Unknowns in Treatments for Chronic HBV

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Hepatitis Researcher Identifies Unknowns in Treatments for Chronic HBV



By Harvey S. Bartnof, MD



Jay A. Hoofnagle, MD, discussed state-of-the-art therapy for treating chronic HBV (hepatitis B virus) infection during his presentation at the recent 3rd International Conference on Therapies for Viral Hepatitis. Dr. Hoofnagle is the Director of the Division of Digestive Diseases and Nutrition at the NIDDK (National Institute of Diabetes and Digestion and Kidney Diseases) at the NIH (National Institutes of Health). Chronic hepatitis B affects approximately 350 million people in the world, equaling approximately 5% of the world's population. It is a major cause of cirrhosis (liver scarring) and primary liver cancer (hepatocellular carcinoma). Each of these complications is life-threatening.



Dr. Hoofnagle briefly reviewed the current therapies for hepatitis B. The only FDA-approved therapies are Intron A (alfa * interferon) or Epivir-HBV (lamivudine, 3TC). (Note that the other brand or trade names of alfa interferon are not FDA-approved for chronic hepatitis B.) Dosing with Intron A is 30-35 million units weekly for 16 weeks (adults) or up to 30 million units weekly for 16 -24 weeks (pediatrics). This leads to "seroconversion" that is sustained after therapy is stopped for only 25-35% of patients. Seroconversion is defined as a loss of hepatitis B "e" antigen, development of "e" antibodies, and achieving an undetectable HBV DNA viral load.



Epivir-HBV at a dose of 100 mg daily for one year leads to seroconversion in 17-33%. In a limited number of patients treated and followed for a longer period, the seroconversion rate continues to increase. After one year of Epivir-HBV, other improvements occur in a high proportion of patients. These include decreases in HBV DNA viral load, a decrease in the liver enzyme ALT (alanine aminotransferase) and an improved liver histology (appearance of a biopsy sample under the microscope). Resistance to Epivir-HBV after one year develops in 14-32%, but this does not necessarily reverse all of the drug's benefits. Treating with Epivir-HBV for longer than one year also leads to increasing rates of resistance to Epivir-HBV. After two years, the resistance rate is approximately 40%.

medline

it is a good article, it briefly review the useage of alfa-interferon&lamivudine.



but I don't understand the titile

"Unknowns in Treatments for Chronic HBV "

what 's the unknowns?

liver411

I am so sorry. I got the 2nd part of the mail much later and had problem to put into color back groud frames and talbes(they are not pictures). Instead, I put them in as words. I gusess this is the "unknowns" of unknown. - Unknown=Pitfalls. Hepatitis Researcher Identifies Unknowns in Treatments for Chronic HBV Pitfalls of Intron A Dr. Hoofnagle reviewed some of the pitfalls of therapy with Intron A. First is that the response rate is only approximately one-third. Second, a high dose is required "for at least four months." Third, due to side effects ("flu"-like symptoms), many patients do not tolerate this drug well. Fourth, many patients do not like the daily or 3-times weekly injections. Fifth, occasionally, the side effects are serious. And lastly, the drug is expensive. An advantage of Intron A over Epivir-HBV is the shorter, finite treatment period that is FDA-approved Pitfalls of Epivir-HBV In contrast, Epivir-HBV has some advantages and different or similar pitfalls. First, it is easier to administer-many patients prefer taking an oral pill instead of injections. Yet, the response rate is similar to that of Intron A: only one-third. Another potential disadvantage is the development of resistance, although the complete significance of this is not yet completely known. Lastly, another disadvantage is the long duration of therapy at one year. Yet, it has an "excellent record of safety and tolerability," says Dr. Hoofnagle. The side effect profile is nil, and it is much better tolerated than Intron A. Yet there are several unanswered questions that Dr. Hoofnagle subsequently addressed. They include the following: Are there any benefits to using the two drugs sequentially? If so, should Intron A or Epivir-HBV be used first? Is there any benefit to combining the two therapies? (The answer to this last question may be 'yes,' see next report below.) Is there any role for longer, continuous treatment with either therapy than what is currently FDA-approved? Are those patients who respond to Intron A the same ones that would respond to Epivir-HBV? And vice-versa? To help determine which therapy should be used, are there any clinical or virological characteristics of patients that would help? Are normal laboratory markers of viral hepatitis that are achieved during therapy helpful in deciding the best time for stopping therapy? Are persistently abnormal markers after a given period of time of therapy helpful in deciding that additional therapy would be of no benefit? (Potential markers include: liver enzymes [ALT, AST], HBV DNA viral load, "e" antigen, "e" antibodies, surface antigen, and liver biopsy changes.) What should the treatment be for patients with complicated, severe or atypical types of chronic hepatitis B? Which improved laboratory markers correlate best with improved histologic (under the microscope) appearances and/or decreased rates of liver disease progression including cirrhosis (scarring), liver failure and primary liver cancer? To address some of these issues, Dr. Hoofnagle announced a Workshop that will be held next year at the NIH. The title is, "Management of Hepatitis B: 2ks." It will be held in September on the NIH campus, Natcher Auditorium. Topics that will be addressed include diagnosis, monitoring, therapy and prevention of hepatitis B. During her presentation entitled "Treatment of Chronic Hepatitis B," Anna S. F. Lok, MD, reviewed that two groups of patients with more advanced hepatitis C disease should be treated with Epivir-HBV and not with Intron A. Dr. Lok is the Director of Clinical Hepatology at the University of Michigan in Ann Arbor. She also identified five groups of patients with chronic hepatitis C, their respective laboratory markers, and their respective treatment options. They are as shown: Treatment Options for Various Groups of Patients with Chronic Hepatitis B (table) Group Number Hepatitis "e" Hepatitis B Liver Disease Treatment Antigen DNA Viral &/or ALT Level Option Status Load # 1 Positive Detectable Normal Observe *** 2 Positive Detectable Abnormal Intron A (Increased) or Epivir-HBV 3 Negative Detectable Abnormal Intron A (Increased) or Epivir-HBV 4 Positive Detectable Decompensated Epivir-HBV or Negative Cirrhosis ** 5 Positive Detectable Recurrent Epivir-HBV or Negative Disease after Liver Transplant Adapted from Anna S. F. Lok, MDbb Key #ALT is alanine aminotransferase (liver enzyme). *All generic versions use the spelling 'alfa' and not 'alfa.' **Decompensated cirrhosis means the liver is unable to function normally, but has not yet failed. Treating with Intron A at that time could trigger liver failure. ***Observe means that no drug therapy is indicated at that time, and that the patient needs re-evaluation periodically to determine whether therapy would help at a later time. As indicated in the table above, Intron A should not be used in those patients in Group 4 (decompensated cirrhosis **, see Key from table above) or Group 5 (recurrent hepatitis B disease after liver transplantation). However, Epivir-HBV is indicated for both groups. Group 1 refers to those patients with a normal ALT (#--see Key from table) enzyme level, but who do have "e" antigen and detectable HBV DNA. These patients do not respond well to either treatment, and should be observed (***, see Key from table). Either drug treatment is indicated for those patients in Group 2, with "e" antigen, detectable HBV DNA, and an increased ALT. Either drug treatment also is indicated among those patients without "e" antigen, but who do have detectable HBV DNA, an increased ALT, yet without liver decompensation (Group 3). Note that Dr. Hoofnagle presented the results of the first study that revealed an improved response when the two therapies were combined in Group 3 patients.

medline

Thanks , a very helpful article.

This article asks many questions .

Research to answer these questions will help the treatment of chronic HBV