Case #18011

A man from Mexico with a liver lesion

History of Present Illness

A man from Mexico in his forties with known alcoholic cirrhosis and chronic anemia requiring multiple blood transfusions was admitted from outpatient hepatology clinic with worsening anemia (hemoglobin 3.6 g/dL), fatigue and increased dyspnea on exertion over the past 5 months. He initially noticed symptoms of fatigue and myalgias 10 months ago, which prompted presentation to outside clinics where blood tests revealed hemoglobin less than 5.5 g/dL. The patient denied abdominal pain, melena, hematochezia, fever, chills, or jaundice.

The two previous hospitalizations involved blood transfusions and workup with upper endoscopy and colonoscopy, both of which revealed healthy tissue. However, a magnetic resonance cholangiopancreatography (MRCP) showed an ill-defined mass at the porta hepatis extending into the right hepatic lobe and coursing along the common bile duct with intrahepatic biliary ductal dilatation. Abdominal ultrasound showed cirrhotic liver morphology and intra- and extra-hepatic biliary dilatation with nonvascular echogenic material in the right and common bile ducts concerning for cholangiocarcinoma. Additionally, echogenic material within the gallbladder neck suggested malignancy or sludge. These concerning findings prompted recommendation for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP), which was not performed until 5 months later as the patient was lost to follow-up until present hospitalization.

Past Medical History
He has a history of Child A cirrhosis secondary to alcohol dependence and chronic microcytic anemia. Patient had no known drug allergies.
Medications
Although ferrous sulfate had been previously prescribed for chronic microcytic anemia, he reported never taking this medication. He denied taking any other medications or supplements.
Epidemiological History
One year prior, he immigrated to the United States from Mexico. He reported a single hospitalization in Mexico where he was diagnosed with cirrhosis and underwent treatment with multiple paracentesis procedures. In Mexico, he worked as a farmer harvesting corn and beans; he noted that bulls, donkeys, sheep and horses roamed nearby. He has not visited Mexico since leaving and denies other recent travel. His diet is varied and includes fresh vegetables, including raw watercress. He denies consuming raw fish, liver or organ meats, or unpasteurized cheeses. He resides in California, USA with his family. He reports occasional cigar use, previous heavy alcohol use until 3 years prior, and denies injection drug use.
Physical Examination
Physical examination revealed a temperature of 36.6°C (97.9°F), a pulse of 71 beats/min, blood pressure of 144/51 mmHg, and respirations of 19 breaths per minute with oxygen saturation 100% on room air. He is an overweight middle-aged man. Scleral icterus and jaundice were noted, as well as mildly distended but non-tender abdomen. A holosystolic murmur was auscultated over the right upper sternal border. The rest of the physical exam was normal.
Studies

Blood tests revealed the following: Hemoglobin 3.6 g/dL (reference range 13.5 to 16.5 g/dL), hematocrit 14.2% (reference range 40%-49%), WBC 5,200 mm3 (reference range 4,500-10,000 mm3), platelets 241,000 mm3 (reference range 160,000-360,000 mm3) and eosinophils 15.7% (reference range 0%-7%) with absolute eosinophil count 800 mm3 (reference range 0-400 mm3). Notably, absolute eosinophil count was 500 to 1300 mm3 in the 8 months preceding current hospitalization. Alkaline phosphatase was elevated at 164 U/L (reference range 40-129 U/L) with normal aspartate aminotransferase (AST, 20U/L) and alanine aminotransferase (ALT, 16 U/L). Total bilirubin was 0.4mg/dL (reference range <1 mg/dL). Schistosoma antibody (IgG) was not detected. Blood cultures obtained were negative for growth.

Magnetic resonance cholangiopancreatography (MRCP) showed an ill-defined mass at the porta hepatis extending into the right hepatic lobe and coursing along the common bile duct with intrahepatic biliary ductal dilatation (Fig. 1).

