Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model.

BACKGROUND: European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection. METHODOLOGY/PRINCIPAL FINDINGS: In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver. CONCLUSIONS: A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis.

Ultrasonographic features of hepatobiliary pathology in opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma.

Infection with the liver fluke, Opisthorchis viverrini (Ov), is an important public health problem in northeast Thailand where people have a habit of eating raw or inadequately cooked fish. Opisthorchiasis is associated with a number of asymptomatic hepatobiliary abnormalities and cholangiocarcinoma (CCA) that can be observed conveniently by ultrasonography. Based on our accumulated data, characteristic features of ultrasonographic findings of hepatobiliary pathology in Ov infection are reviewed. Also, the ultrasonographic classification of periductal fibrosis in Ov infection of opisthorchiasis will be proposed herein.

Subtle to severe hepatobiliary morbidity in Opisthorchis viverrini endemic settings in southern Laos.

Evidence of severe hepatobiliary morbidity associated with Opisthorchis viverrini liver fluke infection including cholangiocarcinoma (CCA) is scarce in Laos although O. viverrini infection is highly prevalent. We assessed hepatobiliary morbidity using abdominal ultrasonography (US) in O. viverrini adult patients in Saravan province, Southern Laos. A random sample of 431 O. viverrini patients from 10 villages underwent abdominal US. Mild, moderate and markedly advanced periductal fibrosis was diagnosed in 7.0%, 66.5%, and 17.0% of patients, respectively. Normal liver parenchyma was seen in only 9.5% of patients. Presence of gall stones (13.2%), sludge (1.4%), gall wall thickening (1.2%), bile duct dilatation (1.6%), fatty liver (12.0%), kidney stones (8.6%) and cysts (7.9%) were diagnosed in considerable frequencies. In five patients (1.2%) hepatobiliary lesions suggesting CCA were diagnosed. Tumour markers, i.e. Interleukin-6, plasminogen activator inhibitor and carbohydrate antigen 19-9 were within normal range. The number of CCA suspected liver masses and hepatobiliary morbidity diagnosed among clinically asymptomatic adult patients in O. viverrini endemic area presents a major public health concern in Laos. However, definitive diagnosis of Opisthorchis-related severe sequelae including CCA is urgently needed to gauge the burden of this deadly disease in Laos.

Histological confirmation of periductal fibrosis from ultrasound diagnosis in cholangiocarcinoma patients.

Cholangiocarcinoma (CCA) has no specific clinical signs and symptoms and non-specific bio- and tumor-markers in the early disease stage. Usually patients present to tertiary care with advanced disease stage. In order to detect early cases of CCA that may present as a mass, dilatation of intrahepatic duct or combination, ultrasonography is accepted as a powerful imaging tool. A smaller mass or bile duct segmental dilatation requires further imaging for characterization, including computerized tomography (CT) or magnetic resonance imaging (MRI). We examined whether liver echo pattern was correlated with high risk for CCA in an endemic area of Opisthorchis viverrini (Ov). Ov infestation caused chronic inflammation of the biliary tree by periductal fibrosis (PDF), which may subsequently lead to CCA development. In our study, a World Health Organization classification of pattern of increased periportal echo (IPE) for schistosomiasis was applied. Two CCA patients gave consent for operation. Histopathological diagnosis showed both had cholangiocarcinoma with periductal fibrosis of the non-tumorous area of the liver. Ultrasonography was used to compare the non-tumorous area with parenchymal echo pattern and was shown to have an early CCA detection role and a surveillance role in an endemic area of Ov by detection of PDF.

Ultrasonography as a tool for monitoring the development and progression of cholangiocarcinoma in Opisthorchis viverrini/ dimethylnitrosamine-induced hamsters.

Cholangiocarcinoma (CCA) is the most common cancer in northeastern Thailand. At present, effective diagnosis of CCA either in humans or animals is not available. Monitoring the development and progression of CCA in animal models is essential for research and development of new promising chemotherapeutics. Ultrasonography has been widely used for screening of bile duct obstruction in CCA patients. In this study, we preliminarily investigated the applicability of ultrasonography to monitor the development and progression of CCA in Syrian golden hamsters (n=8) induced by Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN) administration. Ultrasonography and histopathological examination of hamsters was performed at week 0, 20, 24 and 28 of OV infection or at the start of water/Tween-80 administration to controls. The ultrasonographic images of liver parenchyma and gallbladders of OV/DMN-induced CCA hamsters showed sediments in gallbladder, thickening of gallbladder wall, and hypoechogenicity of liver parenchyma cells. The ultrasonographic images of liver tissues were found to correlate well with histopathological examination. Although ultrasonography does not directly detect the occurrence of CCA, it reflects the thickening of bile ducts and abnormality of liver tissues. It may be applied as a reliable tool for monitoring the development and progression of CCA in animal models in research and development of new promising chemotherapeutics for CCA.

Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand.

