Alveolar Echinococcosis Mimicking Perihilar Cholangiocarcinoma Leading to Liver Transplant: A Case Report

Introduction

Alveolar echinococcosis (AE) is a chronic infectious disease caused by the metacestode stage of Echinococcus multilocularis, contracted by the ingestion of infective eggs [1]. AE is endemic to the Northern Hemisphere, particularly in regions such as central and eastern Europe, Russia, China, and northern Japan [2,3]. Annual incidence ranges from 0.007 per 100 000 population in Canada to 2.62 per 100 000 in Kyrgyzstan. In Croatia, the annual incidence is 0.03 per 100 000, resulting in 1 to 2 new cases per year [4]. The liver is the primarily affected organ (98% of cases), and the disease clinically resembles a slow-growing tumor. AE can spread beyond the liver parenchyma through direct invasion or metastasis formation [2,5]. It is out of paramount importance to differentiate AE from primary and secondary liver neoplasms, due to the diagnostic and therapeutic implications [6]. Extrahepatic manifestations, particularly perihilar involvement, are rare and uncommon first AE presentations and present a unique diagnostic challenge. Herein, we present a case of a patient in whom AE clinically resembled perihilar cholangiocellular carcinoma (Klatskin tumor) and who underwent subsequent treatment with liver transplantation, underscoring the importance of considering AE early in differential diagnosis of suspected liver malignancy.

Case Report

In October 2022, a 32-year-old male patient with an unremarkable past medical history was admitted to our Gastroenterology Department for evaluation of a liver lesion detected during routine laboratory testing, which indicated dominant cholestasis (aspartate transaminase 93 U/L; alanine transaminase 178 U/L; gamma-glutamyl transferase 671 U/L; alkaline phosphatase 341 U/L), with normal bilirubin levels. The patient underwent magnetic resonance cholangiopancreatography (MRCP), which identified an irregular mass measuring 26 mm at the bile duct confluence and dilated intrahepatic biliary ducts for both lobes, along with enlarged lymph nodes in the porta hepatis, which are radiomorphological characteristics indicative of a Klatskin tumor (Bismouth-Corlette type IV; Figure 1).

At admission, the patient was fully alert, oriented, and in good general health. Abdominal examination revealed a soft, painless abdomen at the level of the chest, with audible peristalsis and without palpable hepatosplenomegaly. Laboratory test results continued to show cholestatic enzyme elevation, with normal bilirubin levels. Prothrombin time and serum albumin levels were within the reference ranges. The screening for hepatitis, storage diseases, and autoimmune markers was negative. The cancer antigen 19-9 level was within the reference range, at 23 U/mL.

The liver stiffness measurement, using transient elastography, showed a slightly elevated value of 12.4 kPa. A subsequent multislice computed tomography scan (MSCT) of the thorax and abdomen confirmed the MRCP findings. Endoscopic ultrasound with fine needle aspiration of the hilar mass and an enlarged lymph node was performed, but cytological examination did not reveal malignant cells. Subsequently, diagnostic endoscopic retrograde cholangiopancreatography (ERCP) was performed, which was complicated by common bile duct perforation and biliary leakage, leading to emergency surgical duct repair. During this procedure, an enlarged lymph node alongside the common bile duct, which was suspected macroscopically for carcinoma metastasis, was removed. However, pathohistological examination revealed only reactive inflammatory changes, and cytobrush samples collected during ERCP were negative for malignancy. After patient recovery, the hilar mass was biopsied again under MSCT guidance, but remained undiagnostic. An IgG-4 panel returned negative as well. The patient was discharged, and follow-up magnetic resonance imaging (performed 2 months after the initial one) revealed no signs of disease progression. A positron emission tomography (PET) scan with fluorodeoxyglucose was also performed, but it was inconclusive for malignancy. Due to the overt icterus (bilirubin level 123 μmol/L) and persistence of the diagnostic uncertainty, the patient was readmitted to our Hepatology and Transplantation Center for further evaluation. An ultrasound-guided percutaneous biopsy of the lesion in the liver hilum was performed, and the final pathology finding was surprisingly indicative of AE. Treatment with albendazole at a dose of 15 mg/kg/day was initiated in January 2024, due to the inoperability of the parasitic mass, with the intention of slowing disease progression.

Despite albendazole therapy, the disease course progressed, with the patient experiencing 2 episodes of cholangitis within a month, accompanied by worsening jaundice (maximum bilirubin level 173 μmol/L). A repeated PET scan did not demonstrate extrahepatic disease spread. Given the progressive course and repeated cholangitis episodes, a multidisciplinary team recommended liver transplantation. Extensive pre-transplant evaluation revealed no contraindications, and on June 15, 2024 (5 months after albendazole therapy initiation and 20 months after urgent operative procedure), the patient underwent orthotopic liver transplantation with hepaticojejunal anastomosis, successfully achieving complete removal of the parasitic tissue. The explanted liver contained a perihilar, macroscopically whitish, partially calcified mass measuring 45 mm. Microscopically, the mass consisted of parasitic vesicles composed of chitinous membranes surrounded by chronic inflammatory infiltrate, consisting of epithelioid histiocytes, fibroblasts, giant cells, and numerous mononuclear cells. The parasitic vesicles infiltrated veins and bile ducts in the liver hilum. Only a few bridging fibrosis tracts were detected in the explanted liver (fibrosis stage according to the Ishak scoring system was 2/6).

