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HIV and Coverage of the
45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010)

April 14 - 18, 2010, Vienna, Austria
Telbivudine (Tyzeka) Produces Better Outcomes than Lamivudine in Hepatitis B Patients with Decompensated Cirrhosis

SUMMARY: Telbivudine (Tyzeka) led to better outcomes than lamivudine (Epivir-HBV) for chronic hepatitis B patients with decompensated cirrhosis, increasing the likelihood of HBV viral load suppression and ALT normalization, according to a study presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) this month in Vienna. In this analysis, telbivudine had a safety profile similar to lamivudine and was associated with improved liver and kidney function. Another study, however, found that telbivudine in combination with pegylated interferon can cause peripheral neuropathy.

By Liz Highleyman

Over years or decades, chronic hepatitis B can progress to advanced liver disease, including hepatocellular carcinoma, cirrhosis, and liver failure. Decompensated cirrhosis -- meaning the liver can no longer carry out its vital functions -- is associated with high morbidity and mortality, yet treatment options are limited.

Antiviral agents can lower HBV levels in people with advanced cirrhosis, but they may cause side effects that patients with severe illness are unable to tolerate. Lamivudine is generally well-tolerated, but it is prone to resistance that can compromise long-term effectiveness.

Most people with decompensated cirrhosis patients have some degree of kidney impairment, indicating that adefovir (Hepsera) and tenofovir (Viread), which can worsen kidney dysfunction in susceptible individuals, should be used with caution. (Another study presented at the EASL meeting, however, showed that tenofovir/emtricitabine appears safe in patients with mild-to-moderate kidney impairment after liver transplantation.)

Edward Gane from Middlemore Hospital in Auckland, New Zealand, and colleagues conducted a study comparing treatment outcomes with telbivudine versus lamivudine in decompensated chronic hepatitis B patients.

This double blind trial included 232 patients with decompensated liver disease, defined as a Child-Turcotte-Pugh score above 7 and cirrhosis or portal hypertension. About three-quarters were men, 65% were Asian, the median age was about 50 years, and about 57% were hepatitis B "e" antigen (HBeAg) negative.

Study participants were randomly assigned to receive 600 mg telbivudine or 100 mg lamivudine for 104 weeks.


In a 2 year intent-to-treat analysis, 49% of patients receiving telbivudine achieved undetectable HBV DNA (< 300 copies/mL), compared with 40% in the lamivudine arm (P = 0.15, not a significant difference).
73% of participants in the telbivudine arm and 62% in the lamivudine arm experienced ALT normalization (P = 0.25, also not significant).
Looking at a composite endpoint of undetectable HBV DNA and ALT normalization, however, telbivudine performed significantly better than lamivudine (34% vs 24%, respectively; P = 0.004)
28% of telbivudine recipients experienced viral breakthrough while on therapy, compared with 37% of lamivudine recipients (P = 0.16).
At the end of treatment, about 75% of patients in both arms had stabilized or improved liver disease, as indicated by changes from baseline in Child-Turcotte-Pugh scores.
Kidney function (indicated by glomerular filtration rate) modestly improved in the telbivudine arm, while worsening in the lamivudine arm.
Early (week 24) survival rates were similar in the 2 study arms, 96% with telbivudine and 92% with lamivudine.
Long-term (week 104) survival rates were 87% and 79%, respectively, with a trend toward statistical significance.
Serious adverse events were common, consistent with advanced liver disease, and occurred with similar frequency in both arms (51% of telbivudine recipients vs 59% of lamivudine recipients).
No cases of rhabdomyolysis (muscle damage due to drug toxicity) or lactic acidosis (associated with mitochondrial toxicity) were reported.

Based on these findings, the investigators concluded, "In a large number of patients with long term follow-up telbivudine was well tolerated with stabilization of liver function and comparable tolerability to lamivudine."

Peripheral Neuropathy

Another study sounded a note of caution, however. Patrick Marcellin and colleagues reported that telbivudine plus pegylated interferon led to a higher rate of undetectable HBV viral load and greater reductions in HBeAg and hepatitis B surface antigen (HBsAg) than either drug alone. However, patients receiving combination therapy were more than twice as likely to experience adverse events.

Of particular concern, peripheral neuropathy (nerve damage) developed sooner and was more severe in the combination arm, leading to premature discontinuation of the study. Telbivudine is a thymidine nucleoside analog, a class of drugs associated with peripheral neuropathy, facial fat loss, and other manifestations associated with mitochondrial toxicity in people treated for HIV.

The investigators recommended that "[d]espite increased efficacy, concomitant use of [pegylated interferon + telbivudine] should be avoided at present."

Investigator affiliations:

Gane study: Middlemore Hospital, Auckland, New Zealand; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China; Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Phramongkutklao Hospital, Bangkok, Thailand; Holy Family Hospital, Nazareth & Hadassah Medical Center, Jerusalem, Israel; Siriraj Hospital, Bangkok; Chiang Mai University, Faculty of Medicine, Chiang Mai, Thailand; Sieff Government Hospital, Safed, Israel; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; Novartis Pharma Corporation, East Hanover, NJ.

Marcellin study: Service d'Hépatologie, INSERM, Hôpital Beaujon, Clichy, France; Novartis Pharma AG, Basel, Switzerland; Hannover Medical School, Hannover, Germany; Kaohsiung Medical University, Kaohsiung, Taiwan ROC; Clinical Trial Center, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China; China Medical University Hospital, Taichung, Taiwan ROC; Middlemore Hospital, Auckland, New Zealand; Hospital de Enfermedades Infecciosas, Buenos Aires, Argentina.


EJ Gane, HL Chan, G Choudhuri, and others. Treatment of decompensated HBV-cirrhosis: results from 2-years randomized trial with telbivudine or lamivudine. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).

P Marcellin, C Avila, K Wursthorn, and others. Telbivudine (LdT) plus peg-interferon (pegIFN) in HBeAg-positive chronic hepatitis B -- very potent antiviral efficacy but risk of peripheral neuropathy (PN). 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).