key: cord-0009085-yygerqj9
authors: Wright, Ralph
title: AUSTRALIA ANTIGEN AND SMOOTH-MUSCLE ANTIBODY IN ACUTE AND CHRONIC HEPATITIS
date: 1970-03-07
journal: Lancet
DOI: 10.1016/s0140-6736(70)91605-3
sha: ca86e971de88709ce3987975c7ff1419b1a96069
doc_id: 9085
cord_uid: yygerqj9

nan

SIR,-I am dismayed by Professor Peart's intemperate plea to kill off the Professor of Medicine (Feb. 21, p. 401).

In his haste to rush to the aid of the talented graduate, he barely touches upon the far greater need of the medical student. Perhaps being a provincial myself has made me biased. Nevertheless, I cannot help surmising that this attitude is peculiar to the London teaching-hospitals. The fragmentation of teaching in London, with its consequent remoteness from the centre of university life, seems to foster a different approach from that of the provinces, where the medical schools are more closely integrated with the parent university.

Prof. D. A. K. Black, of Manchester, in his booklet, The Logic of Medicine, has wisely pointed out that " Medicine is very much what the doctor cares to make it, being limited by his own endowments, by the opportunities which he makes or finds, and by the facts of life, as he would be in any other profession". Surely the freedom to choose grows best in a true university setting rather than in a rigid hierarchy, with its organisation men (however gifted), and the smack of the business boardroom advocated Technical variations are unlikely to be responsible for the different results, and it has been suggested that they might be due to differences in definition or aetiology.3,4 Because of increasing evidence that the Au antigen is closely related to, if not identical with, a hepatitis virus,5,6 its detection in C.A.H. supports the view that persistence of the virus may be of importance in the pathogenesis of that disease. Another hypothesis which has been widely held invokes an autoimmune disturbance. This hypothesis is based on the frequency with which immunological abnormalities such as hyperglobulinaemia, the L.E.-cell phenomenon, antinuclear factor, and an antibody reacting with smooth muscle are found in the serum of patients with C.A.H. The smooth-muscle antibody (S.M.A.) is the commonest of these, and according to some investigators shows a high degree of specificity for C.A.H.7,8 Its relationship to the Au antigen has, therefore, been examined.

Sera from patients with acute viral hepatitis, prolonged classic viral hepatitis, subacute hepatic necrosis (S.H.N.) with progression to cirrhosis, and C.A.H. of insidious onset (described previously 1), were tested for antibodies to rat smooth muscle by the indirect immunofluorescence technique of When serial specimens were tested, it was often only present intermittently, it occurred as frequently in Au-positive as in Au-negative patients, and it could be detected both early and late in the disease. In 9 patients it was present at high titre. Of 13 patients with prolonged classic viral hepatitis, only 2 had S.M.A., both at low titre, and the Au antigen was present in 6. Results in the 15 patients with subacute hepatic necrosis (S.H.N.) which had progressed to cirrhosis are of special interest. As pointed out previously,! this group shows features which may be indistinguishable from c. The possibility that S.M.A. is an antibody to the Au antigen has been examined, but this does not appear to be the case since sera containing antibody to the Au antigen do not react with rat smooth muscle by the immunofluorescent technique, and sera from patients with hightitre s.M.A. do not react with Au antigen in the immunodiffusion technique. Furthermore, absorption studies show that they are distinct.

Studies of Au antigen in patients with C.A.H. suggest the following tentative conclusions:

(1) The presence of Au antigen in the serum of patients with S.H.N. during progression to cirrhosis, and in patients with C.A.H. of insidious onset, strongly suggests that persistent infection with the Au antigen may be responsible for cirrhosis in some patients. 3 patients with Au antigen whose illness started acutely had epidemiological evidence of serum hepatitis; this supports the view that geographical differences in the prevalence of serum hepatitis may be responsible for the different results obtained. In this respect, it is of interest to speculate on the possibility that the Au antigen may be responsible for chronic liver disease and cirrhosis in parts of Africa and Asia where it has been detected at high frequency in the normal population.9 The frequent use of scarification to produce tribal markings would provide a ready method for the spread of serum hepatitis which might become chronic because of impaired immunological responses resulting from malnutrition or parasitic infection.

