Managing Liver Toxicities

[Guest guest]

Here's an interesting paper. SNMC is an *injectable* extract of

glycyrrhizin (licorice extract). Whether oral forms work as well isn't

known.

Also, re CoQ10, check out also

www.newyorkbuyersclub.org (have 30 mg size inexpensively) and

www.consumerlab.com

M.

**

http://www.nih.go.jp/JJID/LEC-36.html

Jpn. J. Infect. Dis., 52, 1999

Laboratory and Epidemiology Communications

Mitigation of Hepato-Cellular Injury Caused by HAART with

Glycyrrhizin Compound in Patients Co-Infected with HIV and HCV

Yoshihiko Yamamoto1,2, Akira Yasuoka1,

Natsuo Tachikawa1, Katsuji Teruya1, Ikumi

Genka1, Masazumi Yamaguchi1, Chie

Yasuoka1, Yoshimi Kikuchi1, Makoto Aoki1

and Shinichi Oka1

1AIDS Clinical Center, International Medical Center of

Japan, Toyama 1-21-1, Shinjuku, Tokyo 162-8655 and 2The

Organization for Pharmaceutical Safety and Research of Japan,

Kasumigaseki 3-3-2, Chiyoda, Tokyo 100-0013

Communicated by Hiroshi Yoshikura

(Accepted January 5, 1999)

Hepato-cellular injury occurring several weeks after initiation of highly

active anti-retroviral therapy (HAART) against HIV infection is not

infrequent. In most cases, increase of serum alanine aminotransferase

(ALT) is transient and it decreases spontaneously without any treatment.

However, some patients dually infected with HIV and hepatitis virus are

obliged to discontinue HAART because of moderate or severe

hepato-cellular injuries (1,2). In our hospital, 48 out of 270 patients

who had been receiving protease inhibitors since 1997 developed high

serum ALT level (increase by more than three-fold of basal values and/or

more than 200 IU/L [normal range 0-30]).

Incidence of the hepatitis C virus (HCV) infection is relatively high in

Japan; almost all Japanese HIV-infected hemophiliacs have tested positive

for antibodies to HCV. Currently, a glycyrrhizin compound

Stronger-neo-Minophagen C (SNMC) is widely used to treat hepato-cellular

injury in all patients with HCV. Glycyrrhizin is reported to have a

protective effect on hepatocyte (3). SNMC consists of 0.2% glycyrrhizin,

0.1% cysteine, and 2.0% glycine in physiologic saline, and has been

approved by the Ministry of Health and Welfare of Japan in the treatment

for chronic hepatitis. Here we report a successful mitigation of

HAART-induced hepato-cellular injury with SNMC without reduction or

discontinuation of any anti-HIV drugs.

Four hemophiliacs (cases 1-4), dually infected with HIV and HCV, had

moderate hepato-cellular injury after initiation of HAART (stavudine,

lamivudine, and protease inhibitors). Their ALT levels were mildly

elevated before HAART, indicating that they had chronic active hepatitis.

They had nausea and general malaise, and showed further increase of ALT;

more than 280 to 480 IU/L within 5 weeks after initiation of HAART (case

2, 14 weeks later). Cases 1 and 3 had to discontinue HAART as a result of

hepato-celluar injury. These patients were then hospitalized and

administered with SNMC intravenously, and HAART was reinitiated after we

had obtained informed consent.

Daily administration of SNMC was started with initial doses of 40 to 80

ml and gradually tapered with careful monitoring of ALT. SNMC was

administered for 16 to 46 days. Clinical complaints disappeared from all

of these patients within 10 days, and serum ATL values immediately

declined, reaching less than 100 IU/L within 4 weeks (Fig.). As a

consequence, all of these patients were able to continue HAART without

reducing any anti-HIV drugs. Although ALT of all patients did not stay

within the normal limit, further elevation of ALT was not observed up to

4 months after completion of SNMC. No side effects, such as the

pseudo-aldosteronism often induced by the glycyrrhizin (3) in SNMC, were

observed. Evaluation of HCV viral load showed no significant changes such

as those observed in other HCV (+) / HIV (-) patients. HIV-1 viral load

was suppressed to less than 200 copies/ml within 2 months in cases 2, 3,

and 4, and was decreased to 4400-2200 copies/ml within 4 weeks in case 1,

indicating that HIV-1 viral load was adequately suppressed in all

clinical courses. In addition, another hemophiliac patient who showed

persistent elevation in serum ALT for 5 months after discontinuation of

previous HAART (AZT, ddC, and SQV), was administered with SNMC. His ALT

had declined to 335-61 IU/L within 19 days, and he was able at that time

to reinitiate another HAART regimen (d4T, 3TC, and RTV). His ALT level

remained lower than 96 IU/L for the following 6 months.

The precise action mechanism of SNMC is still unclear. However, SNMC is

very popular, largely because its efficacy has been confirmed by many

Japanese physicians through the traditional treatment of liver

dysfunction in Japan. Hepato-cellular injury after HAART can be caused by

three possible mechanisms; side effects by HAART itself, exacerbation of

HCV hepatitis, and transient local immune response to HCV in the course

of immune reconstitution (4). The cause of the hepato-cellular injury in

these four cases was unclear. However, the third mechanism is most likely

because there were no significant increases of HCV viral load nor any

signs of exacerbation of HCV hepatitis in any patients. SNMC is

cost-effective and has a low toxicity. This limited pilot study indicated

that a larger clinical trial is warranted for cases suffering from

hepato-cellular injury as a result of HAART.

This work was supported by grants from the Ministry of Health and Welfare

of Japan, and the Organization of Pharmaceutical Safety and Research

(OPSR) of Japan.

REFERENCES

Matsuda, J., Gohchi, K. and Yamanaka, M. (1997): Severe hepatitis in

patients with AIDS and haemophilia B treated with indinavir. Lancet, 350,

364. Brau, N., Leaf, H.L., Wieczorek, R.L.and Margolis, D.M. (1997):

Severe hepatitis in three AIDS patients treated with indinavir. Lancet,

349, 924-925. van Rossum, T.G., Vulto, A.G., de Man, R.A., Brouwer, J.T. and

Schalm, S.W. (1998): Review article: glycyrrhizin as a potential

treatment for chronic hepatitis C. Aliment. Pharmacol. Ther., 12,

199-205. , M., Flexman, J. and French, M.A. (1998): Hepatitis C

virus-associated hepatitis following treatment of HIV-infected patients

with protease inhibitors: an immune restoration disease? AIDS, 12,

2289-2293.

*Corresponding author: Fax: +81-3-5273-5193, e-mail:

oka@...