618 HEPATOLOGY Elsewhere HEPATOLOGY

in uitro and in uiuo effects, on one hand, and the effects on protoscolices, the “fertile” form of the larva, on the other, have previously been observed with other compounds such as cyclosporin A (M. Liance, Personal communication). The severity of the human disease is mainly due to the development of “sterile” cysts and to the cellular immune reaction of the host that leads to irreversible fibrosis (8, 9). Therefore an ideal drug must be able to prevent larval growth by killing protoscolices and the germinal cells of the larva rather than merely by reducing their pro- liferative potential. The protoscolicidal effect is im- portant epidemiologically in interrupting the parasite cycle.

Are there benefits in using the two agents together? Unfortunately, m e d i d treatment of wild rodents is not possible. However, trials for the treatment of foxes, the definitive hosts, using bait that contains praziquantel, which is highly effective against the adult form of E. rnultilocularis, are currently in progress in Southern Germany (W. Franck, Personal communication). Obvi- ously, better antiechinococcal chemotherapy is needed because the article under discussion offers little hope that E. multilocularis will respond to currently available agents.

The ultimate therapeutic possibility in human AE has been orthotopic liver transplantation (OLT) since 1986 (10). Of the 60 liver transplantations performed at our center, 18 were carried out for AE. This is the first large series of transplantations performed in this disease. Despite the fact that classical contraindications to transplantation were present, the 1-year survival rate after OLT for AE is 70%, which is only slightly lower than the 85% observed after transplantations performed for other diseases. The longest survival time so far is 3 years. However, in half these patients, OLT was only a palliative procedure because other organs were already involved. Little is known about the evolution of metastatic AE in patients receiving immunosuppression. Preliminary results of the effects of cyclosporin A in experimental AE suggest that it does not have antiparasitic properties, but, in fact, it appears to stimulate larval growth (8, 9). A recent observation that suggests recurrence of AE in the transplanted liver (de la Guillaumie B, Personal com- munication) may be the clinical counterpart of some of our experimental observations. Despite the theo- retical risks of prolonged immunosuppression, we have not observed recurrence of AE in any of our 18 transplanted patients (10).

DOMINIQUE VUITTON, M.D. Department of Internal Medicine 25030 Besancon Cedex France

REFERENCES 1. Miguet JP, Bresson-Hadni S. Alveolar echinococcosis of the liver.

J Hepatol 1989;8:373-379. 2. Etievent JP, Vuitton D, Allemand H, Weill F, Gandjbakhch I,

Miguet JP, Cabrol C. Pulmonary embolism from a parasitic

3.

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10.

cardiac clot secondary to hepatic alveolar echinococcosis. J Cardiovasc Surg 1986;27:671-674. Eckert J, Burkhardt B. Chemotherapy of experimental echinococ- cosis. Ada Trop 1980;37:297-300. Rausch RL, Wilson JF, McMahon BJ, O’Gorman MA. Conse- quences of continuous mebendazole therapy in alveolar hydatid disease with a summary of a 10 year clinical trial. Ann Trop Med Parasitol 1986;80:403-419. Davis A, Pawlowski ZS, Dixon H. Multi-centre clinical trials of benzimidazole carbamates in human echinococcosis. Bull WHO

Liance M, Bresson-Hadni S, Vuitton D, Bretagne S, Houin R. Comparison of the viability and developmental characteristics of Echinococcus rnultilocularis isolates from human patients in France. Int J Parasitol 1990;20:83-86. Taylor DH, Morris DL. In uitro culture of Echimoccus rnultiloc- ularis: protoscolicidal action of praziquantel and albendazole sulphoxide. Trans R Soc Trop Med Hyg 1988;82:265-267. Vuitton DA, Guerret-Stocker S, Carbillet JP, Mantion G, Miguet JP, Grimaud JA. Collagen immunotyping of the hepatic fibrosis in human alveolar echinococcosis. Z Parasitenkd (Parasitol Red

Vuitton DA, Bresson-Hadni S, Laroche L, Kaiserlian D, Guerret- Stocker S, Bresson JL, Gillet M. Cellular immune response in Echinococcus rnultilocularis infection in humans. 11. Natural killer cell activity and cell subpopulations in the blood and in the periparasitic granuloma of patients with alveolar echinococcosis. Clin Exp Immunol 1989;78:67-74. Gillet M, Miguet JP, Mantion G, Bresson-Hadni S, Becker MC, Fkmget C, Christophe JL, et al. Orthotopic liver transplantation in alveolar echinococcosis of the liver: analysis of a series of six patients. Transplant Proc 1988;20:573-576.

