panel discussion of the symposium

Panel Discussion of the Symposium

DR. AKENHEAD (Moderator): Dr. Chahners, we have some questions related to your Korean study. I)id not your patients stay in bed for 10 or 12 clays before the ad lib routine was invoked? A nurse who helped care for your hepatitis pa t ients - -who were kept at full, strict bedrest-- has stated that these patients quite often got out of bed, went to the bathroom, etc. Are you sure these patients did not get tip periodically as alleged? If they (lid get up, how valid are the conclusions you have drawn from your study? Da. CHAL-~ERS: Patients came to the Hepatitis Center in Kyoto, Japan, 11 days after tile onset of their illness. On the average, their illness was undiagnosed for 6 days, and 5 more days elapsed before they were trans- ferred to the center. They probably were at fairly complete rest (luring most of that time, but transportation by litter, Jeep, bus, and air is certainly not equivalent to strict bedrest in the hospital. Our study hegan 5 or 6 days after the diagnosis was made and that is when ad lib rest was begun. In order to be sure that the patients who were supposed to be staying in bed actually did so, we had a system of bed checks in which, six times a day, someone on the staff would make rounds on a unit and record whether each patient was, in fact, in bed or walking or otherwise breaking orders. We had fairly good control of the bed rest patients because they were told that they had to stay in bed or they would get cirrhosis, and that all sorts of dire things would happen to them. They were warned the first time, and the second time their pants were taken away, so that if they did get up and walk to the b~ithroom, they could be easily identified. They were allowed one trip to the bathroom per day to move their bowels, and they took a shower twice a week. The bed check data did show that about 10 per cent of the bed rest patients were, in fact, not flat on their backs throughout the course, but 90 per cent were, and in contrast, none of the ad lib patients were in bed all day after the first week. So there still was a striking difference between the two groups. D ~ . AKENHEAD: There is a related question: We understand what is m e a n t by strict bed rest, but what is meant by ad lib bed rest? Don' t you really mean that the patients who were very ill did adhere to bed rest programs on their own and the patients with milder cases engaged in

260 Amer;can Journal of Digestive Diseases

P A N E L D I S C U S S I O N

greater activity? If so, bed rest did play a part in the t rea tment of your ad lib group. DR. CHALMERS: This is correct. T h e patients who felt sick enough to stay in bed stayed there. However, within the first day of admission to the hospital, the majori ty were up. All the patients, within a week of admission to the hospital, were up more than the usual bed rest regimen prescribed, but they were confined to their ward and required to rest in bed for 1 hr. after each meal. One should not interpret from our study that patients should go to work or move around the house too much. No mat ter what the degree of jaundice, if the pat ient feels like being out of bed, it is all r ight for h im to lead a mildly ambula tory existence. I t may be advantageous from the s tandpoint of avoiding bed rest disease. DR. A~ENHEAD: Dr. Baggenstoss, do you think that infectious hepatit is may proceed to a lesioia that appears morphological ly similar to Laen- nec's cirrhosis? If so, how often? Also, does an attack of viral hepatit is ever result in the morphologic equivalent of Laennec 's cirrhosis? DR. BAGGENSTOSS: Ill nlost cases in which cirrhosis arises after a bout of hepatitis, postnecrotic cirrhosis will develop. I have seen a few instances, however, which I could not have distinguished from Laennec 's cirrhosis had I not known the history. Hence, it seems to me that rarely we are confronted with a gross and histological picture that is indist inguishable from Laennec's cirrhosis. DR. AKENHEAD: IS alcohol an hepato toxin in the presence of adequate nutrit ion? DR. BACGENSTOSS: I do not believe I can answer that question. I am not sure that anyone can. I assume that it is not. Ashworth and also Chaik- off and co-workers, however, have concluded that alcohol can be toxic to the liver in rats and dogs when an adequate diet is maintained. DR. AKENHEAD: Dr. \Varren, when do you do portacaval shunts in the presence of portal hypertension with varices--as prophylaxis or as an emergency measure dur ing bleeding, or as an elective procedure after bleeding? What do you believe is the value of shunt ing procedure in the t reatment of ascites? DR. WARREN: We have just started a program of so-called prophylact ic shunting. Unti l now, only patients who had esophageal varices and who had bled were considered for portacaval shunt. After we obta ined data indicating that one may actually improve the circulatory status of the liver in some cases, we set up various criteria for the selection of patients for operat ion before they have bled. As of this time, we consider those persons candidates for shunt ing who have a histological diagnosis of cirrhosis on needle biopsy, who have proved esophageal varices (or intractable ascites), and who have a definitely elevated wedged hepatic

