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Pathology and Immunology of Clonorchis Sinensis Infection of the Liver TSIEH SUN, M.D

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Pathology and Immunology of Clonorchis Sinensis Infection of the Liver TSIEH SUN, M.D ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 14, No. 3 Copyright © 1984, Institute for Clinical Science, Inc. Pathology and Immunology of Clonorchis sinensis Infection of the Liver TSIEH SUN, M.D. Department of Laboratories, North Shore University Hospital, Manhasset, NY 11030 and Department of Pathology, Cornell University Medical College, New York, NY 10021 ABSTRACT The existence of clonorchiasis cases among the Asian immigrants and the major clinical and pathologic features encountered in those patients is emphasized. Owing to the longevity of the parasite, clinical symptoms may occur long after endemic exposure. The common manifestations among the immigrants are recurrent pyogenic cholangitis and pancreatitis. The relationship between clonorchiasis and cholangiocarcinoma and the possible pathogenesis of this tumor are discussed. The specific immuno­ logic phenomenon in clonorchiasis is described. Epidemiology takes about one month for the metacer- caria to mature, when Clonorchis eggs Clonorchiasis is endemic in the Far can be detected in stools. Eggs hatch East, mainly Hong Kong, China, Taiwan, only after ingestion by a suitable snail Japan, Korea, and Vietnam.6 It was es­ host. In the snail host, the hatched mir­ timated that 19 million people were in­ acidium passes through stages of sporo- fected in endemic areas.22 However, the cyst, redia, and cercaria. The cercariae incidence of clonorchiasis dropped mark­ invade the flesh of a suitable fish host edly owing to environmental changes in and become encysted metacercariae. Ap­ recent years. In Japan, for instance, proximately 100 species of fresh water water pollution eliminates most of the fish have been incriminated as the inter­ snail hosts of Clonorchis sinensis.22 The mediate host of C. sinensis. On the other composition of manure before use in hand, the snail host of C. sinenis is more China kills Clonorchis ova in stools, thus specific: only snails of the genus Parafos- interrupting the life cycle.22 sarulus, Bulimus, Alocimua and Melan- The infection is caused by consump­ oides can act as intermediate host. Since tion of raw, infected fish. The metacer- these snails have not been found in cariae in fish flesh are released in the North America, clonorchiasis will not be­ duodenum whence the parasite migrates come endemic in the United States in along the common bile duct and finally spite of the influx of Asian refugees. stays in the intrahepatic bile ducts.23 It However, Americans may obtain clon- 208 0091-7370/84/0500-0208 $01.20 © Institute for Clinical Science, Inc. CLONORCHIASIS 209 orchiasis through long-term and short­ Pathology term visits to endemic areas.21 The long life span of C. sinensis (20 to The major pathologic findings are seen 30 years) creates a problem for the Asian in the liver. The mechanical injury immigrants. There are well-documented caused by the suckers of the parasite and cases in which the patients developed chemical stimulation by its metabolic clinical symptoms many years after products may contribute to the changes leaving the endemic area.16 Most of the of the epithelium of the bile ducts.2' The patients reported are from Hong Kong. two basic morphologic changes are ade­ Less frequently seen are patients from nomatous proliferation and goblet cell China and Korea. Laotian refugees usu­ metaplasia (figure I).6,7’8 In chronic in­ ally carry Opisthorchis viverrini rather fections, the adenomatous tissue is grad­ than C. sinensis. However, the ova of ually replaced by fibrous tissue, thus these two parasites are practically indis­ causing thickening of bile ducts which tinguishable. Accordingly, cases of clon- can be visible grossly. orchiasis are most frequently seen in The most common complication in large cities where there are many clonorchiasis is recurrent pyogenic chol­ Chinese immigrants, such as New York angitis (RPC) or oriental cholangiohepa- City,10 Los Angeles,28 and Montreal.15 titis (figure 2).6-22 This is also the most Even in South Carolina, seven to 43 important clinical finding in immigrants cases of clonorchiasis were reported an­ in North America, leading to the diag­ nually since 1978.13 nosis of clonorchiasis.1-2,717’28 Owing to F ig u r e 1. An adult C. sinensis in an intrahepatic bile duct. The sucking force of the ventral sucker (V) obviously causes mechanical injury to the ductal epithelium with resultant desquamation and superficial ulceration. Adenomatous proliferation of epithelium, as shown here, is the consequence of such damage. Hematoxylin and eosin. (X200). From Sun22 with permission. 210 SUN iâ JfWBW iBF&k.'