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EASL 2014: Long-term Tenofovir Maintains Viral Suppression in People with Hepatitis B


Treatment with tenofovir (Viread) for 3 years remained effective in keeping hepatitis B virus (HBV) suppressed, normalizing liver inflammation, and potentially reducing liver disease progression, according to studies from Germany, France, and Spain presented at the 49thEASL International Liver Congress (EASL 2014) recently held in London.

Over years or decades chronic hepatitis B infection can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma (HCC), a type of liver cancer. Hepatitis B treatment involves nucleoside/nucleotide antiviral drugs including tenofovir, entecavir (Baraclude), adefovir (Hepsera), and lamivudine (Epivir), which may be more effective when used with pegylated interferon.


Jorg Petersen of Asklepios Klinik St Georg in Hamburg presented findings from the German Multicenter Non-Interventional, or GEMINI, study.

This analysis included 400 chronic hepatitis B monoinfected patients starting tenofovir for the first time. About 70% were men, the average age was 44 years, and about 30% were hepatitis B "e" antigen (HBeAg) positive. Half had not previously received hepatitis B treatment and 11% had cirrhosis. People with HIV or hepatitis B were excluded.

After 3 years on treatment, virological response rates were 90% for treatment-naive HBeAg positive patients, 89% for treatment-experienced HBeAg positive patients, 92% for treatment-naive HBeAg negative patients, and 99% for treatment-experienced HBeAg negative patients.

Among the few participants who experienced viral breakthrough during treatment, no tenofovir resistance mutations were detected. Among HBeAg positive participants, 6% achieved hepatitis B surface antigen (HBsAg) loss -- the closest thing to a virological cure -- as did 2% of HBeAg negative participants. Most patients experienced alanine aminotransferase (ALT) normalization, indicating reduced liver inflammation.

Treatment was generally safe and well-tolerated. The most common side effects were fatigue, headache, abdominal pain, and nausea. Kidney function biomarkers remained stable overall. The 5 participants with kidney-related adverse events had risk factors including older age, diabetes, hypertension, or pre-existing kidney impairment. 2 patients -- both with cirrhosis at baseline -- developed liver cancer. Among 7 women who became pregnant, all newborns were healthy.

"After 3 years in real-life practice [tenofovir] profoundly suppressed HBV replication in the majority of naive and pretreated patients irrespective of the previous medication," the researchers concluded.


Georges-Philippe Pageaux from CHU Saint-Eloi in Montpellier and colleagues presented findings from the French VIREAL study in 2 posters.

This analysis included 440 chronic hepatitis B patients who had not previously used tenofovir. Again, about 70% were men, the mean age was 45 years, and nearly 30% were HBeAg positive. 60% were treatment-experienced and one-third had either advanced fibrosis or cirrhosis.

After 3 years on tenofovir, virological response rates were 92% for HBeAg positive and 97% for HBeAg negative patients, and 94% for treatment-naive and 97% for previously treated participants. Within the latter group, those previously treated with lamivudine and adefovir did better than those who had previously used entecavir (99% vs 88%, respectively). 3 HBeAg positive and 9 HBeAg negative participants experienced HBsAg loss. Again, most experienced ALT normalization. 3 people developed hepatocellular carcinoma during follow-up, all of whom had cirrhosis at baseline.

Here too, treatment was generally well-tolerated with no major safety issues reported. The most common adverse events were weakness, abdominal pain, nausea, vomiting, and diarrhea. Kidney function (eGFR) remained stable.

"In real-life practice, 3 years of therapy with [tenofovir] were associated with high virological response both in treatment-naive and -experienced patients [and a] very low number of HCC cases," the investigators concluded,

This team also reported in a second poster that tenofovir was effective and generally well-tolerated in a subset of 48 "elderly" participants, many with comorbid conditions including diabetes and hypertension. Response rates were high and similar for elderly and younger patients (100% vs 95%, respectively). Two of the patients with HBsAg loss were age 65 or older. Kidney function was lower in older compared with younger participants, but remained stable over time in both subgroups.

"Long term [tenofovir]-treatment presented a favorable safety profile in younger and elderly patients with comorbidities such as hypertension and diabetes," the researchers concluded.


Finally, Maria Buti of Hospital Valle Hebron in Barcelona and colleagues presented data from the Spanish Chronic Hepatitis B Registry, or CIBERHEP.

This analysis included 370 chronic hepatitis B patients treated with tenofovir for a median of 2.2 years (85% as monotherapy). About 70% were men and the median age was 47 years. About half were treatment-naive and half previously treated. 27% of the treatment-naive patients and 22% of the treatment-experienced group were HBeAg positive, and 17% and 10%, respectively, had cirrhosis. People with HIV or hepatitis B coinfection were excluded.

After 1 year of therapy, 74% of HBeAg positive and 90% of HBeAg negative participants had undetectable HBV DNA viral load, with similar rates for treatment-naive and treatment-experienced patients. After about 4 years (192 weeks) on treatment, all participants in all subgroups had undetectable viral load.

Looking at serological response, 31% of treatment-naive patients and 16% of previously treated people experienced HBeAg loss. However, HBeAg loss remained stable in 29% and only 5%, respectively. 3 treatment-naive patients with HBeAg loss also achieved HBsAg loss, as did 1 HBeAg negative participant.

Again, treatment was generally well-tolerated and kidney function remained stable.

"Virological response was similar between naive and previously treated patients," the researchers concluded. "However, HBeAg loss was more frequent and stable in [the] naive group."



J Petersen, R Heyne, S Mauss, et al (GEMINIS). Effectiveness of tenofovir DF for chronic hepatitis B in field practice -- 3 year final results from the prospective German Multicenter Non-Interventional Study. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract O122.

G-PPageaux, F Zoulim, X Causse, et al (VIREAL Group).Long-term treatment with tenofovir in treatment-naive or -experienced CHB patients is effective and well tolerated in real-life practice: 3 years results of the VIREAL study. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P1061.

X Causse, G-PPageaux, F Zoulim(VIREAL Group. 3-year treatment with tenofovir in real-life is effective and well tolerated in CHB patients, including the elderly and patients with comorbidities. 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P1062.

D Tabernero, JM Sánchez-Tapias, JL Calleja, et al (CIBERHEP). Long-term efficacy of tenofovir in previously treated and naive patients. results from the Spanish chronic hepatitis B registry (CIBERHEP). 49thEuropean Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P1058.