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C U R R E N T G A S T R O E N T E R O L O G Y

venous pressure determination preoperatively. More recently, another influencing factor is the preoperative hepatic blood flow. If this is diminished by 50 per cent or more, we are relatively certain that a shunt will not greatly damage the liver. In other words, these fall into the group of patients who have approached reversal or have already reversed their flow. In this particular group, shunting will not damage the liver hemodynamically but will improve it. As for shunts for emergency control of bleeding, we believe that they are better than transesophageal ligation of the veins. We prefer to control the bleeding with esophageal compression if possible and then do a shunt at an elective date. How- ever, there are patients who are well until the time they bleed. For example, a person may be working daily and suddenly have a massive

hema temes i s for which he is quickly hospitalized. In these patients, we think that emergency shunt is the procedure of choice. However, if there is evidence of a recent bout of alcoholism or acutely deteriorating liver function that is complicated by bleeding, we are more loath to operate. \Ve have clone five emergency shunts, with one death.

For ascites, the side-to-side shunt is definitely preferable. I see no reason to do it early in the course of the disease. It should be done only in persons who have had an adequate trial of therapy and have become resistant to lnedical treatment. However, if it needs to be clone, the shunt will control ascites in all patients, contrary to public opinion. Dr. C. Stuart XVelch of Albany, N. Y., has had I00 per cent freedom from ascites in his patients who survived operation. Likewise, with the side- to-side portacaval shunt, our patients have had complete remission of ascites fiom the moment of operation onward.

DR. AKV, XHWAD: I have great difficulty finding patients with portal hypertension and bleeding on whom surgeons are willing to operate. Are their criteria for safe operation too strict? In the meantime, my patients are dying of henmrrhage. Do yon want to express s.ympathy on this?

DR. \VARREN: I certainly do express sympathy. This, however, is not the condition at Charlottesville; it is just the opposite. I do believe that there are times when surgery is not indicated. I don ' t think one shouht operate on a dying man and kill him at operation just because someone will say, "\Ve didn ' t exhaust every hope." There have been patients, ho~eveJ; ~rho came in with ascites, coma, severe jam~dice, and hemor- rhage, in which every method failed anti on whom we operated just before they died. lVe have lost 2 patients in this so-called "salvage" group. I wouldn ' t blame anybody for not operating. I think Dr. Linton's state- ment that he feels that persons who have bled from esophageal varices are, in general, candidates for surgery is true. It 's the question of getting

262 American Journal of Digestive Diseases


them into opt imal state tor surgery and, of course, there is a great variety of opinion as to when that is. DR. AKF-','HEAD: Dr. Davis, BSP retent ion was studied in some of your patients with considerable degrees of hyperbi l i rubinemia . Do you think the BSP is valid in such instances? DR. I)avIs: T h a t was the general idea. The re is no question, of course, that the BSP can be accurately measured in the presence of hyperbili- rubinemia. T h e colorimeter distinguishes very easily with the proper filter between bi l i rubin and BSP, and it was our a t tempt to show that, in these special cases of acute hepatitis at the height of jaundice the level is considerably higher than in those instances of extrahepat ic ob- struction. Sipce the experts are now able to measure the excretion and the circulation of bromsulphale in metaboli tes as well as unmetabol ized BSP, a much more accurate assessment is available of the metabol ism of BSP by the liver with severe parenchymal damage and the obstructed liver with good parenchyma; such data should be of even greater value. De. AKEXt~F..aD: Dr. Hoffman, does the degree of severity of hepatic damage correlate at all with the pat tern of glucuronide pigments in the serum?

