Thiamine Treatment of Chronic Hepa B Infection II

liver411

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From: "The Martin's"

To: "HBList" <[email protected]>

Subject: [HB] Thiamine Treatment of Chronic Hepatitis B Infection-page 2

Date: Fri, 27 Apr 2001 07:06:55 -0400



MATERIALS AND METHODS:

We were stimulated to look into this relationship based on a patient's

observation that his aminotransferase levels fell and rose depending on whether or not he took thiamine.  In that case (case report 1) we collected historic aminotransferase levels, hepatitis markers, and thiamine use based on Veterans Administration hospital pharmacy refill information and chart review, and we noticed a relationship between thiamine use and reduced aminotransferase levels.  In case two, after obtaining approval from the chief of staff, the chief of gastroenterology, and the facility ethics committee, and after obtaining informed consent from the patient, we prospectively collected transaminase and hepatitis marker data in an open trial of thiamine in a patient with hepatitis B.  Thiamine was discontinued

with aminotransferase levels fell to normal and was restarted when levels rose.  With this pilot data, we obtained institutional review board approval to recruit subjects for a placebo-controlled trial examining thiamine treatment of patients with chronic hepatitis B or C.  The third case report represents the single recruit for the hepatitis B arm of the study, and data were collected prospectively.  All three patients presented had either failed or not tolerated interferon treatment.



Case 1

A 56 year old man with stable bipolar affective disorder and alcohol

dependence in remission for 8 years was diagnosed was diagnosed with chronic active hepatitis B, presumed to have been contracted during his military service in southeast Asia in 1973.  His bipolar illness had been well controlled on Lithium carbonate for 15 yr.  Chronic active hepatitis B was diagnosed when aminotransferase levels rose and failed to normalize after steroid pulse treatment for back pain , and was confirmed by liver biopsy, which revealed bridging fibrosis and early cirrhosis.  Thiamine

administration (100 mg daily) commenced on day 112 in Figure 1.  In days 250 through 259, the patient received i.m. a-interferon , 5 million U daily.



Interferon therapy was discontinued after 9 days when the patient became delirious.  Aminotransferase levels rose during brief interferon treatment, then gradually decreased to within normal limits over the following year.



Thiamine was discontinued on day 610.  Over the subsequent 50 months, two additional crossovers were conducted.  During each period of thiamine administration, aminotransferase levels fell.



Hepatitis studies were incomplete before thiamine administration.  HBsAg was positive at the time of diagnosis, corresponding to day 0 in figure 1.  On day 676, total bilirubin peaked at 1.4 mg/dL .  On day 799, hepatitis B e antibody (HBeAB) was positive, and HBV DNA, hepatitis B e antigen (HBeAg), hepatitis C antibody, and delta antigen were negative.  Hepatitis studies were checked at 6-month intervals thereafter: HBeAB remained positive, and HBsAg was eventually lost 3 yr later.



Except for the changes in the administration of thiamine, no changes were made in the patient's medication regimen after his brief treatment with interferon.  The patient reported no alterations in health, social, recreation or occupational habits over this time period.  He denied use of alcohol or other non prescribed substances during the study.



Case 2

A 52-year old man, had a medical history notable for hospitalization for

Guillain-Barre syndrome, from which he recovered with residual weakness and lethargy.  Although his aminotransferase levels were within normal limits at the time of hospitalization, he was found to be HBsAg and HBeAg positive, with exposure presumed to have been during his military service in southeast Asia 30-yr prior.



Three years before thiamine administration, ALAT (ALT) and aspartate

aminotransferase (AST) were noted to be elevated to 1.5 times normal upper limits.  Liver biopsy at that time confirmed florid chronic active hepatitis.  Alpha interferon (5 million U daily) was administered

subcutaneously for 4 months, ending approximately 2.5 years before thiamine administration.  Interferon was discontinued early because of severe depression, weakness, and lethargy presumed related to interferon.  ALT and AST decreased to just within normal limits shortly after interferon discontinuance.  Aminotransferase levels had risen to preinterferon levels at time 0 on Figure 2 and remained elevated over the subsequent 2-yr.  The patient was started on thiamine hydrochloride, 100 mg p.o. daily, on day 705.  Aminotransferase levels decreased to within normal limits, and thiamine was discontinued on day 756.  Aminotransferase levels again rose, and thiamine was restarted on day 886.



Nearly 2-year after interferon and six months before thiamine

administration, HBsAg transiently converted to HBeAB and HBV DNA became undetectable, corresponding to the aminotransferase nadir on day 474 on the chart; HBsAg remained positive.  By the time thiamine administration began on day 705, HBV DNA and HBeAg were again positive.  Liver biopsy on day 970 showed a decrease in inflammation compared with biopsy taken before interferon or thiamine treatment.  HBV DNA became undetectable on day 1930,

although HBeAg remained positive.



Except for the changes in the administration of thiamine, no changes were made in the patient's medication regimen after his brief treatment with interferon.  The patient was exposed to solvents daily from days 1209 to 1239 on the chart, corresponding to the mild increase in aminotransferase levels and the marked elevation of GGT.  He denied use of alcohol or other nonprescribed substances during the study.



Case 3

A 49-yr old man with prior history of alcohol dependence and posttraumatic stress disorder (PTSD) was diagnosed with chronic active hepatitis B when aminotransferases failed to normalize despite abstinence from alcohol, approximately 5-yr before thiamine treatment.  HBsAg and HBeAg were positive and HBV DNA was present at the time of diagnosis.  Exposure to hepatitis B was presumed to have been during his military tour in southeast Asia 25-yr

prior.  The patient declined liver biopsy and interferon treatment.  On day 6, he was hospitalized for detoxification after a 1-month alcohol relapse that corresponded to a peak in aminotransferase levels and total bilirubin (9.6 mg/dL).  By day 38, aminotransferase levels had stabilized.  Thiamine hydrochloride (100 mg p.o. per day) was initiated on day 123 in Figure 3.



Over the subsequent 6 months, aminotransferase levels normalized, HBeAg converted to HBeAb, and HBV DNA became undetectable.  Thiamine was restarted on day 445, aminotransferase levels fell to normal limits 1 month thereafter.



In addition to the changes of the administration of thiamine, the patient was placed on a variety of medications for hypertension (metoprolol, lisinopril, captopril, and clonidine) chronic pain (MS Contin),

gastroesophageal reflux disease prophylaxis (lansoprazole), and PTSD

(lorazepam), in association with a voluntary hospitalization for PTSD,

beginning on day 505.  Some of these medications were discontinued within a month.  The timing of the initiation of these medications corresponds to the mild elevation in aminotransferase levels in Figure 3.  The patient reported no alterations in social, recreation, or occupational habits over the study period.  He denied use of alcohol or other unprescribed substances during the study.







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