The standard immunosuppressive protocol following liver transplantation included corticosteroids, tacrolimus, and mycophenolate mofetil combination, with continued albendazole therapy. At the time of this report, the patient continued to be regularly monitored on an outpatient basis. The graft function has been stable, with no signs of residual disease or albendazole induced hepatotoxicity.

Discussion

The clinical course of AE is chronic, with a long incubation period (5–15 years) [7,8]. Common symptoms and signs include abdominal pain and cholestatic jaundice, with both symptoms present in one-third of patients. However, in about one-third of patients, AE is oligosymptomatic and found incidentally during routine evaluation for fatigue, weight loss, or hepatomegaly. Diagnosis is established through a combination of clinical examination, epidemiological data, radiomorphological examination, and serological testing. Definitive diagnosis is established histopathologically or by demonstrating the parasite’s nucleic acids in tissue samples. However, clinical suspicion remains the most important factor in achieving early diagnosis of AE, particularly in countries with a low annual incidence, such as Croatia. Abdominal ultrasound is typically the first morphological method used, revealing a pseudotumor with irregular borders, consisting of hypo- and hyperechoic areas and calcifications, seen in 70% of cases. MSCT and magnetic resonance imaging provide further morphological lesion characterization, while MRCP defines the lesion’s relationship to the biliary tree more precisely. PET-CT (performed 3 h after radiopharmaceutical administration) indicates periparasitic inflammatory activity and is valuable in the diagnosis and monitoring of patients [3,9,10]. Despite the numerous options in radiological diagnostics, distinguishing AE from primary and secondary malignant lesions remains challenging, as exemplified by our case, in which AE mimicked a Klatskin tumor.

Similar to our case, authors from Turkey and China documented 2 patients with AE radiologically and clinically resembling Klatskin tumor, with definitive diagnosis established upon true-cut needle biopsy and surgical specimen examination, respectively [6,11]. Authors from the Czech Republic presented a case of a 38-year-old patient with 2 large tumor formations in the right hepatic lobe and 2 nodular lesions in the lung parenchyma, suggesting advanced cholangiocellular carcinoma; however, AE was histopathologically confirmed in the postoperative tissue samples [2]. Similarly, Swiss authors in 2017 reported a 62-year-old patient who presented with clinical features of advanced malignant disease, and AE diagnosis was established posthumously after the patient died of biliary sepsis [12].

AE is staged using the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) parasite mass-neighboring organ involvement-metastasis (PNM) classification, which mirrors the tumor-node-metastasis (TNM) system for malignancies, standardizing disease extension and guiding therapy. According to this classification, AE in our patient could be classified as P3N0M0 and clinical stage IIIa. Treatment of AE should be planned within multidisciplinary teams consisting of abdominal surgeons, gastroenterologists, interventional radiologists, and infectious disease specialists. Radical resection is the primary treatment when feasible, aiming for a 2-cm margin of healthy tissue. Resectability varies from 15% to 87%, depending on disease stage, patient condition, and surgeon expertise. Long-term chemotherapy with benzimidazoles is required after resection, for inoperable cases and after liver transplantation. Advanced stages of the disease, mainly IIIa to IV, which exceed resectability limits and are accompanied by portal hypertension, Budd-Chiari syndrome, or recurrent cholangitis, can necessitate liver transplantation as a salvage option [1,3]. Our patient underwent liver transplantation, due to the unfavorable perihilar location of a parasitic mass, which exceeded the limits of surgical resection as a consequence of late diagnosis and disease progression. This was accompanied by recurrent cholangitis, despite ongoing albendazole therapy. Liver transplantation was considered to be in the patient’s best interest, as it enabled complete removal of the parasitic mass, with the intention of achieving a cure. A previous urgent biliary operation did not influence the treatment course or the decision to proceed with liver transplantation, as the perforation involved the distal portion of the common bile duct was promptly recognized and successfully managed, resulting in no additional biliary complications. Authors from Turkey presented 27 patients with liver transplantation due to AE, with a main indication of hilar invasion (14/27), similar to in our patient. During follow-up (16.1±14.1 months), the survival rate was 77.8% [1].

To the best of our knowledge, Breson-Hadni et al [5] reported the largest overview of patients with liver transplantation due to AE. A retrospective analysis was conducted on 47 patients undergoing transplantation between 1985 and 2002 (25 males and 22 females, aged between 16 and 67 years). The most common indications for liver transplantation were recurrent episodes of cholangitis (57% of patients) and secondary biliary cirrhosis (30% of patients). The 5-year survival rate and disease-free survival rate were 71% and 58%, respectively. Early consideration of liver transplantation before end-stage disease is crucial, as those with advanced cirrhosis experience more postoperative complications [5]. We decided to perform liver transplantation when serious biliary complications emerged, and the patient still had a good performance status, with preserved muscle mass, to ensure the procedure’s success and a faster recovery. Untreated AE is fatal in 70% to 90% of cases after 5 and 10 years of disease duration, highlighting the importance of timely recognition and optimal treatment [2].

Conclusions

Alveolar echinococcosis is a progressive and potentially fatal parasitic disease that can clinically and morphologically resemble primary liver malignancy. Establishing the etiology of hilar stenosis is often challenging, and in patients with negative biopsy and cytology results for malignant cells, AE should be included in the differential diagnosis. It is crucial to suspect AE early in the disease course, as complete surgical resection offers the possibility of a cure. Delayed diagnosis results in complications and unfavorable outcomes. Particularly severe clinical presentations with biliary and portal complications are indications for liver transplantation as a last therapeutic option, but with good outcomes. After radical resection and liver transplantation, continued therapy with albendazole is essential.