DR. HOFF.MAN: T o a certain extent, there is some informat ion to suggest that it does, but I recently saw some figures gathered serially from a pat ient with severe hepatitis who ult imately died after a short fuhninat- ing course and in whose serum at all times, there was an appreciable proport ion of diglucuronide. In other words, the fatal terminat ion of liver disease wasn't accompanied by a total loss of the ability to conjugate bil irubin. In our experience, studying pigment patterns in the over-all group of patients with liver disease, patients with fatal hepatit is had the lowest levels of diglucuronide in the serum. But a dis turbing question t o some people is why patients who die of liver disease cont inue to be ahle to conjugate. T h e problem is more complex than that. I)R. AKFNm~AD: Dr. Ca ver, what is the point of action or mechanism of action of A C T H or corticosteroids used in the t rea tment of liver disease? DR. CArt:R: We have not obtained as good results in patients receiving A C T H as we have in patients taking corticosteroids--cortisone, Predni* sone and Medrol, for example. I think this is due to a variety of factors. T h e preparat ions we use now can be given in smaller doses and do not result in salt retention. The re are probably only a few ways in which they work: first, by cutt ing down on the inf lammatory reaction; second, by possibly prevent ing granuloma formation; and third, through an effect on circulation. Beyond that, 1 don' t believe any other informat ion

is available.

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DR. AKENnEAD: DO you use the spironalactones in ascites and if you do, do you feel the aldosterone antagonist alone is effective or do you, I presume, use it with Diuril? DR. CAYER: \Ve have had little experience with spironalactones. I t is felt by some that one of the actions of cortisone, hydrocortisone, and Medrol is the inhibi t ion of aldosterone. We have used the steroids effectively in conjunct ion with Diuril and Hydrodiur i l to promote diuresis.

DR. AKENHEAD: Do you feel that the 2-4 gin. of Neomycin are adequate? Up to 12 gin. has been advised.

DR. CAYER: We have used the smaller dosage. At onset, the material was not easy to obtain and was quite expensive in those patients being maintained on long-term therapy. We have come to believe that the smaller dosage is adequate.

DR. AKFNHEAD: Dr. Baggenstoss, what do you think of Dr. Warren 's work and what is the viewpoint at Rochester [Mayo Clinic] in reference to shunts? DR. BA(;GENSTOSS: Of course, I am very proud of Dr. Warren 's work; it substantiates the ideas that we presented some years ago by reconstruction of the regenerative nodule in the cirrhotic liver, indicating that the regenerative nodule by its growth, to some extent, compresses the sub- lobular veins. Of course, this might not appear to be so important at first consideration, but when it is realized that in a cirrhotic liver there are practically no central veins and that almost all the veins that remain are compressed and distorted, the hemodynamic significance of this altered reconstruction of the liver is seen to be important . As to the consensus at Rochester, concerning shunts, Dr. Warren knows more about that question than I do. DR. AKENHEAI): Do you care to comment , Dr. Warren? DR. WARR}:N: They have just published their work on shunts and have come to the conclusion that, a l though they had considered an end-to- side portacaval shunt prelerable, in analyzing 5-yr. survivals, the end-to- side portacaval shunt has resulted in the lowest percentage. The inter- mediate group were those who had only splenectomy and a high incidence of recurrent bleeding, but who still live longer, and the best g r o u p - - a b o u t 75 per cent survival--consisted of those who have had splenorenal shunts that again have a high incidence of recurrent bleeding. I think this bears out our hypothesis that preservation of the portal vein benefits the liver. Even those who have continued episodes ot bleeding appear to be better. DR. AKI~:NHEAI): Dr. Baggenstoss, is the biopsy histology in drug-induced



