Pierre Pradat

Entecavir treatment for chronic hepatitis B: Adaptation is not needed for the majority of naïve patients with a partial virological response†‡

Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)‐naïve chronic hepatitis B (CHB) patients. The aim of this study was to investigate the long term efficacy and safety of ETV in NA‐naïve CHB patients, particularly in those with detectable hepatitis B virus (HBV) DNA after 48 weeks, in whom treatment adaptation is suggested by current guidelines. In a multicenter cohort study, we investigated 333 CHB patients treated with entecavir monotherapy. The NA‐naïve population consisted of 243 patients, whereas 90 were NA‐experienced. Virological response (VR) (HBV DNA <80 IU/mL) was achieved in 48%, 76%, and 90% of hepatitis B e antigen (HBeAg)‐positive and in 89%, 98%, and 99% of HBeAg‐negative NA‐naïve patients at weeks 48, 96, and 144, respectively. Thirty‐six of 175 (21%) NA‐naïve patients with at least 48 weeks of follow‐up had a detectable load at week 48 (partial virological response [PVR]). Twenty‐nine (81%) patients with PVR reached VR during prolonged ETV monotherapy, and none of them developed ETV‐resistance. Among 22 patients with HBV DNA <1,000 IU/mL at week 48, VR was achieved in 21 (95%) patients, compared with eight of 14 (57%) patients with HBV DNA ≥1,000 IU/mL. Continuous HBV DNA decline was observed in most patients without VR during follow‐up, and in three patients adherence was suboptimal according to the treating physician. ETV was safe and did not affect renal function or cause lactic acidosis. Conclusion: ETV monotherapy can be continued in NA‐naïve patients with detectable HBV DNA at week 48, particularly in those with a low viral load because long‐term ETV leads to a virological response in the vast majority of patients. (HEPATOLOGY 2011;)

Ribavirin at the Era of Novel Direct Antiviral Agents for the Treatment of Hepatitis C Virus Infection: Relevance of Pharmacological Monitoring

Ribavirin is often used for the treatment of hepatitis C virus (HCV) infection. Although its mechanisms of action remain to be clearly elucidated, ribavirin plays a beneficial role for achieving virological response and decreasing the rate of virological relapse after treatment cessation. However, ribavirin may induce side effects leading to early treatment discontinuation. Among them, hemolytic anemia is the most frequent and results from intraerythrocyte accumulation. Pharmacological studies have shown that early ribavirin exposure assessed by the area under the curve (AUC) at day 0 and ribavirin trough concentration during the first three months of therapy were correlated with sustained virological response (SVR). These studies highlighted the relevance of ribavirin pharmacologic monitoring and early dose adaptation during therapy. Although the role of ribavirin within new direct acting antiviral (DAA) combinations will probably decrease in the future, its potential benefit in difficult-to-treat patients such as patients with severe hepatopathy or patients who failed triple therapy including patients with multiresistance will need to be further investigated.

Hepatitis C: CIFN for re-treatment of PEG-IFN plus RBV nonresponders?

The current re-treatment options available to patients with chronic hepatitis C who fail to respond to treatment with pegylated interferon plus ribavirin are limited. Findings from a large, multicenter study suggest that re-treatment with consensus interferon plus ribavirin should now be considered for compliant, motivated nonresponders.

760 ENTECAVIR TREATMENT IS EFFECTIVE IN PATIENTS WITH PREVIOUS ADEFOVIR TREATMENT: RESULTS FROM AN INTERNATIONAL MULTICENTER COHORT STUDY

Total bilirubin (mmol/L) 20–30 ULN >30–40 ULN >40 ULN Creatinine (mmol/L) Normal >1.0–1.1 ULN >1.1–1.2 ULN >1.2–1.3 ULN >1.3 ULN Activity of PT (%) >40 30– 0–40 >40–80 >80 >80+ one or both side pleural fluid Infection (depend on WBC 109/L) Normal WBC >10–15 or N >70– 15–20 or N >80– 20 or N >90% Inflammation manifestion of lung