High treatment modification rates with lamivudine therapy in HBV-infected patients with low baseline viremia and early virological response: A multicenter study.

OBJECTIVE: Low baseline viremia and an early treatment response predict the best outcomes in hepatitis B virus (HBV)-infected patients treated with nucleoside analogues with low barriers to resistance. The aim of this study was to assess the long-term results and effectiveness of lamivudine in patients with low baseline viremia and early virological treatment response. METHODS: In this multicenter, real-life setting study, 111 antiviral-naive patients with low baseline viremia (HBV DNA <10(7) copies/mL) plus an early virological response (HBV DNA <300 copies/mL at week 24) treated with lamivudine were enrolled. The primary end-point was treatment failure, defined as the re-emergence of detectable viremia or at least a 1 log increase in HBV DNA, resulting in a titer of ≥ 300 copies/mL with lamivudine treatment after week 24, which required treatment modification. RESULTS: Altogether 111 patients, including 78 non-cirrhotic and 33 cirrhotic patients, were included in the study. Treatment failure occurred in 30.8% of the non-cirrhotic patients over a median follow-up period of 32.5 months, and the 1-, 2-, 3-, 4- and 5-year treatment failure rates were 6.5%, 14.0%, 31.4%, 39.6% and 43.1%, respectively. Treatment failure occurred in 28.8% of the whole group. There were no differences between the cirrhotic and non-cirrhotic patients. CONCLUSIONS: Lamivudine treatment had a high treatment modification rate in patients with low baseline viremia and early virological response over a long-term follow-up in a real-life setting. The pretreatment and on-treatment favorable characteristics found in the studies with telbivudine appeared to be inapplicable to lamivudine.

Partial virological response to three different nucleotide analogues in naive patients with chronic hepatitis B.

BACKGROUND: The definition of partial virological response (PVR) was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues (NA) is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir monotherapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS: We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July 2013. RESULTS: Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 (6-147) months. PVR rates at 24 weeks were similar among three NAs (lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P=0.981). For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough (VBR) for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR (HR: 3.09; 95% CI: 1.09-8.74; P=0.034); also lamivudine treated patients older than 50 years seemed to have a tendency for VBR (HR: 2.80; 95% CI: 0.99-8.18; P=0.052). A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations. CONCLUSIONS: Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.

Prognostic implication of serum vascular endothelial growth factor in advanced hepatocellular carcinoma staging.

BACKGROUND: Staging systems have considerable impact on hepatocellular carcinoma (HCC) treatment approaches and outcomes. There is an unmet need to improve their stratification ability. We have evaluated four commonly used staging systems and assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF) could improve their prognostic stratification. MATERIAL AND METHODS: Four staging systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh were evaluated in 78 HCC patients; their stratification abilities were detected by Kaplan-Meier curves and log-rank test; their accuracies of predicting survival were compared with the concordance index. Serum VEGF levels were measured using ELISA method. Recursive partitioning was used to determine the optimal VEGF cutoff. The prognostic significance of VEGF cutoff and other parameters were analyzed using univariate and multivariate models. RESULTS: None of the staging systems demonstrated better discriminatory ability in predicting survival. The four staging systems did not reveal significant differences in probability of survival across their intermediate-advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were identified as the independent prognostic factors. Survival comparison with high and low VEGF levels was significant for advanced HCC, while insignificant for early disease. CONCLUSION: Staging systems with conventional parameters did not provide good prognostic stratification for survival in advanced HCC population. Serum VEGF level was an independent predictor of survival in advanced HCC, and provided more survival homogeneity within the advanced stages of conventional staging systems.

Activity and damage in granulomatosis with polyangiitis.

AIM: To retrospectively analyze disease activity and damage-associated factors in granulomatosis with polyangiitis (GPA) in Turkey. METHOD: A retrospective analysis was carried out in 21 GPA patients. Assessments for activity were performed with the Birmingham Vasculitis Activity Score for GPA (BVAS/GPA) and for permanent organ damage by the Vasculitis Damage Index (VDI). RESULTS: Lower BVAS/GPA (P = 0.002), absence of renal involvement (P = 0.003) and higher creatinine clearence (P = 0.000) at diagnosis increased the likelihood of achieving remission at 6 weeks. Relapses were associated with high creatinine clearence (P = 0.021), low BVAS/GPA (P = 0.014), absence of renal involvement (P = 0.036) and proteinuria (< 0.5/24 h) (P = 0.013) at diagnosis, whereas achieving remission at 6 weeks (P = 0.012) was associated with absence of co-trimoxazole usage (P = 0.038) and less severe clinical subgroup (P = 0.034). Lower cumulative first 6 months of cyclophosphamide and methylprednisolone were associated with earlier (≤ 12 months) relapses (P = 0.048 and P = 0.083, respectively). Baseline damage (VDI ≥ 1) was associated with a delay in diagnosis (P = 0.032), presentation with milder clinical subgroups (P = 0.052) and low serum creatinine (P = 0.013). The increase in VDI in the first 12 months (early damage) constituted most (91%) of the total damage measured at the end of follow-up. CONCLUSIONS: Despite high early remission rates, relapse represents a major problem in localized GPA in our study. Baseline damage was associated with longer diagnostic delay and lower baseline serum creatinine. The initial phase of the disease seems to be the most crucial period for mortality and accumulated damage.