1986;64:383-388.

1986;72:97-104.

BILIARY TRACT DISEASE IN AIDS: AIDS VS. NONAIDS

Cello J. Acquired immunodeficiency syndrome cholan- giopathy: spectrum of disease. Am J Med 1989;86:539- 546.

ABSTRACT Endoscopic retrograde cholangiopancreatography

(ERCP) was performed in twenty-six AIDS patients to evaluate either abdominal pain mggemtive of biliary tract disease, fever, serum alkaline phosphatase ele- vation, or a combination of these findings. Twenty patients (77%) had abnormal cholangiograms and four distinct patterns were identified: (1) papillary stenosia (n = 3); (2) sclerosingcholangitis (n = 4); (3) sclerosing cholangitis with papillary stenoeis (n = 10); and (4) long extrahepatic bile duct strictures (n = 3). Am- pullary biopey and culture identified an AIDS-related pathogen (CMV, MAI and cryptosporidium) or malig- nancy (lymphoma, Kaposi’s sarcoma) in eleven pa- tients (66%). No features differentiated patients with normal from patients with abnormal cholangiograms. Noninvasive biliary tract imaging studies (CT, ultra- sound), however, showed ductal dilation in 76% of patients with abnormal cholangiograms compared with 16% in those with normal cholangiograms (p < 0.001). Endoscopic ephincterotomy (ES) in 12 pa- tients with either papillary stenosis or the combination of sclerosing cholangitis and papillary sten& pro- duced a sienificant reduction in right upper abdominal pain, although serum alkaline phosphatase continued to increase (mean follow-up = 3.8 months). Ten of the 12 patients undergoing ES had sclerosing cholangitis, perhaps explaining this lack of response of the serum alkaline phosphatase. Of the 12 patients who had ES, five died of AIDS-related complications within nine

Vol. 12, No. 3, 1990 HEPATOLOGY else when^ 619

months of the procedure (a mean of 4.8 months), four were loet to follow-up by four months, and three were alive at 12 months. Of the eight patients who did not have ES, five were alive at one to six months and three died within five months (mean 1.7 months) after the procedure. This paper expands our knowledge of biliary tract abnormalities in Ew-infected individuals and mggests that ES may improve biliary tract 8880- ciated abdominal pain.

COMKENTS

Sclerosing lesions of the biliary tract are multifac- torial in origin (1). Primary sclerosing cholangitis (PSC) appears to be an immunological disorder, and biliary tract sclerosis has been reported in a wide variety of disorders, including histiocytosis X, sarcoidosis, ulcer- ative colitis and Crohn's disease. It also occurs after injection of scolicidal solution into the bile duct, after hepatic artery embolization or 5-fluorodeoxyuridine infusion and with congenital and acquired immunode- ficiency states, such as dysgammaglobulinemia and graft vs. host disease (1). AIDS is the latest immunological disorder to be associated with sclerosing lesions of the biliary tract. AIDS cholangiopathy represents a spec- trum of disorders of multiple etiologies. It probably is not due to HIV per se but rather to the resultant immunodeficiency state after infection with the virus. AIDS cholangiopathy has been reported in intravenous drug users, transfusion recipients, male homosexuals and subjects with HIV-2 infection (2), although it most often appears to be a result of opportunistic pathogens, particularly cryptosporidium and cytomegalovirus. Cryptosporidium has also been reported to cause scle- rosing cholangitis in congenital immunodeficiency (3). Cytomegalovirus is commonly identified in ampullary biopsy specimens (5 of 12 in this series) and may induce a vasculitis with subsequent ischemia, ulceration and warring (4) of the bile duct epithelium. This sequence has been reported in the biliary scarring after liver transplantation (5) and also has been identified in autopsies of patients with AIDS cholangiopathy (2, 4).

