A 43-year-old female, whose height was 160 cm and weight 46 kg [body mass index (BMI) 18.0], was admitted due to 2 months of repeated fever and space-occupying lesions in the liver on May 15, 2020 (day-1). The highest body temperature appeared at night but returned to normal in the morning, with dry cough, shortness of breath, and dull pain in the liver area. The physical examination of the whole body showed no obvious positive signs, there were no abdominal tenderness and percussion pain, and no enlarged superficial lymph nodes were palpated. So, the patient still could live and work properly. She lived in Chongqing city, whose economic situation is medium as a furniture sales staff. She visited Guangzhou province 6 months ago on business for 2 days. She denied any contact with livestock and eating wild vegetables, raw fish, shrimp, and so on, but drank tap water every day. The local hospital prescribed empirical antimicrobial therapy with azithromycin and Chinese herbal medicines; however, the treatment failed to relieve the symptoms of the patient. Thus, the patient was transferred to our hospital for further evaluation. An outline of the episodes is described in Figure 1. Chest CT scan showed no infection in the lungs, while mass-like shadows in the liver were observed on the abdominal CT scan. Routine blood parameters revealed elevated white blood cell and eosinophil count (Figure 2).
Enhanced MRI of the upper abdomen showed the increased liver volume, uneven liver parenchyma signal, liver interstitial edema, and accumulated fluid in the abdominal cavity on hospital day 2 (Figure 3A). Laboratory tests showed elevated IgE (333 ng/mL), white blood cell, and eosinophil count on hospital day 5. Microbial tests, including blood cultures, stool examination, and stool precipitation, did not detect any pathogens. Eggs were not detected by direct fecal smear and fecal washing precipitation. Due to excessive pharyngeal reflex during gastroduodenal tube placement, two attempts failed to obtain the bile of the patient. The diagnosis of tuberculosis was excluded for the negative results of the chest CT scan, tuberculin skin test, tuberculosis IgG and IgM antibody screening, and T-Spot examination. Meanwhile, ovarian tumors, liver tumors, gastrointestinal tumors, and hematological tumors were also excluded temporarily as the negative results of abdominal enhanced CT and tumor marker detection such as AFP, CA-50, CEA, TAP, CA-125, CA-199, CA-242, and CA-724 and so on. The serum parasite IgG antibody, including schistosome, paragonimiasis, cysticercosis, trichinella spiralis, liver fluke, sparganosis, and hydatid IgG antibody detected by ELISA were negative on hospital day 12. Piperacillin-sulbactam was used as an antibacterial treatment for 10 days from hospital days 4-13.
However, the body temperature of the patient fluctuated several times, and the eosinophil count was not significantly reduced (Figure 2). So, an enhanced CT of the lower abdomen was performed on hospital day 13, which showed multiple shadows of abnormal density in the liver and a small amount of effusion, suggesting the possibility of infectious and neoplastic lesions (Figure 3B). Because of the high fever, biapenem was adjusted to be used to cover drug-resistant bacteria for more than 2 weeks from hospital day-14 to day-32.
To further confirm the diagnosis, an ultrasound-guided percutaneous liver biopsy was conducted on hospital day-14. The hepatic histopathology reported mild inflammation in the portal area and eosinophil infiltration in the inflammatory necrotic area, with no evidence of malignancy, liver abscess, and parasitic infection on hospital day 20 (Figure 1).
As treatment with antibiotics was ineffective (long-term fever, significantly elevated eosinophils count, intrahepatic lesions), the enhanced MRI of the upper abdominal was re-examined on hospital day 33, which indicated no absorption of intrahepatic lesions (Figure 3C). Meanwhile, combined with Chongqing epidemiological studies of Clonorchis sinensis, parasite infection was suspected and praziquantel was used as treatment. The body temperature decreased, and the patient was discharged on day 36.
During the period of hospital days 33 and 67, the patient still had repeated fever with a maximum temperature of 39 C (Figure 2). An enhanced MRI of the upper abdominal showed that the liver shadow had less absorption (Figure 3D). So, albendazole was adjusted as the treatment on the follow-up day. Albendazole was orally taken 0.8 g once a day for half a month. As the body temperature of the patient decreased, the dose of albendazole was decreased to 0.6 g for half a month after drug withdraw. On the follow-up day, the dose of albendazole was not adjusted and the patient was prescribed to take albendazole according to taking half a month and stopping for half a month. Firstly, the peak temperature of the body decreased significantly. Secondly, the eosinophil count decreased and ultimately returned to normal. However, there was still a high fever up to 40 C (Figure 2), occasionally. Meanwhile, the enhanced MRI of the upper abdominal reexamined on follow-up day 137 showed that there was no significant absorption of the lesions compared with the previous (Figure 3E). So far, after a total of 106 days of empirical anti-parasitic treatment, the body temperature and eosinophil count decreased significantly, but the imaging manifestations did not improve significantly.
To identify the pathogen, liver tissue collected on hospital day 14 and peripheral blood on follow-up day 137 were sent for mNGS with the written consent of the patient. The total reads of the liver tissue and blood were 6.93 and 30,379 Mb, respectively. Meanwhile, the reads mapped to microbes in the liver tissue and blood were 934,425, and 29,009. The number of species-specific reads aligning to the Fasciola hepatica genome in the liver biopsy and blood was 3 and 51, respectively (Figure 4). Finally, the disease was diagnosed with fascioliasis hepatica with triclabendazole as the first-line drug. However, for the sake of the unavailability of triclabendazole under the epidemic of COVID-19 in China and other countries, and the partial effectiveness of albendazole on the fascioliasis hepatica which significantly decreased the body temperature and eosinophil count of the patient, albendazole was used with a prolonged treatment time following the previous way.
Eventually, after receiving treatment of albendazole for more than 7 months, the body temperature and eosinophil count of the patient normalized with no obvious clinical manifestations. So, albendazole was discontinued on day-300. After more than 3 months after drug withdrawal on follow-up day 148, the enhanced MRI of the upper abdominal showed that the intrahepatic low-density shadow was smaller (Figure 3F), and the blood mNGS was negative (Table 1), suggesting the albendazole treatment was effective.