(2) In those patients with C.A.H. who do not have the Au antigen in the serum, the detection of S.M.A. at high titre suggests that such cases might be xtiologically distinct, or that the disease, after being initiated by infection with the Au antigen, could be perpetuated by some other mechanism such as an autoimmune process. The could readily be missed if such cases are not seen early. The absence of detectable Au antigen in the blood, however, may only mean that it is in complex with antibody or that it is sequestered in the liver, and with improved techniques it might be detected in a much higher proportion of patients. Finally finding (Jan. 10, p. 51) of cryofibrinogen in women taking oral contraceptives and their suggestion that a cryofibrinogen-screening test might be used to detect individuals with an increased risk of adverse reactions to these agents. We have detected cryofibrinogenxmia (more than 1-5 vol. %) in 6 of 9 pregnant women.!1 Cryofibrinogenaemia in individuals with " pseudopregnancy " due to oral contraceptives is therefore not wholly unexpected. The amount of cryofibrinogen detected depends on several technical factors, including the type and concentration of anticoagulants used. Heparin, in concentrations of 0-25-1-0 mg. per ml. of venous blood, gives maximum yields of cryofibrinogen, and might be preferable to oxalate or citrate for use in a screening test. STEPHAN E. RITZMANN 

SiR,-In the past few years several reports have been published providing evidence for the effectiveness of new synthetic compounds in the alleviation of parkinsonism. I have no wish to detract from the scientific value of these researches in the field of clinical pharmacology. Nevertheless it is important to remember that standard remedies such as benzhexol, properly used, rarely fail to produce striking relief in this disorder. Occasionally the benefits can be further enhanced by adding daily doses of orphenadrine. I suggest therefore that the objective in clinical research should be to answer these questions: (1) In all the patients in the group under investigation has treatment with benzhexol been pushed (in stages) to the limits of the individual's tolerance ?

(2) How does the efficacy of the new drug in an otherwise untreated patient compare with that of benzhexol (see [1] above) ?

(3) If the research-worker considers it unethical first to deprive the patient of drugs such as benzhexol, and insists on giving the new drug merely as a supplement to conventional therapy, why does he not gradually withdraw conventional treatment (benzhexol and the like) to show how much of the improvement attributed to the combined old and new drugs can be credited to the new preparation ? drug or a placebo, it may be argued that where a favourable response (further improvement) appears to be attributable to the new drug, the same benefits might have been conferred simply by increasing the dose of the preparation (or preparations) already being given as " previous treatment ". , Expressed differently, so long as the dose of " previous treatment " is less than the optimal dose there will inevitably be room for improvement in the patient's condition. The therapeutic deficit can be made good by a supplement of one or other of the " anti-parkinsonism " drugs, but it should not be assumed that the second phase of improvement reveals the specific effect of one preparationwhich happens to be a new drug. I am old enough to recall the methods of treatment in vogue in the 1920s, when postencephalitic syndromes were extremely common following the pandemic that coincided with the war of 1914-18. The conventional treatment was to give the drugs of the atropine group-usually as tincture of hyoscyamus-up to the limits of the patient's tolerance. Drug therapy on these lines was certainly effective; but I have no doubt that the introduction of benzhexol and similar compounds (about 1949) marked a notable advance because these drugs produced therapeutic effects with few undesirable side-effects. planned ventilation for general ward use. We were however disappointed that you did not refer to our recent investigation carried out in the experimental ward unit built at Hairmyres Hospital by the Scottish Home and Health Department to study this and other problems of hospital design.! Over a ten-month period we compared the nasal acquisition of staphylococci and the staphylococcal-woundinfection incidence in the experimental unit, which had controlled ventilation giving seven air changes hourly, and in two open-plan wards with natural ventilation. The three wards were staffed by the same surgical teams, and admitted patients in rotation. 1726 patients were studied. The patients in the experimental unit had a slightly reduced nasal-acquisition rate of Staphylococcus aureus as compared with the old-style wards (10-6 per 100 patient-weeks against 12-4 per 100 patient-weeks). This advantage was apparent only in patients staying less than two weeks in hospital (9-2 per 100 patient-weeks against 12-9 per 100 patientweeks) and had almost disappeared in patients staying in hospital beyond two weeks (11-4 per 100 patient-weeks against 12-1 per 100 patient-weeks).

The acquired staphylococcal-wound-infection rate was in fact higher in the experimental unit than in the control wards (24 of 446 operations or 5-6%, against 21 of 587 or 3-6%). This applied to both short-stay and long-stay patients. This confirms that the airborne route of spread of infection is only one of many to be considered.

The cost of the air-conditioning plant was E42,000, this

Summerskill