Abdominal ultrasound showed cirrhotic liver morphology and intra- and extrahepatic biliary dilatation with nonvascular echogenic material in the right and common bile ducts concerning for cholangiocarcinoma. Additionally, there was echogenic material within the gallbladder neck suggestive of malignancy or sludge.

What is the diagnosis?





 

Diagnostic Procedure(s) and Result(s)

The endoscopic ultrasound evaluation was notable for a markedly dilated common bile duct with heterogenous material throughout the duct and gallbladder without obvious masses. Initial cholangiogram demonstrated filling defect throughout the extrahepatic duct with dilation to 1cm. Endoscopic sphincterotomy was performed and the common bile duct was swept of what was described as purple debris (Fig. 2). On closer inspection, the lesions were mobile and most compatible with a flat worm (Fig. 3). Several short videos were taken (Video 1) and several worms (at least 5) were retrieved with a mesh net and sent to microbiology for organism identification (Fig. 4). The retrieved worms were identified as Fasciola hepatica, with the identification confirmed by the CDC. Stool analysis showed multiple F. hepatica ova present (Fig. 5). Prior to treatment, the patient’s serum was sent to the CDC for the immunoblot assay that detects antibody to FhSAP2, a recombinant antigen derived from Fasciola hepatica and the antibody was identified in the patient’s serum.


Video 1. Video of single trematode within biliary tract at ERCP. (Courtesy of LAC+USC GI Endoscopy Lab)

Treatment and Followup
Treatment was initiated with triclabendazole, a benzimidazole derivative with demonstrated activity against mature and immature trematodes that is available under investigational protocol from the CDC as it is not FDA approved in the United States. Given the high quantity of worms removed and severe infection with chronic anemia and jaundice, the decision was made to treat with two doses of triclabendazole. The medication was administered orally and post-prandially after a fatty meal to increase absorption and concurrently with antispasmodics (eg. hyoscyamine) to reduce pain and minimize risk of jaundice. Clinical follow-up with Infectious Disease and Gastroenterology in the two months after treatment revealed improvement in anemia and eosinophilia. Patient has since been lost to follow-up.
Discussion

Fascioliasis is a zoonotic infection caused by the foodborne trematode, Fasciola hepatica, with global prevalence, especially endemic in sheep and cattle-raising areas of South America, the Caribbean, northern Africa and western Europe [1]. Adult flukes are flat, brown, leaf shaped worms, measuring up to 3 cm in length. Sheep liver fluke infestation results from ingestion of larvae encysted on uncooked watercress or other fresh aquatic vegetation like water caltrops, water lettuces, mint or parsley, typically found near infected animals, or through consumption of metacercariae-contaminated water [2]. These cercariae can remain viable on vegetation for months.

The infective metacercariae excyst after being swallowed. The juveniles penetrate the intestinal wall, migrate through the peritoneal cavity and liver capsule, and feed on liver parenchyma before entering the biliary tract, where they mature and release 20,000 to 24,000 eggs per fluke per day [1,3]. The acute hepatic migratory phase of the life cycle occurs within 6 to 12 weeks of ingestion of metacercariae. After 3 to 4 months, the worms enter the biliary tract where they mature and remain as adults. Adult flukes can live for as long as 10 years in humans, who are accidental final hosts [1].

F. hepatica in the acute hepatic migratory phase can cause right upper quadrant pain, intermittent high fever, weight loss, urticaria, jaundice, anemia and eosinophilia. Interestingly, this patient had high absolute eosinophils, which is uncommon during the biliary chronic phase of the F. hepatica infection. In the chronic phase, F. hepatica infection may be subclinical or may cause progressive inflammation with bile duct dilatation and fibrosis related to mechanical obstruction of the ducts and the activity of proline, which the fluke excretes to facilitate movement through the narrow ducts [2]. Anemia may result from blood loss through bile duct lesions. The origin of this patient’s anemia likely resulted from chronic Fasciola infestation. Case reports suggest mortality from hematobilia more commonly in children [1].

