Læknablaðið : fylgirit - 01.08.1978, Síða 17

Læknablaðið : fylgirit - 01.08.1978, Síða 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
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