The cholangiopathy of AIDS is clearly distinct from that of PSC. In AIDS sclerosing cholangitis intrahepatic ducts show narrowing and beading as in PSC, but unlike PSC common bile duct dilatation, papillary stenosis and bacterial infection also occur. Histological changes of the bile duct in AIDS cholangiopathy reveal chronic inflam- mation with focal mucosal ulcerations, whereas the liver exhibits distorted interlobular bile ducts and portal fibrosis. Many of the features of the papillary stenosis seen in this syndrome are similar to sphincter of Oddi dysfunction, including a dilated biliary tree, delayed contrast drainage, biliary-type symptoms and abnormal liver tests. Manometric studies have not been reported in this situation, but the relief of pain, improved contrast drainage and decreased size of the biliary tree after endoscopic sphincterotomy suggest that such functional abnormalities may occur.

The evaluation of AIDS patients for cholangiopathy is similar to that in non-HIV-infected individuals. In any AIDS patient with fever, right upper quadrant pain and

cholestatic liver tests, the diagnosis of acalculous chole- cystitis ( 6 ) should be considered because it has a significant mortality (7) . Biliary tract disorders that are not HIV specific (i.e., gallstone disease) can also occur in the presence of HIV disease and should not be forgotten. Bile duct imaging studies should pre- cede endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholestatic liver tests, and, if normal, suggest that a liver biopsy may be more helpful than endoscopy. Biliary tree dilation is an indication for ERCP, at which time ampullary biopsies (for his- tology and culture) and bile aspiration (for cytology, cytomegalovirus culture and examination for parasites) should be done. ERCP should be considered in patients with normal imaging studies if the liver biopsy specimen suggests (and hopefully not) extrahepatic obstruction. As with many clinical studies exploring new territories, more questions are raised than an- swered. What is the prevalence of AIDS cholangiop- athy? What is the role of papillotomy in the various subgroups of AIDS cholangiopathy? Do patients with papillary stenosis alone do best? Should asymptomatic patients with dilated ducts have a papillotomy? The role of endoscopic sphincterotomy as therapy for AIDS cholangiopathy and as a means of prolonging survival is yet to be determined.

DOUGLAS SIMON, M.D., F.A.C.G. Bronx Municipal Hospital Center Albert Einstein College of Medicine LAWRENCE J. BRANDT, M.D., F.A.C.G. Montefiore Medical Center Albert Einstein College of Medicine Bronx, New York 10467

REFERENCES 1. Sherlock S. The syndrome of disappearing bile duds. Lancet

2. Roulot D, Valla D, Brun-Vezinet F, Rey M, Clavel F, Degott C, Guillian J, et al. Cholangitis in the acquired immunodeficiency syndrome: report of two cases and review of the literature. Cut

3. Davis J, Heyman M, Farrell L, Kerner J, Kerlan R, Thaler M. Sclerosing cholangitis associated with chronic cryp~poridiosis in a child with congenital immunodeficiency disorder. Am J Gastro- enteml 1987;82:1196-1202.

4. Margolis S, Lonig C, Soave R, Govioni A, Mouradian J, Jacobson I. Biliary tract obstruction in the acquired immunodeficiency syn- drome. Ann Intern Med 1986;105:207-210.

5. Martineau G , Porter K, Corman J, Launois B, Schroter G, Palmer W, Putnam C, et al. Delayed biliary tract obstruction after orthotopic liver transplant. Surgery 1972;72:604-610.

6. Blumberg R, Kelsey P, Perrone T, Dickerson R, LaQuagha M, Ferruci J. Cytomegalovirus and cryptosporidium associated acal- culous gangrenous cholecystitis. Am J Med 1984;76:1118-1123.

7. LaReJa R, Rotherberg R, Odom J, Mueller S. The incidence of intra-abdominal surgery in acquired immunodeficiency syndrome: a statistical review of 904 patients. Surgery 1989;105:175-179.

CORTICOSTEROJD THERAPY OF ALCOHOLIC HEPATITIS: HOW MANY STUDIES WILL IT TAgE?

Carithers RL Jr., Herlong HF, Diehl AM, Shaw EW, Combes B, Fallon HJ, Maddrey WC. Methylpred- nisolone therapy in patients with severe alcoholic hep-

198;2:439-496.

1987;8: 1653-1660.