A team of doctors in Japan has found the medication lamivudine, marketed as Epivir-HBV, may be effective for people with advanced liver cirrhosis caused by hepatitis B infection.1
"The prognosis for patients with decompensated hepatitis B virus (HBV)-related liver cirrhosis, especially for those with hepatocellular carcinoma, is poor," wrote Morikazu Onji, MD, PhD, in the department of Internal Medicine at Ehime University School of Medicine in Ehime, Japan, and his cohorts.
The researchers began a small study to find out if prescribing lamivudine for these patients would improve their dismal prognosis.
Expanded Indication?
Lamivudine, manufactured by GlaxoSmithKline, is an oral medication for people with chronic hepatitis B. According to its prescribing information, the medication has shown it can significantly improve Complete Virologic Response, defined as no further evidence of the viral antigen (a molecule on the virus that sparks an immune response) nor HBV DNA, the virus' genetic material used as an indicator of its presence in the body. But it's not known whether lamivudine is effective for those with hepatocellular carcinoma or advanced cirrhosis. Whether a response to the therapy might mean the drug is effective against these two conditions isn't yet known. The recommended dose is 100 mg per day for adults.2
While there are other drugs for hepatitis B, lamivudine was tested in this study because other drugs haven't been as effective against HBV-related cirrhosis, explained Fazle Akbar, MD, PhD, one of the study's investigators, also in the department of Internal Medicine at Ehime University.
Onji and his team examined the medical records of 55 people with advanced HBV-related liver cirrhosis and with and without liver cancer, for the trial. Each of the patients had been admitted to hospitals in the area between 1997 and 2004. Those with advanced disease due to an intense form of chronic hepatitis B, as well as patients with liver cancer that had spread to other areas or those with a portal vein tumor thrombus were not included since these represented cases outside of the pathology being studied.
Nineteen of the patients, including five who had liver cancer at the start of therapy, were treated with 100 mg doses of lamivudine per day. By contrast, 36 patients had not been treated with the medication.
Those in the medication group had more advanced cirrhosis than those in the group not given the drug, based on median Child-Pugh classification, a scoring system that measures the severity of the liver condition.3
'Significant' Improvements Found
The study lasted for a total of 6 months. At the end of this treatment period, Onji and his colleagues learned that prothrombin time, albumin, ascites, the extent of cirrhosis, and viral load "were each significantly improved" in the group of patients that had been given lamivudine therapy. (Prothrombin time is the measurement of the length of time it takes for blood to clot. In people with liver disease, blood clotting can become impaired, thus prothrombin time takes longer. Albumin is a substance made the liver. Lower levels can indicate that a patient has edema or ascites—a form of fluid build-up in the abdomen associated with a dysfunctional liver.)4
While cirrhosis was more advanced for those in the treatment group before therapy began, it was "improved after therapy beyond those not given lamivudine," explained Akbar.
Drug Resistance Noted
Five patients in the treatment group had experienced a form of lamivudine resistance due to a mutation, or abnormality, in the virus, "however, liver function did not deteriorate," wrote the study team. This form of viral resistance, which may occur after long-term lamivudine use, may lead to a hepatitis B flare-up in nearly two-thirds of patients taking the therapy.5,6
Survival odds for those taking lamivudine also significantly improved, Onji's team noted. Liver cancer was diagnosed in three patients in the treatment group and four in the non-treatment group during the study. In the therapy group, all patients with diagnosed liver cancer were treated repeatedly or until cured, whereas an overwhelming majority of those in the non-lamivudine group could not be treated for their cancer, the researchers wrote.
"Our results suggest that lamivudine is a useful and important therapy for patients with decompensated HBV-related liver cirrhosis with and without hepatocellular carcinoma, as well as those who are restricted from having liver transplantation," the research authors concluded.
Echoing Other Research Results
A similarly sized study from Japan published last year also touted the benefits of lamivudine for those with HBV-related cirrhosis, at least in those who had no drug resistance.7
Fifty-four Japanese patients with cirrhosis due to HBV infection were recruited and given daily doses of the medication for an average of two years. However, no comparison group was used in this study. After one year of treatment, nearly 80 percent of the patients had no detectable levels of HBV DNA. But after two years of therapy, about 61 percent of the patients responded. Approximately one-third of the patients in the study had improvements in their cirrhosis before lamivudine resistance was detected. No change in cirrhosis progression was seen in the other two-thirds.
Eventually, about 35 percent developed resistance to the drug, especially in those diagnosed with cirrhosis. Once this occurred, one-quarter of those with resistance saw their cirrhosis progress further.
"Lamivudine therapy improved the clinical course in some cirrhotic patients," the study investigators wrote. "However, in patients with [more advanced] cirrhosis, the emergence of [medication resistance due to viral mutations] sometimes led to deterioration of liver function."
1. Hiraoka A, Michitaka K, Kumagi T et al. Efficacy of lamivudine therapy for decompensated liver cirrhosis due to hepatitis B virus with or without hepatocellular carcinoma. Oncol Rep 2005 Jun;13(6):1159-63.
2. Hepatitis Neighborhood. HBV Medications: Intron-A, Epivir HBV, Hepsera & Baraclude. Available at: http://www.hepatitisneighborhood.com/content/treatment_options/
medications_for_hepatitis_287.aspx. Accessed June 29, 2005.
3. Burroughs A, Samonakis D. Is transarterial chemoembolization an option for all patients with unresectable hepatocellular carcinoma? Nature Clinical Practice Gastroenterology & Hepatology 2004;1:78-9. doi: 10.1038/ncpgasthep0038.
4. Hepatitis Neighborhood. Common Liver Lab Tests. available at: http://www.hepatitisneighborhood.com/content/understanding_hepatitis/
diagnosing_hepatitisc_134.aspx. Accessed June 29, 2005.
5. Sokal E. Lamivudine for the treatment of chronic hepatitis B. Expert Opin Pharmacother 2002 Mar;3(3):329-39.
6. Rizzetto M. Efficacy of lamivudine in HBeAg-negative chronic hepatitis B. J Med Virol 2002 Apr;66(4):435-51.
7. Ooga H, Suzuki F, Tsubota A et al. Efficacy of lamivudine treatment in Japanese patients with hepatitis B virus-related cirrhosis. J Gastroenterol 2004 Nov;39(11):1078-84.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
