Genotype 4 HCV infection is difficult to cure with pegylated interferon and ribavirin. Results from a Greek Nationwide Cohort Study.

BACKGROUND AND AIM: Patients with genotype 4 (G4) chronic hepatitis C (CHC) are considered a difficult to treat population, although current data on G4 treatment responsiveness and duration are controversial. Greece represents a country with an intermediate prevalence of G4 infections, offering an opportunity to compare treatment outcomes by genotype and to identify potential prognostic factors for sustained virologic response (SVR). METHODS: All CHC patients from the HepNet.Greece, an ongoing nationwide cohort study on viral hepatitis, with known hepatitis C virus (HCV) genotype who received treatment with Peg-IFNa and ribavirin were analyzed. RESULTS: From 4443 patients, 951 (61.7% males, 78.4% Greeks, median age 40.6 years, 10% cirrhosis) fulfilled the inclusion criteria. G4 was found in 125 (13.1%) patients. Genotype distribution was not significantly different between Greeks and immigrants. Patients with G4 had similar odds of SVR compared to G1 but significantly lower compared to G2/G3. Age, treatment discontinuation, presence of cirrhosis and previous history of HCV-treatment were associated with lower probabilities of SVR. Ethnicity did not affect SVR for all genotypes while response to treatment was similar between Greek and Egyptian patients groups (35.7% vs 40.9%, p=0.660%) with G4 infection. The relation between SVR and genotype did not substantially change after adjustment for age, gender, cirrhosis, treatment interruption and history of HCV-treatment. CONCLUSIONS: The findings of this large cohort of CHC patients with a well balanced genotype distribution further supports the idea of considering G4 as a difficult to treat genotype. Further investigation is needed to identify genotype specific prognostic factors.

Severe eosinophilic infiltration in colonic biopsies predicts patients with ulcerative colitis not responding to medical therapy.

AIM: Eosinophils are potent proinflammatory cells that are involved in the pathogenesis of ulcerative colitis (UC). We evaluated the infiltration of eosinophils into the lamina propria in patients with active and inactive ulcerative colitis (UC) and investigated its clinical significance, among other variables, in predicting the outcome of medical treatment in active disease. METHOD: We studied colorectal biopsy specimens from 18 UC patients with disease in long-standing remission, from 22 patients with active disease who responded to therapy (12 with complete response and 10 with partial response) and from 10 patients who were nonresponders. Demographic information was obtained at baseline, and clinical, endoscopic and laboratory data were obtained at baseline and 12 weeks post-treatment. We evaluated five histological features: mucosal ulceration; mucosal erosions; crypt abscesses; cryptitis; and eosinophilic infiltration of the lamina propria. The severity of these lesions was graded as: none or minimal; mild; moderate; or severe. Statistical analyses were performed between responders and nonresponders for differences in demographic, clinical, laboratory, endoscopic and histological parameters. RESULTS: Laboratory, endoscopic and histological parameters were significantly improved after treatment only in the complete responders group. Analyses of baseline data revealed no significant differences in parameters between complete or partial responders and nonresponders, except for a less severe eosinophilic infiltration of lamina propria in complete responders (P < 0.05). Multiple logistic regression analysis showed that severe eosinophilic infiltration in colonic biopsies was the most significant predictor of poor response to medical therapy. CONCLUSION: Assessing the severity of eosinophilic infiltration in the lamina propria of colonic biopsies in patients with ulcerative colitis could be a valuable predictive tool of response to medical therapy.

Inhibition of TNFalpha does not induce viral reactivation in patients with chronic hepatitis C infection: two cases.

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.

Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study.

BACKGROUND: Heparin could be beneficial to the treatment of active ulcerative colitis because of its anticoagulant, anti-inflammatory and immunomodulatory properties. AIM: To evaluate the tolerability, safety and efficacy of low-molecular-weight heparin as adjuvant therapy in patients with active ulcerative colitis. METHODS: Thirty-four adult patients with active ulcerative colitis were consecutively included in a prospective, randomized, comparative study, and were treated for 12 weeks. Eighteen patients in the 'standard therapy' group were treated with aminosalicylates and weekly tapered corticosteroids. Sixteen patients in the 'heparin therapy' group were treated with standard therapy plus enoxaparin 100 Anti-Xa IU/kg/day subcutaneously. RESULTS: Seventeen patients in the 'standard therapy' group and 15 patients in the 'heparin therapy' group completed the study. Tolerability and compliance to therapy were excellent and no withdrawals were noted because of complications. There was a significant improvement in the disease severity in both groups (P<0.001), without any difference between them (P=not significant). Both treatment groups showed similar proportions of disease improvement (65% and 73%, respectively; P=not significant). There were no significant differences in inflammation (fibrinogen, ESR, CRP) and coagulation (thrombin-antithrombin complex, F1+2, D-dimers) parameters during and at the end of the study between treatment groups. CONCLUSION: Adjuvant administration of low-molecular heparin in patients with active ulcerative colitis is safe and well tolerated, but no additive benefit over standard therapy for ulcerative colitis was noted.

Adefovir dipivoxil added to ongoing lamivudine therapy in patients with lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND: Long-term treatment with lamivudine is required to control viral replication in patients with hepatitis B e antigen-negative chronic hepatitis B, but is associated with a high rate of viral resistance. The role of adefovir dipivoxil in these patients has not been definitively evaluated. AIM: To address the role of adefovir in the management of patients with lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B. METHODS: Patients were assigned to receive adefovir 10 mg once daily plus ongoing lamivudine 100 mg once daily for 52 weeks. The primary end point was reduction in serum hepatitis B virus DNA level (hepatitis B virus DNA response). Secondary end points included the proportion of patients with undetectable hepatitis B virus DNA at week 52 (complete virological response) and the percentage of patients with normalization of alanine transferase level at week 52 (biochemical response). RESULTS: A total of 49 consecutive patients were enrolled in this study. After 52 weeks of treatment, all patients had an hepatitis B virus DNA response and 57.1% had complete virological response. Biochemical response occurred in 75.6% of patients. CONCLUSIONS: Administration of adefovir in patients with lamivudine-resistant chronic hepatitis B results in significant suppression of viral replication. Nevertheless, continuous therapy will probably be needed in order to maintain remission in these patients.

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 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.