SUMMARY: Tenofovir (Viread) produced good hepatitis B virus (HBV) suppression in both nucleoside/nucleotide-naive and treatment-experienced patients in routine clinical practice, indicating that clinical trial outcomes extend to real life, according to findings presented the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. Furthermore, most tenofovir recipients did not show evidence of kidney toxicity, even in the absence of formal screening and exclusion of at-risk patients.

By Liz Highleyman

Pietro Lampertico from Universita degli Studi di Milano and colleagues conducted a retrospective/prospective cohort study that enrolled 737 chronic hepatitis B patients starting tenofovir at 17 centers in Italy.

Three-quarters were men, the median age was 56 years, and 77% were hepatitis B "e" antigen (HBeAg) negative. Individuals with HIV coinfection were excluded. About 40% had liver cirrhosis and 9% had hepatocellular carcinoma.

Participants could be on either tenofovir monotherapy (27%) or combination therapy (72%), mostly with lamivudine (Epivir-HBV). Nearly one-third (30%) had received prior interferon treatment and 71% had previously used nucleoside/nucleotide analogs or showed resistance to these drugs; the remaining 29% were nucleoside/nucleotide-naive. 14% of patients started on a lower tenofovir dose due to reduced creatinine clearance, a sign of impaired kidney function.

Patients were followed for a median of 16 months (range 0-52 months). The researchers measured HBV DNA viral load and looked for adverse events, focusing on kidney dysfunction, since tenofovir is known to cause kidney impairment in a small proportion of patients.

Results

	Among nucleoside/nucleotide-naive patients (median baseline viral load of 5.9 log IU/mL), rates of virological response, or undetectable HBV DNA, were as follows:
	12 weeks: 37%; 24 weeks: 66%; 36 weeks: 72%; 48 weeks: 89%.
	The time it took to achieve undetectable HBV was significantly affected by baseline viral load.
	At 48 weeks, 17 patients had only a partial virological response, with a median 2.5 log IU/mL residual viremia.
	Among nucleoside/nucleotide-experienced or resistant patients, viral load remained undetectable in those who switched from adefovir (Hepsera) to tenofovir.
	HBV DNA became undetectable in 74% of patients with ongoing HBV replication due to resistance at baseline (median HBV DNA 4.1 log IU/mL), independent of treatment strategy.
	In a pooled safety assessment, 3% of patients had a serum creatinine increases greater than 0.3 mg/dL, and < 1% had increases greater than 0.5 mg/dL, compared with baseline levels.
	8% of patients saw their blood phosphorus level fall below 2.3 mg/dL, another sign of kidney impairment.
	37% had their urinary phosphate absorption (as assessed by estimated TmPI/GFR) decrease below 0.7 mmol/L.
	Most of these patients, however, had long-term previous exposure to adefovir, which can also cause kidney dysfunction.
	6% of patients reduced their tenofovir dose due to worsened creatinine clearance.
	Most patients in this group were older than 60 years, had previous exposure to adefovir, were taking other potentially nephrotoxic (kidnet toxic) medications, and/or had other conditions associated with poor kidney function.

"Tenofovir suppressed HBV replication in most [nucleoside/nucleotide]-naive and [nucleoside/nucleotide]-experienced or resistant patients in field practice," the investigators concluded. "Few patients showed an impaired renal and tubular function of multifactorial origin."

Investigator affiliations: 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy; Gastroenterology Division, University of Ankara Medical School, Ankara, Turkey; Hospital General Universitario Valle Hberon and Ciberehd, Barcelona, Spain; 2nd Dept. of Internal Medicine, Hippokration Hospital, Athens, Athens, Greece; SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda, Milano, Italy; Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni, Bergamo, Italy; UO Epatologia, Ospedale di Treviglio, Treviglio, Italy; S.C. Medicina Generale, Ospedale A. Manzoni, Lecco, Italy; Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo, Italy; Unita Operativa di Medicina, Servizio di Epatologia, Ospedale Sant' Anna, Como, Italy; Unita Operativa di Gastroenterologia, Fondazione Poliambulanza, Ospedale S.Orsola, Brescia, Italy; Clinic of Infectious Diseases, Universita di Foggia, Foggia, Italy; I and II Div. Infectious Diseases, Ospedale Luigi Sacco, Milano, Italy; Liver Center, Clinica Medica, Azienda Ospedaliera S. Gerardo, Università Milano Bicocca, Monza, Italy; UO Gastroenterologia, Ospedale Valduce, Como, Italy; Infectious Diseases, Ospedali Riuniti di Bergamo, Begamo, Italy.

11/23/10

Reference
P Lampertico, M Vigano, C Yurdaydin, and others. Effectiveness and safety of Tenofovir disoproxil fumarate in field practice: a multicenter European cohort study of 737 patients with chronic hepatitis B. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 369.