Cholangiohepatic Opisthorchiasis

　　After the eggs of Clonorchis sinensis pass through the first intermediate host (freshwater snails) and the second intermediate host (freshwater fish and shrimp), they develop into cercariae. After the living cercariae are ingested, they are activated by bile, the larvae break through the cyst wall, and enter the liver and bile ducts through the common bile duct to develop into adults. They can also reach the liver through the blood vessels or penetrate the intestinal wall, finally residing in the liver and bile ducts to develop into adults. The lifespan of adults is generally 20 to 30 years, mainly residing in the bile ducts of humans, dogs, cats, and pigs. When the number of worms is large, they can also migrate to larger bile ducts or even the gallbladder. Occasionally, adults can also be found in the pancreatic duct.

　　The degree of pathological changes in the liver and bile ducts where adult flukes reside is closely related to the number of Clonorchis sinensis infected and the duration of infection. If the number of infected worms is only a dozen to several dozen, there are often no visible pathological changes in the liver and bile ducts. If the number of parasites exceeds 100, even several thousand, due to the worms filling the intrahepatic and extrahepatic bile ducts, gallbladder, and pancreatic ducts, it can cause biliary obstruction, accompanied by cholangitis, liver abscess, pancreatitis, and other complications. The pathological changes of Clonorchis sinensis mainly occur in the small intrahepatic bile ducts, causing bile stasis due to the mechanical obstruction of the worms and the toxic effects of their metabolic products, resulting in cystic or cylindrical dilation of the bile ducts, especially in the marginal part of the left lobe. The bile duct epithelial cells show desquamation and hyperplasia, and the bile duct wall thickens due to the hyperplasia of connective tissue, with a large number of glandular hyperplasia, lymphocytes, and granulocytes infiltrating. The adjacent liver cells show fatty degeneration, atrophy, and necrosis, ultimately leading to biliary cirrhosis. The dead bodies, eggs, and desquamated bile duct epithelium of Clonorchis sinensis can become the core of calculus formation, triggering biliary tract calculi. It is reported that this disease is closely related to cholangiocellular carcinoma.

　　Clonorchis sinensis biliary disease can cause diseases such as biliary calculi, cholangitis stenosis, and cholangiocarcinoma, as follows:

　　1. Chronic or acute cholecystitis with Clonorchis sinensis

　　The damage to the body of the worm and the bile duct epithelium can easily cause biliary obstruction and bacterial infection. In the流行 area of the Pearl River Delta in Guangdong, the rate of concurrent Clonorchis sinensis infection among those hospitalized for biliary diseases is up to 75%. Clinical manifestations include abdominal pain, gallbladder enlargement, chills, fever, and obstruction jaundice caused by a large number of worms.

　　2. Biliary calculi

　　The stones caused by Clonorchis sinensis are mostly multiple pigmented stones in the intraphepatic bile ducts, which is related to the fact that the parasites often reside in medium and small bile ducts.

　　3. Cholangitis stenosis

　　The bile ducts where Clonorchis sinensis resides can undergo adenomatous or polypoid hyperplasia, recurrent cholangitis, fibrosis of the bile duct wall, leading to bile duct stenosis and obstruction. This type of stenosis is more common in medium-sized intraphepatic bile ducts. During ERCP examination for biliary obstruction caused by schistosomes, it was found that papillary intubation encountered varying degrees of difficulty, with 57.2% being benign papillary sphincter stenosis, indicating that schistosomes can cause distal biliary stenosis.

　　4. Cholangiocarcinoma

　　The incidence of cholangiocarcinoma after Clonorchis sinensis infection is significantly higher than that of non-infected individuals. The bile ducts surrounded by or connected to the tumor often contain adult flukes or eggs; histological examination shows peribiliary fibrosis, increased mucus secretion by bile duct epithelium, and adenomatous hyperplasia. The incidence of cholangiocarcinoma in Hong Kong is also closely related to schistosome infection.

　　5. Pancreatitis

　　Pancreatitis is generally caused by adult worms blocking the pancreatic duct.

　　The incubation period for cholangioclonorchiasis is 1 to 2 months. Mild infections often present no symptoms, but eggs may be found in feces.Severe infections are often due to repeated infections, with a slow onset. However, in non-endemic areas, infection can occur acutely. The main clinical manifestations in the acute phase include gastrointestinal symptoms and allergic reactions, such as loss of appetite, upper abdominal dull pain, fullness, hidden pain in the liver area, enlarged liver (especially in the left lobe), and symptoms such as fever, fatigue, dizziness, insomnia, decreased vitality, and memory loss. Occasionally, massive worms can block the common bile duct, leading to biliary colic and obstructive jaundice..

