Thiamine Treatment of Chronic Hep B Infection I

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From: "The Martin's"

To: "HBList" <[email protected]>

Subject: [HB] Thiamine Treatment of Chronic Hepatitis B Infection-page 1

Date: Fri, 27 Apr 2001 07:06:12 -0400



          Vol. 96 Number 3 2001

           ISSN 0002 9270/01/$20.00

           PII S0002 9270 (00)02428-X



Amy Elizabeth Wallace, M.D., William Brinson Weeks, M.D.,M.B.A.

Departments of Psychiatry and Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire; Veterans Administration Medical Center, White River Junction, Vermont; and the Veterans Administration Medical Center, Manchester, New Hampshire



OBJECTIVE: Chronic Hepatitis B is an international health concern that

causes cirrhosis, hepatocellular carcinoma, liver failure, and death.  Current treatment options are expensive and associated with side effects; however, indirect evidence suggests a  relationship between relative thiamine deficiency and chronic hepatitis B infection.



METHODS: The authors present three case studies wherein multiple crossovers of daily thiamine administration were used to evaluate a hypothesized association between thiamine treatment and aminotransferase levels.



RESULTS:  In each case study, thiamine administration was associated with reduction in aminotransferase levels and the fall of HBV DNA to undetectable levels.  Analysis by t test demonstrated a significant reduction in aminotransferase levels in all three cases.



CONCLUSIONS:  The relationship between thiamine administration and chronic hepatitis B warrants study.  If proven effective reducing liver damage or inducing remission of the hepatitis B virus in larger trials, thiamine will offer obvious advantages over the current treatments for viral hepatitis B infection.(Am J Gastroenterol 2001;96:864-868. C. 2001 by Am Coll. of Gastroenterology)



INTRODUCTION:

Chronic hepatitis B is a serious health concern that may lead to cirrhosis, hepatocellular carcinoma, liver failure and death (1).  It is a prevalent disease that is anticipated to affect 400 million people worldwide by the year 2000(2).  The chronic active form is diagnosed when the hepatitis B surface antigen (HBsAg) is present and aminotransferase levels are elevated for at least six months (3).  Impaired cell-mediated immune response to the hepatitis B virus is the theorized mechanism for persistent infection (4).



Several antiviral treatments have been proposed for the treatment of chronic viral hepatitis.  Alpha interferon, the most promising treatment to date, is effective in inducing long-term remission in only 25-40% of treated patients (5).  Yearlong treatment with lamivudine reduced aminotransferase levels in chronic hepatitis B and was associated with a HBeAg seroconversion rate of 16% (6). Despite the promise of these agents, many who might benefit are unable to tolerate physical and psychological side effects (7).



There are three lines of circumstantial evidence that suggest a relationship between relative thiamine (vitamin B-1) deficiency and prevalence of chronic hepatitis B.



First, there is evidence that thiamine has direct antiviral properties.  In

an attempt to test the antihuman immunodeficiency virus (HIV) potential of various sulfur-containing compounds, one investigator found that only thiamine disulfide significantly reduced HIV production in vitro(8).









Second, thiamine may slow or reverse liver injury in chronic hepatitis B via reduction of iron overload.  Researchers have noted an association between elevated serum or hepatic iron level, increased rate of chronic hepatitis due to HBV, and poorer response to interferon therapy (9)(10).  Thiamine is required in the formation of dihydrolipoate, which in turn is responsible for the anaerobic removal of ferritin-bound iron at neutral pH (11). Relative thiamine deficiency would result in inadequate dihydrolipoate available for iron binding and removal. Excess and thereby toxic hepatic iron loads might predispose exposed individuals to progression to chronic hepatitis B infection.  Conversely, adequate or excess thiamine may promote

iron removal by dihydrolipoate, rendering hepatic cells less vulnerable to injury.



Third, there is epidemiological evidence that suggests a relationship

between thiamine-deficient populations and prevalence of hepatitis B

infection.  Thiamine is an essential coenzyme for many metabolic pathways, including the pyruvate dehydrogenase complex, a-ketoacid decaboxylase, and the synthesis of acetylcholine.  Thiamine deficiency (Beriberi) is rare in the United States except among chronic alcoholics, who have a higher prevalence of hepatitis B than the general US population( 12) . Thiamine deficiency is prevalent in East Asia, where enrichment of rice and wheat is not practiced (13), and hepatitis B infection is endemic to that population (14).



There is also indirect in-vivo evidence that thiamine may have ameliorative effects on HBV.  Using thiamine-enriched syrup as a placebo, Asian investigators have conducted several studies examining the effects of interferon on  HBV carrier children.  In one study of Chinese carrier children, there was an identical rate (17% over 18 months) of persistent loss of hepatitis B virus DNA (HBV DNA) between the interferon group and the thiamine-placebo group after a 12-week intervention (15).  In a separate study, a greater percentage of the thiamine-placebo experienced transient disappearance of the HBV DNA than did those in the group taking interferon alone or in the group taking interferon after prednisone withdrawal.  In addition, none of the thiamine/placebo group exhibited any signs of disease

progression evidenced by aminotransferase elevation while on the vitamin syrup for 6 months or at subsequent 1-month follow-up (16).  By comparison, a study examining the natural course of HBV in 420 Asian carrier children demonstrated a clearance rate of HBV DNA and HBsAg of only 0.6% annually (17).  These investigators conclusions that Chinese carrier children do not respond to interferon may have been confounded by the potential therapeutic effect of their placebo (thiamine).



Though circumstantial, this evidence suggests that the relationship between thiamine and HBV warrants further investigation.  The authors present three case reports that begin to examine this relationship.







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