jaundice sufficiently specific to rule out other surgical and medical forms of jaundice? DR. BAGGENSTOSS: NO, the histological aspects of a specimen taken for biopsy certainly are not specific enough to rule out the forms mentioned. I have been misled too frequently to be able to say anything else. Strangely enough, we often confuse the changes caused by thorazine with those of obstructive jaundice ra ther than with those produced by toxic hepatitis. Drug-induced jaundice has many of the features of obstruct ion of the extrahepatic bile ducts and can be a very dilficult p roblem if you do not have the guidance of the history. Some other drugs, as Dr. Chalmers mentioned, also produce conditions that miniic viral hepatitis. For instance, Dr. Popper, a year ago, showed me some sections of tissue affected by Marsalid toxicity that were very similar to sections showing viral hepatitis. In our r'ecords are some sections of tissue from patients who received cinchophen; these sections originally were classified as representing cinchophen hepatitis, but now, if I were to study them, I could not distinguish them from sections showing viral hepatitis. Cer- tainly, in many instances, the reaction of the liver is l imited and by no means are the changes always pa thognomonic of the type of injury re- sponsible. DR. AKENHEAD: Dr. Davis, is intravenous cholangiography dangerous? What are the number or percentage reaction, percentage deaths, etc.? Dm DAvls: I t is relatively safe. Actually, I know of no deaths. A few instances of moderate reaction, I think, are on record. Certainly, if one gives the dye in very much of a hurry, one is certain to get a significant amount of nausea and sonic blood pressure drop, with pallor, etc., but we have not had any really significant reactions in our experience. I believe that generally mirrors the experience the country over. DR. AKENHEAI): Dr. Chalmers, a Swedish physician demonstra ted a ra ther close parallelism between severe outbreaks of hepatit is and subsequent cirrhosis over 30-40 yr. Wha t do you make of this? DR. CHAL.XZERS: I cannot explain the Scandinavian experience except to say that the epidemic has not been seen since. These were not cases where patients developed hepatitis and then, 5 or 10 yr. later, turned out to have cirrhosis. They were people whose acute illness was the first stage of a progressive disease from which they died in 1-2 yr. This, I think, has always been the trouble in our in terpreta t ion of the etiologi- cal importance of a preceding hepatitis. I t is difficult to distinguish between an episode of epidemic viral hepatitis some time in the past, and an episode of jaundice that is a part of the natural history of the progressive disease of unknown etiologly called nonalcoholic cirrhosis. DR. AKENHEAD: Dr. Warren, since the side-to-side shunt appears to ira-

New Ser;es, Vol. 6, No. 3, I?61 ~ 6 ~

C U R R E N T G A S T R O E N T E R O I . O G Y

prove liver blood flow, does it appear to you that the shunt has any place in the treatment of liver insufficiency without marked portal hypertension? Also, do you feel Dr. Childs' double shunt has anything more to offer in ascites? DR. WARREN: \Ve don ' t feel that the shunt has anything of significance to add unless there is a definite portal hypertension. We have operated on 1 patient, one of the so-called salvage cases that 1 mentioned, who had been in coma about 13 times and had the lowest recorded blood flow that we have seen. We operated on him in an attempt to improve his total hepatic blood flow al though he did not have evidence of portal hypertension at the time and had no esophageal varices. At operation, he had no portal hypertension and had spontaneously decompressed through a huge collateral vessel. Of course, the shunt in that respect has nothing to offer because there was no question of varices. So the answer to the first question would be no.

The double-shunt technic of Childs to which you refer has been most recently studied by Dr. Will iam McDermott in Boston, and I can see absolutely no physiological difference between it and the side-to-side portacaval shunt. They did not measure intrahepatic pressures so there are no comparative data on this aspect. However, in every instance, we have lowered that portal vein pressure to normal. We have had no instance of closure of a shunt except for 1 patient on whom a resident did his first portacaval anastomosis. This shunt closed immediately, the patient hemorrhaged, developed ascites, and was reoperated on as an emergency with reconstruction of the anastomosis. He has subsequently done well with normal catheterization findings. So unless there is some other advantage of which I am unaware, I can see no real reason for making two anastomoses. DR. AKENHEAD: Dr. Cayer, what are the signs of hepatitis going into acute yellow atrophy, and how do you treat a patient with so-called acute yellow atrophy or fuhninat ing hepatitis?