　　34.2% of patients in the chronic phase have no obvious symptoms. Common symptoms include fatigue, discomfort in the upper abdomen, abdominal pain, hidden pain in the liver area, and dizziness. Other symptoms include headaches, insomnia, decreased appetite, and diarrhea. In severe cases of repeated infection, liver cirrhosis and portal hypertension may occur, manifested by emaciation, anemia, edema, enlarged liver and spleen, ascites, and jaundice. In severely infected children, malnutrition and growth and development disorders may occur, and even dwarfism can be induced.

　　Some patients may experience sudden chills, high fever, enlarged liver with tenderness, mild jaundice, and in a few cases, spleen enlargement, with possible pulmonary infiltration. Acute symptoms disappear after several weeks and enter a chronic phase, characterized by fatigue, poor digestion, enlarged liver with tenderness, and dizziness. Headaches, insomnia, decreased appetite, and diarrhea are also common symptoms. In severe cases of repeated infection, liver cirrhosis and portal hypertension may occur, manifested by emaciation, anemia, edema, enlarged liver and spleen, ascites, and jaundice. In severely infected children, malnutrition and growth and development disorders may occur, and even dwarfism can be induced.

　　Clonorchis sinensis infection is caused by the consumption of raw or undercooked freshwater fish and shrimp containing metacercariae. To prevent Clonorchis sinensis infection, it is essential to focus on the oral transmission route and prevent the ingestion of viable metacercariae. It is important to conduct public education to make the public aware of the dangers and transmission routes of the disease, and to encourage them to avoid eating raw fish and undercooked meat or shrimp. Improving cooking methods and dietary habits, and ensuring that utensils for raw and cooked foods are not mixed, are also important. If cats and dogs in households have positive fecal tests, they should be treated. Do not feed cats and dogs with uncooked fish and shrimp to prevent infection. Strengthening fecal management and not allowing untreated feces to enter fish ponds are also important. Combining agricultural production activities, cleaning pond sludge, or using medication to kill snails can also play a role in controlling the disease.

　　Patients with cholangioclonorchiasis can undergo egg examination, immunological examination, and cholangiography, among other tests. The details are as follows:

　　1. The presence of eggs in feces can confirm Clonorchis sinensis infection, with an approximate detection rate of 50%. Common methods include direct smear, water wash precipitation, improved Katayama thick smear, and aldehyde ether methods. The latter two methods have higher detection rates. Eggs can be detected directly from the duodenal drainage fluid, with a detection rate close to 100%. Due to the inconvenience of the operation and the increased pain for patients, it is not suitable for routine use.

　　2, Enzyme-linked immunosorbent assay (ELISA) for diagnosing Clonorchis sinensis disease, with a serum positivity rate of 89.7% to 100%. This method is simple, rapid, requires a small amount of blood sample, has high sensitivity and specificity, is easy to judge the results, and is currently widely used. There are also many commonly used methods, with the positivity rate of intradermal tests being 92% to 95%, with about 5% false negatives, which can be used for preliminary screening, and the positivity rate of serum immunological indirect hemagglutination test (IHA) is 90%.

　　3, Blood count may show an increase in total white blood cell count and an increase in eosinophils; in severe infections, anemia may occur.

　　4, In patients with mild infection, liver function tests show minimal changes; in patients with severe infection, the main manifestations are decreased serum total protein and albumin, inversion of the albumin/globulin ratio, elevated ALP; normal or slightly elevated serum ALT.

　　5, In B-ultrasound examination, in cases of moderate to severe infection, it is common to see the intrahepatic bile ducts dilated, the liver enlarged, and the dilated small bile ducts distributed in a 'jungle' pattern. Around the dilated small bile ducts, there are small light spots without acoustic shadows or dot-like strong echoes along the portal vein branches, resembling 'stars' scattered.

　　6, Percutaneous liver biopsy cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP), with ERCP being more commonly used. The characteristics of bile duct造影 are: the dilated bile ducts are not thinning from thick to thin in a 'tree branch' pattern, but are suddenly cut off due to worm obstruction, appearing as 'bare branches' or with the tip appearing as 'cystic', and there are also thin filament-like or elliptical translucent areas inside the dilated bile ducts.