The diagnosis of fascioliasis is often difficult due to non-specific clinical symptoms and low suspicion due to its rarity in the West. Computerized tomographic scan and ultrasonographic findings may suggest biliary pathology that prompts further endoscopic evaluation, as in this patient who underwent MRCP showing a mass-like lesion suggestive of cholangiocarcinoma. Definitive diagnosis of fascioliasis can be made by visual detection of living flukes by laparotomy or endoscopic imaging and observation of eggs in the stool. The presence of F. hepatica ova in this patient’s stool confirmed chronic infection, as only mature adult flukes will release eggs. Fasciola specific serological response occurs within 2 to 4 weeks of infection and is helpful to detect active infection [2]. Serology should revert to negative within one year of successful treatment.

A single dose of triclabendazole, which is a well-tolerated benzimidazole used in veterinary practice, is the regimen of choice against fascioliasis. Triclabendazole is highly effective against mature and immature flukes with high cure rates (reportedly 78% to 99%) [1, 4]. Treatment should be repeated with a second dose if radiologic findings or eosinophilia fail to resolve or serologic titers do not decrease. This patient was treated with two doses of triclanbendazole given severity of anemia, eosinophilia and jaundice associated with high worm burden. Concurrent administration of the anti-spasmodic agent hyocyamine appeared to mitigate abdominal pain associated with fasciolicide [4].

Prevention of fascioliasis involves strategic treatment or immunization of herbivorous animals that maintain the life cycle as well as health education to discourage the consumption of raw watercress and other edible water plants [2]. Our patient reported enjoying raw watercress salads weekly for many years, even prior to immigration from Mexico to the United States one year ago.

Final Diagnosis
Fascioliasis
References
  1. Maguire, James H. “Trematodes (Schistosomes and Liver, Intestinal and Lung Flukes)”. Mandell, Douglass, and Bennett’s Principles and Practice of Infectious Diseases, 8th Ed. Philadelphia: Elsevier, 2015, pp 3216-3224.
  2. Sithithawaorn, Paiboon, et al. “Food-borne Trematodes”. Pp 726-731. Manson’s Tropical Diseases, 23rd Ed. Saunders Ltd, 2014, pp 726- 731.
  3. Cwiklinski, K., et al. A prospective view of animal and human Fascioliasis. Parasite Immunology (2016); 38, 558-568. DOI: 10.1111/pim.12343 PMID:27314903 (PubMed abstract)
  4. Laburte, Ch. Egaten: Summary of Product Characteristics. Novartis Pharma AG, Basel, Switzerland (2000).
  5. Lu, Ziao-Ting, et al. Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods. Infectious Diseases of Poverty (2018); 7:28. DOI: 10.1186/s40249-018-0414-7 PMID:29628017 (PubMed abstract)
  6. Lefryekh, Rachid, et al. Hepatic fascioliasis presenting with bile duct obstruction: a case report. Pan African Medical Journal (2017); 28:44. DOI: 10.11604/pamj.2017.28.44.11532. PMID:29158867 (PubMed abstract)
  7. Niknam, Ramin, et al. Three Living Fasciola Hepatica in the Biliary Tract of a Woman. Iran Journal of Medical Science (Sept 2015); 40:5. PMID:28379355 (PubMed abstract)
Notes

ID week Fellows' Day 2018 - oral presentation

This case was contributed by:

Erin N. Dizon, MD (1), Paul Holtom, MD, FIDSA, FSHEA (1) and Susan M. Butler-Wu, PhD, D(ABBM) (2)

(1) Los Angeles County + University of Southern California Medical Center, Los Angeles, CA

(2) Clinical Microbiology Laboratory, LAC-USC Medical Center, Los Angeles, CA

The case was originally presented at ID Week 2018, a joint effort of Infectious Diseases Society of America (IDSA), HIV Medical Association, Pediatric Infectious Diseases Society (PIDS), and the Society for Healthcare Epidemiology of America (SHEA), during an interactive session on Fellows' Day. Copyright Infectious Disease Society of America (IDSA), 2018. Used with permission.

Last reviewed: 9 March 2019

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