Antiviral drug

Oral Nucleoside/Nucleotide Analogs Without Hepatitis B Immune Globulin After Liver Transplantation for Hepatitis B.

Posted by

0


OBJECTIVES:

The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.

METHODS:

A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.

RESULTS:

Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.

CONCLUSIONS:

Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

Source: Nature

Double-Dose Tamiflu No Better Than Standard Dose for Severe Flu.

Posted by

0


 

A double dose of oseltamivir (Tamiflu) offers no advantage over single-dose therapy among children and adults with severe influenza, according to a BMJ study.

Some 325 patients (three-quarters children) hospitalized with severe flu in Southeast Asia were randomized to either double-dose oseltamivir (150 mg twice daily, or pediatric equivalent) or standard treatment (75 mg twice daily, or equivalent). Detected viruses included various subtypes of seasonal influenza, 2009 pandemic flu, and avian flu.

The proportion of patients with no detectable viral RNA on day 5 did not differ between the groups (roughly 70%). In addition, the groups did not differ with respect to clinical failure or in-hospital mortality. Findings generally were consistent regardless of patient age or flu type.

The authors say their results “do not support routine use” of double-dose therapy in severe flu. Editorialists agree, adding that the results “could help to preserve oseltamivir stocks during a future pandemic.”

Source: BMJ

Renal Safety of Treatment for Chronic HBV Infection.

Posted by

0


Nephrotoxicity was similar with tenofovir or entecavir.

Both tenofovir and entecavir are considered first-line oral antiviral agents for chronic hepatitis B virus (HBV) infection. In previous studies, nephrotoxicity has been observed with tenofovir therapy in patients coinfected with HBV and HIV. However, whether similar renal toxicity is present during tenofovir therapy in patients with HBV monoinfection is unclear.

This community-based, retrospective study compared nephrotoxicity in 80 patients with HBV infection who were treated with tenofovir (300 mg with varying frequency) — alone or in combination with another antiviral — and in 80 age- and sex-matched patients treated with entecavir alone (0.5 mg or 1 mg with varying frequency). Nephrotoxicity was defined as an incidence of serum creatinine (SCr) 2.5 mg/dL, an increase in SCr of 0.2 mg/dL, a drop in the estimated glomerular filtration rate (eGFR) to <60 mL/min, or an adjustment in medication dosage. The tenofovir and entecavir groups were similar in proportions of patients with diabetes mellitus (20% in each group), history of kidney or liver transplant (20% and 16%), and preexisting renal insufficiency (19% and 13%).

During treatment (mean duration, 80 weeks with tenofovir and 111 weeks with entecavir), more patients in the tenofovir versus the entecavir group had an eGFR <60 mL/min (15 vs. 6; P=0.022) and required medication dose adjustment (13 vs. 4; P=0.021). However, more patients in the entecavir versus the tenofovir group developed a SCr 2.5 mg/dL (6 vs. 1; P=0.053). Of note, in multivariate analysis, therapy assignment was not associated with an increase in SCr of 0.2 mg/dL or in eGFR <60 mL/min. Only history of organ transplant and preexisting renal insufficiency were associated with an increase in SCr of 0.2 mg/dL.

Comment: Renal adverse events were similar in patients receiving either tenofovir or entecavir for treatment of HBV infection. These findings are similar to those of long-term safety studies for both agents based on the treatment cohorts in their phase III registration trials. Clinicians should keep in mind that other patient factors, such as preexisting renal insufficiency, also increase the risk for renal adverse events.

Source: Journal Watch Gastroenterology

 

Antiviral Therapy Safely Stopped in HBeAg-Negative Patients with Hepatitis B Infection.

Posted by

0


Discontinuing adefovir did not lead to any adverse events during 5.5 years of follow-up.

Although oral antiviral agents are effective in suppressing hepatitis B virus (HBV) in hepatitis B e antigen (HBeAg)-negative patients, it is unclear if therapy can ever be stopped. Previous studies observed that viral relapse occurred universally after a short course of treatment (J Gastroenterol Hepatol 2011; 26:456). Long-term suppressive therapy may afford an opportunity to eventually stop treatment.

In this observational study, a group of 33 well-characterized HBeAg-negative patients with HBV infection who had been receiving suppressive therapy with adefovir (10 mg daily) for 4 to 5 years discontinued treatment. Patients were then followed for 5.5 years, with measurement of serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA every 3 to 6 months to assess for relapse of HBV infection.

During a median follow-up of 69 months, 18 of 33 patients (55%) maintained persistently normal ALT and undetectable viral load (HBV DNA <29 IU/mL). Of these 18 responders, 13 (72%) cleared HBsAg, and 9 of the 13 (69%) seroconverted to hepatitis B surface antibody (HBsAb). No adverse events occurred, and in the 45% of patients who relapsed, an oral antiviral agent was safely restarted.

Comment: This long-term, prospective cohort study of a small group of HBeAg-negative patients with hepatitis B infection suggests that patients whose viral loads are suppressed with an oral agent for 4 to 5 years can safely discontinue antiviral therapy. Moreover, about half will not experience viral relapse, and the majority of these patients will develop HBsAb. However, stopping therapy should be considered only in highly compliant patients without cirrhosis. In patients with cirrhosis, close monitoring is necessary, and viral relapse can lead to hepatic decompensation.

Souurce: Journal Watch Gastroenterology