　　7, The typical CT changes caused by Clonorchis sinensis are that the intrahepatic bile ducts expand uniformly from the hilum towards the capsule, with similar diameters, which is obviously different from the bile duct expansion caused by general obstruction, which gradually narrows from the hilum to the periphery. The incidence of subcapsular bile duct ends expanding into cystic or rod-like shapes is also high, reaching 90.8% (148/163 cases), and CT can also show associated lesions simultaneously.

　　Clonorchis sinensis disease is caused by eating raw or undercooked freshwater fish or shrimp infected with Clonorchis sinensis metacercariae. Therefore, to prevent bile duct Clonorchis sinensis disease, it is best not to eat uncooked fish or shrimp.

　　The clinical manifestations of Clonorchis sinensis disease are evil excess and body deficiency, so the treatment should take the approach of invigorating the spleen and reinforcing the body, and expelling worms and soothing the liver, focusing on eliminating evil and treating both the root and branch, to play a positive role in treatment. The main prescription is as follows:

　　1, Feizhan Bing汤: Betel nut kernel 30g, Areca nut 15g, decocted in water for oral administration. Take one dose daily, with a course of 2 weeks.

　　2, Shugan Chuchong Decoction: Angelica sinensis 10g, Bupleurum 6g, Unripe orange peel 6g, Betel nut kernel 25g, Stemona root 15g, Areca nut 15g, Red peony root 12g, decocted in water for oral administration. Take one dose daily, with a course of 2 weeks.

　　3. The 方剂 of膈下逐瘀汤, with 9g of 当归, 12g of 桃仁, 9g of 红花, 6g of 枳壳, 9g of 赤芍, 3g of 甘草, 6g of 川芎, plus an appropriate amount of 五灵脂, 丹皮, 乌药, 延胡索, 香附, 槟榔. This formula is suitable for those with Qi stasis and blood stasis, with notable mass under the diaphragm. This decoction has a strong effect of relaxing the liver, promoting Qi, and relieving pain, and has a good therapeutic effect on chest and abdominal distension and pain caused by stasis under the diaphragm and stagnation of liver Qi.

　　4. The first formula for Clonorchis sinensis, with 12g of 党参 (or 太子参), 12g of 服苓, 10g of 白术, 12g of 扁豆, 15g of 山药, 10g of 郁金, 25g of 槟榔, 10g of 使君子, and 4.5g of 甘草.

　　5. The second formula for Clonorchis sinensis, with 10g of 郁金, 15g of 苦楝根皮, 25g of 榧子肉, and 25g of 槟榔. Method of use: First use the first formula, one dose per day, for 3 to 4 days, then switch to the second formula, one dose per day, for 5 to 7 days. If there are still eggshells in the patient's stool, the two formulas can be used alternately and repeated until the disease is cured.

　　According to the differences in clinical symptoms, appropriate additions and subtractions are made to the first formula, while the second formula remains unchanged. If there are symptoms such as chest stuffiness, nausea and vomiting, heavy limbs, and obvious dampness, add 半夏, 陈皮, 砂仁, 苍术 instead of 白术 to transform dampness and dryness; if there are obvious rib pain, belching, chest stuffiness, and liver qi flowing upwards, add 枳壳, 白芍, 柴胡 to relieve the liver; if there are dizziness, headache, insomnia, and liver Yin deficiency, add 女贞子, 早莲草, 白芍, 党参 to nourish the liver Yin; if there is ascites due to cirrhosis of the liver, add 丹参, 首乌, 菟丝子,

　　The herbs褚实子 and人参 are replaced with党参 to enhance the effect of invigorating the spleen, removing dampness, and softening the liver. For stronger constitution, take the first and second formulas first, then the first formula, with the same dose. For mild infection, 1 to 2 courses of treatment are generally sufficient to recover; for severe infection, generally 3 courses of treatment can cure it, and up to 4 courses of treatment can be taken to cure it.

　　6. 大柴胡汤, with 9g of 柴胡, 9g of 黄芩, 9g of 芍药, 9g of 半夏, 9g of 枳实, 6g of 大黄, 4 dates, and 12g of 生姜, is decocted in water for oral administration.

　　7. The formula of茵陈蒿汤, with 15g of茵陈蒿, 6g of栀子, and 6g of大黄, is decocted in water for oral administration. Patients can use the formula of 大柴胡汤 combined with 茵陈蒿汤, with additions and subtractions, suitable for those with liver and gallbladder damp-heat, aversion to cold, fever, pain in the ribs, yellowish eyes and bitter mouth, reddish tongue with yellow greasy fur, and wiry and rapid pulse, to treat this condition.