DR. CAYER: The great majority of patients who have viral hepatitis have a mild disorder lasting 4-6 wk. with perhaps a day or two of anorexia, nausea, or vomiting. They are relatively afebrile and improve rapidly, with a fall in the van den Bergh test result that usually doesn't go above 6 or 8 mg .~ , and do perfectly well. The patient who becomes progres- sively more anorexic after a period of 10-I4 days, who has a van den Bergh result that exceeds 10 mg.% that continues to rise, who becomes confused or apathetic or goes into coma with deepening jaundice, and who has a rapid decrease in liver size, is the patient who is developing subacute or acute yellow atrophy. We wouhl try to manage that patient



with intravenous glucose, maintenance doses of accessory vitamins, and steroids and antibiotics. DR. WARREN: Dr. Akenhead, regarding the question ol operat ion in the absence ot portal hypertension, if there are varices, even though there is a normal portal pressure, patients can still bleed to death from those veins. Other than that, there is no indication. DR. AKE.Xm~AD: Dr. Davis, are you still measuring splenic pressure, and what help might that and splenoportography offer in differential diagnosis of carcinoma, parenchymal disease, and so forth? DR. Davis: l/Ve are still measuring splenic pressures. They are of benefit on occasion in differential diagnosis. For instauce, in a carcinoma of the pancreas in perhaps 15 per cent of instances, elevation of the intra- splenic pressure exists by virtue of invasion of the splenic vein from the tumor in the body or tall of the pancreas. Splenopor tography is of considerable value f rom the same s tandpoint and may also be of value in the diagnosis of space-occupying lesions fur ther on in the area of portal distr ibution in the liver. DR. CHALMERS: Dr. Akenhead, I 'm worried about that question about precautions. I hope I d idn ' t give the impression that I did not think patients with viral hepatitis should be on precautions in terms of not t ransmit t ing the virus from their stools to the personnel and other patients. All I meant to imply was that, a l though their stools are infectious, so are everybody's and, therefore, the same precaut ion should apply to all people in terms of washing hands in the hospital. I think this is especially impor tan t now in these days of hemolytic staphylococcus aureus; we've gotten too far away from the idea that infections are trans- mitted from patient to pat ient because we've singled out 1 or 2 patients and said, "These are the ones you have to be careful of." DR. AKENttEAD: T o summarize briefly, I think Dr. Hoffman has removed the mystery more or less of the van den Bergh test, and he has told us why bile is excreted or not excreted in the urine; he has told us why the van den Bergh test is direct and why it is indirect. He has suggested that differential separation of the mono- and diglucuronides might be of some practical value and he has given strong suggestions as to the etiology of Gilbert 's disease, jaundice of the newborn, and other assorted conditions.

We have had our ideas on the pathogenesis of cirrhosis shaken just a little and have heard the evidence for possible inclusion of postnecrotic cirrhosis among the au to immune diseases.

Dr. Chahners has given us hope that electronmicroscopy might solve some of the problem of active and smoldering virus etiology, has stressed prevention of homologous serum jaundice, and has re-raised--resur-

New SerieL Vol. 6, No. 3, 1961 267


rected, i might say- - the question of advisability and necessity of long periods o[ bed rest in hepatitis. I don ' t think he has even int imated that bed rest in the very ill pat ient is a bad thing.

We have been instructed in the principles of t reatment of hepatic conla and have heard a very scholarly exposition on corrective surgery for portal hypertension.

Finally, Dr. Davis has told us to use everything in evaluation of the pat ient for surgery, that there is no easy way, and that it's still neccssary to think.

268 American Journal of Dicjestiva Diseases

panel discussion of the symposium

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