A cross sectional study on hepatobiliary abnormalities in opisthorchiasis was performed in 8936 males and females aged from 20 to 60 years from 90 villages of Khon Kaen province, Northeast Thailand. All were stool-examined for Opisthorchis viverrini infection by standard quantitative formalin/ethyl acetate concentration technique. Of these, 3359 participants with stool egg positive underwent ultrasonography of the upper abdomen. The hepatobiliary abnormalities detected by ultrasound are described here. This study found a significantly higher frequency of advanced periductal fibrosis in persons with chronic opisthorchiasis (23.6%), particularly in males. Risks of the fibrosis included intensity of infection, and age younger than 30 years. Height of left lobe of the liver, cross-section of the gallbladder dimensions post fatty meal, sludge, and, interestingly, intrahepatic duct stones were significantly associated with the advanced periductal fibrosis. Eleven suspected cholangiocarcinoma (CCA) cases were observed. This study emphasizes the current status of high O. viverrini infection rate and the existence of hepatobiliary abnormalities including suspected CCA in opisthorchiasis endemic areas of Thailand.

Ultrasound screening for Opisthorchis viverrini-associated cholangiocarcinomas: experience in an endemic area.

In Thailand, liver cancer is the most common malignancy in males and the third most common among females. In the Northeast region, cholangiocarcinoma (CHCA) is the prevalent type, with Opisthorchis viverrini (OV), an endemic liver fluke, being considered the cause. We evaluated the role of ultrasound (U/S) for cholangiocarcinoma screening as part of a larger cohort to characterize the linkage between liver fluke infestation and CHCA in Khon Kaen (Northeast Thailand). Most people (77%) had normal U/S findings while only 0.5% had suspected CHCA; thus, U/S should be used primarily for those with the highest risk, presenting symptoms and/or being OV positive.

Clinical manifestation of opisthorchiasis and treatment.

This paper presents an overview of recent progress in the clinical study of opisthorchiasis and treatment. Details of clinical manifestations of opisthorchiasis, hepatobiliary diseases and liver functions, community-based ultrasound study, treatment efficacy, and future study are discussed.

Opisthorchis viverrini infection in Thailand: studies on the morbidity of the infection and resolution following praziquantel treatment.

A community study on opisthorchiasis was conducted in Prachinburi Province in eastern Thailand during 1990-1992. The morbidity from opisthorchiasis in the community and reversibility of biliary pathology following treatment with praziquantel at a single dose of 40 mg/kg were assessed by longitudinal investigations of clinical, laboratory, and ultrasonographic changes. A total of 913 voluntary subjects infected with Opisthorchis viverrini were randomly selected for longitudinal study, and 579 subjects without liver fluke infection were recruited as controls. The majority of the study group suffered from mild and moderate infections that were associated with nonspecific gastrointestinal symptoms. Grade I and II ultrasonographic changes, which indicated chronic inflammation of the biliary tract and gallbladder, were detected in 32% of the infected individuals. Clinical symptoms and ultrasonographic changes were common in subjects 21-40 years of age and older. Satisfactory resolution of morbidity was observed during two years follow-up on days 0, 60, 180, 360, and 720, as shown by significant clinical improvement, normalization of laboratory parameters, and downgrading of ultrasonographic abnormalities. Portable ultrasonography has proved to be a reliable noninvasive technique in the evaluation of the morbidity due to opisthorchiasis in rural areas.

Opisthorchis viverrini infection in Thailand: symptoms and signs of infection--a population-based study.

A population-based study of the clinical, laboratory and ultrasonographic findings in patients suffering from mild or moderate opisthorchiasis in Prachinburi province, Thailand was conducted in 1990-1992. The effectiveness of treatment with praziquantel at 40 mg/kg body weight was evaluated. After treatment, a long-lasting, marked improvement in the well-being of the study group was observed. Symptoms common in opisthorchiasis infection decreased in intensity and the clinical response showed total or partial remission in 98% of all cases studied. Total and direct bilirubin concentrations decreased significantly and remained low up to the end of the follow-up period of 2 years, indicating a reduction in cholestasis. Also, white blood cell counts decreased initially, which can be interpreted as a reduction in inflammation intensity. No relationship was found between intensity of infection and age or clinical findings. Population-based treatment of opisthorchiasis appears to have had a significant impact on public health in north-east Thailand. However, it is also evident that drug therapy alone will not solve the opisthorchiasis problem, as indicated by the reinfection rate of almost 10% at the end of the study.

Trematode infections. Opisthorchiasis, clonorchiasis, fascioliasis, and paragonimiasis.

The parasitic diseases of the liver and lung are caused by trematodes or flukes--Opisthorchis viverrini, O. felineus, Fasciola hepatica, and Paragonimus westermani. Humans get infected by eating the second intermediate host of the fluke, for example, fish, crab, or water plant. The disease runs a chronic course. The diagnosis is made by the recover of eggs in stools or sputum, or by serodiagnosis. Praziquantel is the drug of choice except in falcioliaisis.

Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography.

