Clinical Overview of Clonorchis

Overview

Clonorchis is a liver fluke that can infect the liver, gallbladder, and bile duct.

• Clonorchis (also known as Chinese liver fluke disease), is part of the Opisthorchiidae family of liver flukes.
• People cannot get Clonorchis from another person, and they cannot get it from consuming untreated drinking water.
• Infections can last for several years (the lifespan of the parasite).

Cause

People can get Clonorchis infection when they eat raw or undercooked freshwater fish that contains the larvae. Freshwater snails can eat the eggs of Clonorchis and become infected, releasing microscopic larvae that then enter freshwater fish. When humans eat raw or undercooked fish with the larvae, these larvae grow into adult flukes. These flukes then live inside the human bile duct system of the liver. The life cycle takes three months to complete in humans. People who are infected can pass eggs in their stool or may cough them up.

At-risk populations

Clonorchis infections occur most often in people living in some places in Asia, especially Korea, China, Taiwan, Japan, Asian Russia, Thailand, Cambodia, Laos, Northern Vietnam, and the Philippines.

Additional people who are at risk include:

• Travelers to parts of Asia where the parasite occurs who consume raw or undercooked fish
• Asian immigrants from areas where the parasite occurs

Risk factors

Eating raw or undercooked freshwater fish from countries where infection is common is the key risk factor for Clonorchis infection. Lightly salted, smoked, or pickled fish can also contain infectious parasites.

Signs and symptoms

Most people infected with Clonorchis do not have symptoms. When people have symptoms, they are generally gastrointestinal (GI) and can range from mild to severe. Symptoms may be the result of inflammation of the liver or gallbladder or blockage of the bile duct caused by the fluke.

Symptoms and signs can include one or more of the following, depending on the number of flukes and length of infection:

• Indigestion
• Nausea
• Abdominal pain
• Enlarged liver
• Diarrhea
• Constipation
• Fever
• Jaundice

If left untreated, Clonorchis infection can last for several years (the lifespan of the parasite). A person may have multiple liver fluke infections if they live in an area where liver flukes exist and eat raw or undercooked freshwater fish. Children with heavy infections and/or repeated infections are at risk for malnutrition.

Clonorchis is associated with cholangiocarcinoma (CCA), a rare cancer of the biliary duct system, which comprises of the gallbladder and bile ducts. Only a small percentage of people infected with Clonorchis develop CCA. There are multiple non-parasitic risk factors for CCA, and liver fluke infections, specifically Clonorchis and Opisthorchis (but not Fasciola), are very rarely associated with cases of CCA in the US. Approximately 90% of patients diagnosed with CCA in western countries do not have a recognized risk factor.

Longstanding inflammation due to Clonorchis infection is associated with CCA. More common risk factors for CCA in the US include:

• Hepatitis B
• Hepatitis C
• Alcoholic liver disease

However, most patients in Western countries who develop CCA do not have Clonorchis infection.

Prevention

People can avoid Clonorchis infection by not eating raw or undercooked freshwater fish from countries where the parasite occurs. Lightly salted, smoked, or pickled fish can also contain infectious parasites.

The FDA recommends the following for fish preparation or storage to kill parasites:

Cooking

• Cook fish to an appropriate level (to an internal temperature of at least 145° F [~63° C]).

Freezing

• At -4°F (-20°C) or below for at least 7 days (total time); or
• At -31°F (-35°C) or below until solid, and storing at -31°F (-35°C) or below for a least 15 hours; or
• At -31°F (-35°C) or below until solid and storing at -4°F (-20°C) or below for at least 24 hours.

Diagnosis

Ova and parasite (O&P) stool examinations for liver fluke eggs can diagnose Clonorchis infection.

Stool specimen

• Microscopy can identify Clonorchis eggs in stool specimens.
• Healthcare providers can collect three stool samples, each on a different day, for O&P examination to identify the eggs due to intermittent shedding.
• Note: Stool examination is unlikely to be useful for people with remote exposure to Clonorchis parasites (e.g., three decades ago or longer, beyond the lifespan of the fluke).

Ultrasound, CT, or MRI

• At times, ultrasound, CT, or MRI can detect dilated bile ducts containing the fluke and help make the diagnosis.

Blood test

• A serologic test for detecting Clonorchis is available in the US at Kephera Diagnostics in Massachusetts.
• Serology is less useful than O&P examination for diagnosis and patient management because it cannot distinguish between current and past infection.
• In the absence of detection of liver flukes, there is no test available that can determine if liver fluke infection is the underlying cause of cholangiocarcinoma or other hepatobiliary conditions. Routine screening is not recommended for asymptomatic individuals with a history of travel to endemic countries with liver fluke infection.

Treatment and recovery

Praziquantel is the treatment of choice for Clonorchis infections. Albendazole is an alternative drug option. Both oral praziquantel and oral albendazole are available for human use in the United States.

*Not FDA-approved for this indication

This information is provided as an informational resource for licensed healthcare providers as guidance only. It is not intended as a substitute for professional judgment.

Care Precautions

Praziquantel

Treatment in Pregnancy

Praziquantel is a pregnancy category B drug. There are no adequate and well-controlled studies in pregnant women. However, the available evidence suggests no difference in adverse birth outcomes in the children of women who were accidentally treated with praziquantel during mass drug administration (MDA) campaigns compared with those who were not. In MDA campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO encourages the use of praziquantel in any stage of pregnancy. For individual patients in clinical settings, healthcare providers should consider the risk of treatment in infected pregnant women with the risk of disease progression in the absence of treatment.

Pregnancy Category B: Either animal-reproduction studies have not demonstrated a fetal risk plus there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Treatment During Lactation

Praziquantel is excreted in low concentrations in breast milk. According to WHO guidelines for MDA campaigns, the use of praziquantel during lactation is encouraged. For individual patients in clinical settings, healthcare providers should consider the risk of treatment in infected breastfeeding women with the risk of disease progression in the absence of treatment.

Treatment in Pediatric Patients

The safety of praziquantel in children aged less than 4 years has not been established. WHO now recommends treating children at least 2 years of age with praziquantel during MDA campaigns for schistosomiasis control, citing evidence that praziquantel is safe in this age group. For individual patients in clinical settings, healthcare providers should consider the risk of treatment in children younger than 4 years old with the risk of disease progression in the absence of treatment.

Albendazole

Treatment in Pregnancy

Albendazole is a pregnancy category C drug. There are limited data on the use of albendazole in pregnant women. The available evidence suggests no difference in congenital abnormalities in the children of women accidentally treated with albendazole during mass drug administration (MDA) campaigns compared with those who were not. In MDA campaigns for which the World Health Organization (WHO) has determined that the benefits of treatment outweigh the risks, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy in these campaigns. However, healthcare providers should balance the risks of treatment for the fetus with the risks of disease progression in the woman in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) plus there are no controlled studies in women, or studies in women and animals are not available. Prescribe albendazole only if the potential benefits to the woman justify the potential risks to the fetus.

Treatment during lactation

Albendazole is minimally excreted in human milk. WHO has concluded that a single oral dose of albendazole can be given to lactating women.

Treatment in pediatric patients

The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that it is safe. According to WHO guidelines for MDA campaigns, children as young as one year of age (able to safely swallow tablets) can take albendazole. These campaigns have treated many children under six years old with albendazole, albeit at a reduced dose.

Similar diseases

Clonorchis eggs are very similar to those of Opisthorchis (another liver fluke) eggs but can be distinguished by microscopic features.