Re: alkaline phosphatase. and fish oil

[Guest guest]

Dear Rita;

The only thing we've tried in an attempt to reduce our son's ALP

level is fish oils. It was clear that in repsonse to ursodiol, only

his ALT and AST came down dramatically, his ALP remained elevated.

We've looked into the possibility of trying a fibrate, based on

results obtained in Japan, mostly on PBC patients. An example of one

of the Japanese studies on fibrates is shown below. But we are

thinking that fish oils and fibrates may be acting on the same

target, and so have not pursued this.

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J. Gastroenterol. 40: 546-547 (2005)

Long-term fibrate treatment for PBC.

Nakamuta M, Enjoji M, Kotoh K, Shimohashi N, Tanabe Y

PMID: 15942724

To the Editor: In a previous issue of the Journal of Gastroenterology,

Kanda et al.1 reported a control trial, carried out for 6

months, to compare combination therapy of bezafibrate and

ursodeoxycholic acid (UDCA) versus UDCA alone. They demonstrated

that the combination therapy significantly reduced

serum levels of disease markers of primary biliary cirrhosis

(PBC), such as alkaline phosphatase (ALP) and gamma-glutamyl

transpeptidase (gGTP). In other studies, bezafibrate alone,2 or

in combination with UDCA,3–5 has been associated with similar

improvements in liver function test results. However, long-term

studies have not been performed yet.

We followed five female patients with PBC who received

fibrates (bezafibrate, 400 mg/day in three patients; fenofibrate,

150 mg/day in two) and UDCA (600 mg/day) for more than 25

months (range, 25 to 53 months; mean, 37.5 months). All cases

were diagnosed as PBC by histological findings, positivity for

antimitochondrial antibody (AMA), and high levels of IgM. All patients

had been treated with UDCA alone (600 mg/day) for more than 4 years

prior to the start of this treatment. Serum biochemical markers, such

as alanine aminotransferase (ALT), ALP, and cGTP were measured every

1–2 months.

Fig. 1. Time course of alkaline phosphatase (ALP) levels. Closed

squares, open squares, closed circles, closed triangles, and closed

diamonds represent the levels of ALP in each patient. UDCA,

ursodeoxycholic acid (sorry I can't include the figure!!!!)

Figure 1 shows the time course of ALP levels before and during

treatment. All patients showed a decrease in ALP levels soon after

the beginning of the treatment, and maintained these decreased

levels. The mean ALP levels during treatment (mean of the last

four sequential measurements) were significantly lower than those

before treatment (mean of four sequential measurements): 506.8

+/- 201.5 U/l (mean +/- SD) before treatment and 241.8 +/- 173.1 U/l

after treatment (P = 0.043; Wilcoxon signed-ranks test). The

mean ALT and gGTP levels were also decreased by the treatment

(ALT, before, 44.7 +/- 27.6 U/l vs after, 13.6 +/- 12.3 U/l; P =

0.079; gGTP, before, 221.7 +/- 84.5 U/l vs after, 98.5 +/- 41.1 U/l;

P = 0.079). Furthermore, treatment with fibrates reduced the level of

IgM significantly (before, 327.8 +/- 60.8 mg/dl, vs after, 171.8 +/-

28.4mg/dl; P = 0.043), and also halved the titer of AMA. There were no

side effects throughout the treatment. Interestingly, the patient

with the highest levels of ALP (closed squares in Fig. 1), who had

advanced PBC with mild jaundice, showed continuously decreasing

levels of ALP throughout the treatment, suggesting that fibrates also

seem to be effective for advanced PBC. Our findings suggest that

fibrates ameliorate PBC in the long-term, without side effects.

Controlled studies of a greater number of patients will be required

to confirm our findings.

References

1. Kanda T, Yokosuka O, Imazeki F, Saisho H. Bezafibrate treatment: a

new medical approach for PBC patients? J Gastroenterol 2003;38:573–8.

2. Kunihara T, Nimi A, Maeda A, Shigemoto M, Yamashita K.

Bezafibrate in the treatment of primary biliary cirrhosis: comparison

with ursodeoxycholic acid. Am J Gastroenterol 2000;95:2990–2.

3. Nakai S, Masaki T, Kurokohchi K, Deguchi A, Nishioka M. Combination

therapy of bezafibrate and ursodeoxycholic acid in primary biliary

cirrhosis: a preliminary study. Am J Gastroenterol 2000;95:326–7.

4. Miyaguchi S, Ebinuma H, Imaeda H, Nitta Y, Watanabe T, Saito H,

et al. A novel treatment for refractory primary biliary cirrhosis?

Hepatogastroenterology 2000;47:1518–21.

5. Dohmen K, Mizuta T, Nakamuta M, Shimohashi N, Ishibashi H,

Yamamoto K. Fenofibrate for patients with asymptomatic primary

biliary cirrhosis. World J Gastroenterol 2004;10:894–8.

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Best regards,

Dave

(father of (20); PSC 07/03; UC 08/03)

>

> Dave, You wrote that son'd ALT and AST came down with medication

but you are still trying to get his ALP down by other means. If it

is OK with you, can you share with me what is being tried to get his

ALP down?