Initial appropriate treatment was associated with significantly better outcome (p = 0.002) than inappropriate; combination therapy with an aminoglycoside was superior to monotherapy (p = 0.038).

Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter?

Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4.

Hepatitis C virus genotyping in Greece: unexpected high prevalence of genotype 5a in a Greek island.

Hepatitis C virus (HCV) genotype 5 (G5) is a rare genotype reported mainly in South Africa. However, increasing data suggest the sporadic presence of this genotype in different European countries. To assess the epidemiology of HCV-G5 in Greece, genotyping was performed in 973 consecutive patients infected with HCV, referred to 7 hepatology centers throughout Greece, from January 2005 to December 2009. Genotype 5a (19 patients, 1.9%) was the fifth most prevalent genotype after genotype 1 (408 patients, 41.9%), genotype 3 (318 patients, 32.7%), genotype 4 (158 patients, 16.2%), and genotype 2 (70 patients, 7.2%). The majority of patients infected with G5 (16/19,84.2%) were referred to the General Hospital of Rhodes, an island in south-east Greece. The HCV genotype distribution in that particular island, indicates a particularly high G5 prevalence of 12.8%, after genotype 1 (40%), genotype 3 (28%), and genotype 4 (15%). Among the patients from Rhodes infected with G5 (n = 16), 13 (81.2%) were females. The mean age was 62.3 ± 6.5 years, significantly older than the patients infected with other HCV genotypes (mean age 40.6 ± 7.2, P < 0.0001). Nine out of the 16 cases (56.2%) presented features of high pre-treatment viral loads. Advanced liver fibrosis (Metavir F3-F4) was found in four out of five performed liver biopsies. Ten patients received treatment with pegylated interferon plus ribavirin and a sustained viral response were achieved in six cases. The source of infection is unknown but parenteral iatrogenic routes of transmission seem to have contributed significantly to the spread of genotype 5a in this region.

Long-term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg-negative chronic hepatitis B patients.

BACKGROUND/AIMS: As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy. METHODS: Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eC(CR) ) and compared with a matched control group of untreated inactive hepatitis B virus carriers. RESULTS: Serum HBV DNA became undetectable in 39 (85%) patients after a mean of 37 ± 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eC(CR) (95 ± 31-83 ± 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeC(CR) decrease >30%. Similar changes in eC(CR) were observed in the control group (108 ± 28-96 ± 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eC(CR) were independent predictors of eC(CR) reduction. CONCLUSIONS: Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function.

Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study.

OBJECTIVE: To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy. DESIGN: Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective-prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months. SETTING: A nationwide network of liver centres. PATIENTS: 818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity. INTERVENTIONS: All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy. MAIN OUTCOME MEASURES: Development of HCC. RESULTS: During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50-60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission. CONCLUSIONS: Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC.

Pegylated interferon alfa-2b pen device and ribavirin treatment for patients with chronic hepatitis C: an evaluation of patient satisfaction.

OBJECTIVE: The aim of this study was to evaluate the satisfaction of patients with chronic hepatitis C who used the pegylated interferon α-2b pen device. METHODS: Patients from multiple centers in Greece were recruited to participate in this noninterventional, observational study. Patients received pen device training for at least 6 weeks before treatment and used questionnaires to provide feedback (rating scale: 1-4, negative; 5-7, positive) on training, medication preparation and injection, and appreciation of the device. Results were analyzed with standard statistical analysis and multivariate logistic regression. RESULTS: In total, 507 patients (mean age, 43.5 years), 77.4% of whom were treatment naive, participated in the study. Overall, 84.2% of patients rated training positively, 67.4% of patients rated medication preparation positively, and 88.3% of patients rated medication injection positively. Appreciation of the pen device treatment method was rated positively by 82.2% of patients. Intravenous drug users were more likely to rate medication injection positively (P=0.0284) and to appreciate this method of drug delivery (P=0.0328) than other patients. Patients with lower levels of education were less likely to rate training positively (P=0.0202) and showed less appreciation for this route of drug delivery (P=0.0341) than other patients. Treatment-naive patients were more likely to provide positive responses about the overall procedure than were treatment-experienced patients (odds ratio: 1.932; P=0.032). Adverse events were reported by 6.4% (29 of 453) of patients. CONCLUSION: Patients were satisfied with the pegylated interferon α-2b pen device; therefore, good treatment adherence is expected with its use.

Possible green tea-induced thrombotic thrombocytopenic purpura.

PURPOSE: A case of a patient who developed thrombotic thrombocytopenic purpura (TTP) after consuming a weight-loss product containing green tea is reported. SUMMARY: A 38-year-old, 68-kg Caucasian woman arrived at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. She had no symptoms of infection and denied illegal drug use. Her medical history included hypothyroidism, for which she was treated with levothyroxine 150 microg daily for the past four years. She reported that she had been using a green tea preparation for the two months before admission to lose body weight. The daily preparation contained 200 mg of green tea extract 5:1, equivalent to 1 g of natural green tea. On clinical examination, the patient appeared acutely ill and was afebrile, with pallor, petechiae, and purpura of the extremities. Laboratory test results at the time of admission revealed that the patient had anemia and marked thrombocytopenia. A peripheral blood smear demonstrated a feature of microangiopathic hemolytic anemia. Immunoglobulin G autoantibodies against ADAM metallopeptidase with thrombospondin type 1 motif, 13 were detected. On hospital day 3, the patient appeared confused and exhibited aphasia that was initially transient but then recurrent. Brain computerized tomography did not exhibit focal pathology. Over the next few days, her neurologic symptoms subsided and her platelet count and hematocrit value gradually increased. Plasmapheresis was performed (12 procedures). Corticosteroid treatment was also initiated. After 20 days of hospitalization, the patient was discharged. CONCLUSION: A 38-year-old woman developed TTP after consuming a weight-loss product containing green tea extract for two months.