Twenty-four locality-, age- and sex-matched groups of village residents with no light, moderate and heavy Opisthorchis viverrini infection were examined by ultrasonography. Highly significant differences were observed between the groups in the relative size of the left lobe of the liver and the fasting and post-meal size of the gall-bladder. In addition, indistinct gall-bladder wall, the presence of gall-bladder sludge and strongly enhanced portal vein radicle echoes were most frequently observed in the heavily infected group. Two suspected cases of cholangiocarcinoma were identified from the heavy group. The results highlight the importance of intensity of infection on the frequency and severity of fluke-associated hepatobiliary disease.

A high frequency of hepatobiliary disease and suspected cholangiocarcinoma associated with heavy Opisthorchis viverrini infection in a small community in north-east Thailand.

A group of 87 adults from a small village in north-east Thailand was chosen to undergo ultrasound investigation based on their intensity of infection with the liver fluke, Opisthorchis viverrini, or clinical status (history of jaundice, current hepatomegaly). From this group, 8 cases of suspected early cholangiocarcinoma were found, and the diagnostic features of 6 of the 8 were confirmed by computerized tomography scan and endoscopic retrograde cholangiopancreatography. In addition, several cases of mild gall-bladder disease, chronic cholecystitis, cholelithiasis and parenchymal liver disease were detected. A highly significant positive relationship between the intensity of liver fluke worm burden and the severity of biliary tract disease within individuals is reported. These results indicate that Opisthorchis is associated with moderate to severe hepatobiliary disease in a considerable proportion of infected individuals.

Computed tomography in opisthorchiasis.

Opisthorchiasis is a relatively common disease in the northeast of Thailand. Fifteen cases were studied by CT, revealing interesting findings: 1. Fourteen cases had abnormal liver CT. 2. Dilatation of intrahepatic biliary tree was very common, in various degrees. 3. Most patients had co-existing cholangiocarcinoma, some with peritoneal seeding and/or regional lymph node involvement. Metastases to pancreas, adrenal gland, spleen, lung and pleura are occasionally seen at initial diagnosis. CT findings are very suggestive of this disease. However, diagnosis depends on history, clinical and parasitological bases.

Opisthorchis viverrini infection: pathogenesis and clinical features.

The pathological changes are more or less related to the intensity and the duration of the infection, and are commonly seen in older patients with a large number of flukes. The pathogenesis is due to the mechanical irritation by the flukes and some toxic substances produced by them. Lesions are mainly confined to the biliary system. There is hyperplasia of the epithelial cells lining the bile ducts. In heavy and severe infections there are obstruction of the biliary tract, bile retention, extensive hyperplasia of the biliary system, with glandular proliferation of papillomatous and adenomatous type, cholangitis, periductal infiltration with eosinophils, round cells and fibrosis in the portal areas, necrosis and atrophy of hepatic cells. The bile ducts are dilated and in late cases saccular or cystic formations may develop into large cysts. The gallbladder may enlarge and contain white bile. The liver profile is generally normal. The majority of cases are symptomless. Clinical features vary from mild to severe. The symptoms and signs are vague gastro-intestinal symptoms, flatulence, anorexia, lassitude, weight loss, dull pain at the right hypochondrium, hot cutaneous sensation of the abdomen, and enlargement of the liver with some tenderness. In few cases the manifestations are severe. There is relapsing cholangitis, the patient is seriously ill and may succumb to septic shock. Cholangiocarcinoma, gallstones and obstructive jaundice are not unusual associations.

Roentgenographically controlled healing of gallbladder lesions in opisthorchiasis after praziquantel treatment.

In a study, gallbladder lesions due to Opisthorchis viverrini infection were controlled roentgenographically after treatment with praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinolin- 4-one, EMBAY 8440, Biltricide). The place of study was the Khon Kaen Hospital, Northeast Thailand. Included in the study were 20 patients with impairment of gallbladder function; 7 of them were males and 13 females. Their age ranged from 27 to 60 years (mean 47.4), eggs per gram (EPG) ranged from 800 to 30,000 (geometric mean 4321). The laboratory parameters were within normal limits. Praziquantel 3 X 25 mg/kg per kg body weight was given on Day 0 and all patients were parasitologically cured within 60 days. Oral cholecystography was performed to evaluate the function and size of the gallbladder and intravenous cholangiography for the common bile duct on Days 0, 14, 60, 120 and 180. The results were: (a) very large and severe dysfunction of gallbladder seen in three patients returned to normal in 60, 60 and 180 days; (b) moderate dysfunction was present in 13 patients, all but one returned to normal: 6 in 14 days, 1 in 21 days, 2 in 60 days, 1 in 120 days and 2 in 180 days. The only patient who showed no change had diabetes mellitus and moderate dysfunction of the gallbladder for one year prior to treatment; (c) mild dysfunction: all 4 patients were normal in 14 days. The common bile duct was enlarged in 3 patients (1.2, 1.3, 1.5 cm); no significant changes were seen.(ABSTRACT TRUNCATED AT 250 WORDS)