Læknablaðið : fylgirit - 01.08.1978, Page 17

15
months of treatment. However, many
stones measuring < 15 mm in diameter
will show at least some signs of dissolving
within 12 months. Indeed, in our own
unit, some 90% of patients with radio-
lucent gallstones which measured <15 mm
in diameter who took at least 13 mg CDCA
Kg-1 day-1 and who achieved an unsaturat-
ed bile as a result of treatment, had shown
partial gallstone dissolution by one year.
In patients who do not respond in this way
one must ask about patient compliance in
taking the medication prescribed. One
should also critically re-examine the X-rays
to assess gallbladder function and to look
for evidence of calcification in the gall-
stones. If the stones have not dissolved
after 12 months treatment provided that
the patient is agreeable (most are since
they usually feel well during cheno-
therapy), it is probably worth continuing
therapy for up to 2 years. After that,
very few patients with stones which
initially measured < 15 mm in diameter
who have not already done so, will show
evidence of gallstone dissolution. If there
have been good indications for treatment
in the first instance, it may occasionally be
justifiable to continue CDCA for longer
than 2 years in patients with large gall-
stones.
SELECTION OF DIET
In non-obese gallstone patients, we
usually offer no particular dietary advice.
However, there is some experimental and
preliminary clinical evidence that the
effect of CDCA on bile lipids may be
enchanced by a low-cholesterol diet. As
yet, this evidence is too limited to re-
commend the wide-spread use of a low
cholesterol intake when treating gallstone
patients with CDCA.
In obese gallstone patients, it seems
sensible (on general medical grounds) to
recommend weight reduction by dietary
means. However, the results of one preli-
minary study suggest that during active
weight reduction in obese individuals,
there is actually an increase in biliary
cholesterol saturation. Recent studies from
our own unit in patients with gallstones
have not confirmed this observation; on
the contrary, they have suggested that
weight reduction decreases the saturation
of bile with cholesterol which should
potentiate the beneficial effects of CDCA
on bile lipid composition and on gallstone
dissolution. However, the bile lipid re-
sponse to weight reduction is unpredictible.
SELECTION OF „DRUG“ — CHENO
OR URSO?
Ursodeoxycholic acid, the 7 P epimer of
CDCA, differs from its big brother CDCA,
in only one respect — the hydroxyl group
in the 7 position is in the P rather than in
the « position.
UDCA has been used as a choleretic in
Japan for many years but in 1975, Makino
and colleagues first reported its use as a
cholelitholytic agent. Recent reports (1977)
from Japanese workers and from several
European groups (including our own) have
confirmed that:
1. Like CDCA, treatment with UDCA pro-
duces bile unsaturated in cholesterol
and dissolves gallstones.
2. UDCA probably works by the same
mechanism as CDCA — that is by reduc-
ing hepatic cholesterol synthesis (and
hence biliary cholesterol secretion)
through its inhibitory action on the rate-
limiting enzyme controlling cholestero-
genesis — HMGCoA reductase.
3. Although more expensive to manufac-
ture than CDCA, UDCA seems to be as
effective as CDCA in 50—66% the dose.
4. Unlike CDCA, UDCA does not cause
hypertransaminasaemia (seen in ap-
proximately 30% of patients given
CDCA).
5. UDCA again differs from CDCA in that
it causes little or no diarrhoea — a
dose related phenomenon seen in some
40% of patients taking CDCA.
In spite of the apparent advantages of
UDCA over CDCA, UDCA’s development
is about 5 years behind CDCA and world-
wide experience with UDCA treatment of
patients with gallstones is extremely limi-
ted. It seems likely, therefore, that for the
forseeable future there is room for the