Hepatic parenchyma resection using stapling devices: peri-operative and long-term outcome.

BACKGROUND: Stapler-assisted hepatectomy has not been well established, as a routine procedure, although few reports exist in the literature. This analysis assesses the safety and outcome of the method based on peri-operative data. MATERIALS AND METHODS: From February 2005 to December 2006, endo GIA vascular staplers were used for parenchymal liver transection in 62 consecutive cases in our department. There were 18 (29%) patients with hepatocellular carcinoma (HCC), 31 (50%) with metastatic lesions and 13 (21%) with benign lesions [adenoma, focal nodular hyperplasia (FNH), simple cysts]. Twenty-one patients underwent major resections (33.9%) (i.e. removal of three segments or more) and 41 (66.1%) minor hepatic resections. RESULTS: Median blood loss was 260 ml. The median total operative time was 150 min and median transection time was 35 min. No patient required more than 2 days of intensive care unit (ICU) treatment. The median hospital stay was 8 days. Surgical complications included two (3%) cases of bile leak, two (3%) cases of pneumonia, two (3%) cases with wound infection and two (3%) cases with pleural effusion. The peri-operative mortality was zero. In a 30-month median follow-up, all patients with benign lesions were alive and free of disease. The 3-year disease-free survival for patients with HCC was 61% (57% for patients with colorectal metastases) and the 3-year survival 72% (68% for patients with colorectal metastases). CONCLUSION: Stapler-assisted liver resection is feasible with a low incidence of surgical complications. It can be used as an alternative for parenchyma transection especially in demanding hepatectomies for elimination of the operating time and control of bleeding.

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.

Cytokeratin 8 and 18 expression in imprint smears of chronic viral hepatitis, autoimmune hepatitis and hepatocellular carcinoma. A preliminary study.

OBJECTIVE: To investigate whether the expression of cytokeratin (CK) 8 and 18 is altered in chronic active viral hepatitis, autoimmune hepatitis and hepatocellular carcinoma. STUDY DESIGN: Cytologic imprint smears were obtained from 53 liver core biopsy specimens and were studied immunocytochemically for the expression of CK8 and 18. RESULTS: CK8-positive expression was observed in 45.5% of chronic active hepatitis B (CH-B), 20% of chronic active hepatitis C (CH-C), 90% of autoimmune hepatitis (AIH) and 83.3% of hepatocellular carcinoma (HCC) cases. CK18-positive expression was observed in 36.4% of CH-B, 26.7% of CH-C, 70% of AIH and 83.3% of HCC cases. A statistically significant association was found between CK8- and CK18-positive expression and the diagnosis of AIH and HCC. In contrast, CH-C and CH-B were associated with negative CK8 and CK18 expression. In addition, a negative [CK8(-)/CK18(-)] or imbalanced [CK8(-)/CK18(+), CK8(+)/CK18(-)] expression pattern was found in 100.0% and 81.18% of CH-C and CH-B cases, respectively, while the relative percentages of AIH and HCC cases were significantly lower (30.0% and 16.7%, respectively) (p < 0.0001). CONCLUSION: Our results indicate that CK8 and 18 expression is maintained in AIH and HCC and altered in CH-B and CH-C. The pathogenetic mechanism of this alteration remains to be clarified.

Hepatitis C virus survival curve analysis in naïve patients treated with peginterferon alpha-2b plus ribavirin. A randomized controlled trial for induction with high doses of peginterferon and predictability of sustained viral response from early virologic data.

AIM: To evaluate the significance of induction with high doses of pegylated interferon -2b (Peg-IFNalpha-2b) and the predictability of sustained virologic response (SVR) in naïve patients with chronic hepatitis C. METHODS: 188 consecutive naïve patients with chronic hepatitis C were enrolled in a randomised controlled clinical trial. Patients were randomised to receive either Peg-IFN -2b 3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800-1200 mg ribavirin (Arm A) or Peg-IFNalpha-2b 1.5 mcg/kg QW x 48 weeks plus 800-1200 mg ribavirin (Arm B). HCV-RNA was obtained at 0, 4, 8, 12, 16, 24, 48 and 72 weeks. Differences between schemes were evaluated by Kaplan-Meier curves. Predictability of SVR was assessed by two-way contingency table analysis and ROC curve analysis. RESULTS: From 176 patients, 75 had genotype 1, 15 genotype 2, 75 genotype 3 and 11 genotype 4. No statistical significance emerged in HCV-RNA positivity, side effects and withdrawals between schemes. Patients with genotype 1 achieved lower SVR (46.6%) in comparison to patients with genotypes 2/3 (94.1%, p < 0.001) and 4 (90.9%, p = 0.002). The most appropriate time for estimation of SVR for genotype 1 is week 8 (accuracy = 0.84, AUC = 0.90) while predictability increases with time in genotypes 2/3, reaching maximum accuracy = 0.93 and AUC = 0.76 at week 16. CONCLUSION: Induction with high doses of Peg-IFNalpha-2b does not preclude better outcome and rapid virologic response at 4 weeks of treatment sufficiently predicts SVR. These findings might be useful in an attempt to gain supportive evidence for decision making in difficult-to-treat patients.

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 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.

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.

Extensive psoriasis induced by pegylated interferon alpha-2b treatment for chronic hepatitis B.

A 32-year-old man with chronic hepatitis B who was treated with pegylated interferon alpha-2b once a week, developed widespread psoriasis 4 weeks after the beginning of the treatment. There was no history of psoriasis. The treatment was stopped and gradually the eruption vanished. Thereafter, the patient was treated with lamivudine successfully without dermatological or other sequelae.