Successful treatment of Indian childhood cirrhosis

Successful Treatment of Indian Childhood Cirrhosis l‘hci~e IS 17asoi1 10 celebrate when histo~~atholo~i~ studies lead 1101onh lo successful treatulent of disease. Init also 10 its prr&nticm. The reports of l’ortiiiann el al in 1978’ aird I‘ann~r et al iu l!I79’ that the c,irrhotic 1ivt.rs of Indian childret had marked accumulations of c’opper were soon followed by treatment trials with ti-peni~illaliiirle. nv 1 !)H*/, Tanner and his Indiau colleagues wel-r ablr ‘to report the dramatic rescue from iuevitahle death of voung children with milder- f~ornls of tht. disease within ‘6 months hy the administration 01 f)e~li~iflalllitit~. The!, desc,ribed. but did not illustrate, the rc5cAution ol’thc c’liaracteristic hepatocellular IrGoris in po5ttreatnitrIit ~Aopsies. ’ In this issue of FJurtu~rr P~~fholq~, Khusnumath et al have provided the first illustrations dcmrnnentiug in sequential biopsies the restoration of normal hepntoc.ytr c‘ytology and. possiblv. even diniinishrd scxrillg after treatment. In the first penicillamine drug trials, there werta c.olltrols for both the initial group with advanced diseasr chat failed IO beuefit and for the group with milder disea\e. The great su(xess with the latter group prevented Bhusuurn~~tth et al froul enlisting a control group for their sriiall series on ethical grounds; howe\,er, in this disease, progression without treatmerit is so well dotuurruted (cmly one of 14 children in Tanner et al’s con~1x4group :;u&ved) that the combination of clinical and histologic improvement reported can be attributed onl) to the medic~ation. However, as Bhusnurmath et al point out. the posttherapy livers remain architectumlly vet7 distorrrd hy delicate fibrous septa and micronodules, ho the Ioug-tern’ (.onsequences of portal hypertension rrn~~i~~. Tlw tl;it;i on complete restoration of‘ normal ‘lr( hitecturr in the few cases reported hy TameI- et al” and in one pa’ieut reported by Bhusnurmath et al are uncertain becat~ small needle hiopsies can only hint at the status of’ the whole organ. The possibility exists of continued spontaneous remodeling once the toxic mrtal is removed by penicillamine interference with collagen cros+linking. Hhusnurrnath et al do not indicate what their intentions are regarding further treatment. After their recognition of the enormous copper cxmtent of the liver. Tanner et al looked for its source.’ Then were able to show that rural middle-class Hindus typically boil fresh milk in brass pots that often have not beeu adequately tinned. They showed that the milk ex(r’acth largt~ quantities of copper, but unfortunately not /ill<, frcml the alloy.’ This copper is bound to casein and c-an be .thsorhed from the intestines. ‘The only available physiologic route for excretion of copper is tht hrpatohiliai-y svstern, and that system is well known 10 he less act!l\e in young infants. Review of families with both affected and unaffected siblings by Bhave et al” I”ovidrd ;I reasonable explanation for the difference. 633

iti 1ha1 cluraticm of‘ hreas( f’eedilig \vas 1n11( II rcducetl amoug the infaut~ with cirrhosis. Indt~l, 111~nlost inforniativt~ data came froni two stats ot. twillc, in whit-11 lethal cirrhoaia occurred only in the c.hildrt*n fed cow’s Inilk shoi-tlv after birth. Thus, the path to preventiori is evident. If’ it is followed. the (urrent report could he the List to dot ument the benefits of penic~iffanlirie iu (‘ases of 1ndian childhood cirrhosis. There are a few case reports of a similar form of childhood micronodular cirrhosis with Mallory bodies md high copper load outside of India. In most. exposure of i&nts to Lt’ry large quantities of copper. in dl-inking water cm ried iu copper pipes has been clrrrlollstr,lted.‘.’ ()nce again, (ml>; infants were aflected, probably because 01 rhc inmatur~ty of their est.retory apparatus. Howcvcr, even in adults, the system can <)e o\-ei-whellned hv niassive c’opper loads, as in a psycholc)gic;lllv disturbe;l middle-aged wonlan, reported by Yelin et ~1, who swalIowed 275 LlS c.oins weighing 9X) g.” There- rrnlain sonle illstances of childhood cirrhosis associated with a high copper content, but no evidence of‘ Wilson’s disease OI c.hronic cholestasis and no drnlonstrable exposure to environmental sources of excess c’opper. I” Whether these patients have 21 metabolic error in a metallothiotwin remains to be determined. As the idc~l~ification of the gene for Wilson’s disease appears imminent. ’ we can expect to further dissect the potwtial mechanisms of inhortl errors responsible for copper-induc.ed toxicitv. In the nieantimc, prevention of large numbers of cas& of childhood cirrhosis by avoiding brass pots is now possihle

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