*'' JP iBu5r M HS^aW «■ F ig u r e 2 . A case of recurrent pyogenic cholangitis showing heavy cellular infiltration of a denuded bile duct. The lumen contains inspissated bile mixed with Clonorchis ova. Hematoxylin and eosin. ( X 160). From Sun22 with permission. goblet cell metaplasia of the bile duct ep­ beyond the bile duct, causing perichol­ ithelium, the bile contains high contents angitis and periductal fibrosis. Liver ab­ of mucous secretion. This mucinous bile scess may occur if the parenchyma is in­ and the existence of the parasite and its volved by the infectious process. A ova in the bile duct cause cholestasis and postnecrotic or biliary cirrhosis may de­ furnish a favorable environment for sec­ velop on this basis; however, unlike ondary bacterial infection. The causative schistosomiasis, “pipe stem” cirrhosis is agent is usually Escherichia coli as­ never seen in uncomplicated cases. An­ cending from the intestine. The ova and other complication of RPC is stricture of bacterial colonies may thus form the the left hepatic duct which may or may nidus of an intrahepatic gallstone which not be accompanied by atrophy of the left is usually muddy. The lack of primary hepatic lobe.28 The most severe sequela stone in the gallbladder is characteristic is hepatic coma owing to extensive liver of this situation. Owing to cholangitis and damage. partial biliary obstruction, the patients Pancreatitis is another complication usually show repeated episodes of ab­ which may present as a major clinical dominal pain, fever, jaundice, and he­ manifestation in Asian immigrants.16 A patomegaly, which are typical for RPC. Chinese immigrant in New York devel­ This clinical entity can be diagnosed by oped acute pancreatitis 25 years after en­ a cholangiogram demonstrating the demic exposure.16 The patient did not re­ markedly dilated intrahepatic bile ducts spond to symptomatic therapy and with partial filling defects representing recovered only after anthelminthic stones or a mass of flukes.7 treatment. In Hong Kong, over one- The consequence of RPC is multiple. third of clonorchiasis cases had pan­ Most frequently, the infection spreads creatic involvement.4 However, the pa­ CLONORCHIASIS 211 tient may not have any clinical evidence epidemiologic statistics, i.e., cholangio­ of pancreatitis. On the other hand, clon- carcinoma is more frequently seen in orchiasis is the causative agent in 83 per­ clonorchiasis endemic areas than non-en- cent of patients with pancreatitis of un­ demic areas, and Clonorchis infection is known etiology in Hong Kong.12 This seen in 94.7 percent of cholangiocarci­ Clonorchis-related pancreatitis usually noma cases as compared to 31.7 percent develops one to three hours after a rich in a control population in Hong Kong.3 meal, which may have stimulated excess Cholangiocarcinoma has also been exper­ flow of pancreatic juice in a partially ob­ imentally produced in animals infected structed pancreatic duct, leading to au­ with Clonorchis.89 The fact that cholan­ todigestion.12 The pathology of pan­ giocarcinoma usually develops in the creatic clonorchiasis is similar to the second order intrahepatic bile duct hepatic lesion, namely, adenomatous where Clonorchis is located and that hyperplasia of ductal epithelium (figure adenomatous proliferation of ductal epi- 3).6 Squamous metaplasia is also fre­ thelim can be seen side by side with ma­ quently demonstrated and is character­ lignant changes (figure 4) is also suppor­ istic of pancreatic clonorchiasis.22 When tive of the relationship between these acute pancreatitis occurs, features of two entities. acute inflammation are present. The exact pathogenesis of cholangio­ The most grave consequence of clon­ carcinoma is still unknown. It seems orchiasis is cholangiocarcinoma.3,5,14 The likely that Clonorchis infection is only a causative role of clonorchiasis in the de­ predisposing factor by inducing prolifer­ velopment of this tumor is supported by ation of the epithelium of bile ducts.5 F ig u r e 3 . Two sections of an adult C. sinensis in a pancreatic duct which is partly denuded with maked adenomatous hyperplasia. Hematoxylin and eosin. (X50). From Sun22 with permission. 212 sun­ s' -- - * V >v> «;; ■ #:/& ■. >*• #«f F ig u r e 4 . A case of cholangiocarcinoma showing a cross section of an adult C. sinensis in the lumen of a cancerous bile duct. Note the coexistence of normal epithelium and malignant cells. Hematoxylin and eosin. (X50). From Sun22 with permission. The proliferating epithelium may be sus- which are found commonly in preserved ceptable to the action of carcinogen(s) foodstuffs in the Far East.5,14 In southern present at levels insufficient to induce China and Hong Kong, it has been found cholangiocarcinoma in non-infected in­ in salted fish and dried shrimps. Al­ dividuals. Hou has suggested that the though the pathogenesis of cholangio­ metabolic or degenerative products of carcinoma is still inconclusive, it is rea­ the parasite and/or a bile component al­ sonable to assume that the etiology is tered chemically by the parasite can be multifactorial in origin. the origin of carcinogenic substances.8,9 CZcmorc/i/s-associatedcholangiocarci- However, Flavell argues that if this is noma is characterized by prominent true, the carcinogen(s) should be accu­ mucin secretion. It is also frequently ac­ mulated in the gallbladder and induce companied by extensive fibrosis.
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