Skip to main content

Liver abscess caused by Clostridium perfringens after left hepatic trisectionectomy for perihilar cholangiocarcinoma: a case report



Clostridium perfringens sepsis has been reported to have a rapid onset and severe clinical outcome. We herein report a case of C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma.

Case presentation

A 72-year-old woman underwent left hepatic trisectionectomy for perihilar cholangiocarcinoma. Her postoperative course was uneventful except for bile leakage. She was discharged on postoperative day (POD) 35. On POD 54, she was readmitted because of abdominal pain with a high fever. Although her vital signs were stable on arrival at the hospital, a laboratory examination showed a severe inflammatory reaction and hemolysis, and she had developed disseminated intravascular coagulation. Abdominal contrast-enhanced computed tomography showed a 70-mm irregular shape and low-density containing air in liver segment 6, which suggested a liver abscess. The abscess was immediately drained of pus containing air. The pus showed multiple Gram-positive bacilli, and two blood cultures showed Gram-positive bacilli and hemolysis. Empirical antibiotic therapy with vancomycin and meropenem was started because C. perfringens was detected from the preoperative bile culture. Four hours after arrival, tachypnea and decreased oxygen saturation were observed. Her general condition deteriorated rapidly with significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Despite rapid drainage and empiric therapy, she died six hours after her arrival. At autopsy, the abscess consisted of coagulation necrosis of liver cells with inflammatory cell infiltration, and clusters of Gram-positive large bacilli were observed in the necrotic debris. C. perfringens was detected in the drainage fluid and blood culture. She was diagnosed with a liver abscess and severe sepsis caused by C. perfringens and treated promptly, but the disease progressed rapidly and led to her death.


Sepsis caused by C. perfringens can progress rapidly and lead to death in a few hours, so prompt treatment is needed. When patients who have undergone highly invasive hepatobiliary-pancreatic surgery show hemolysis and hepatic abscesses with gas, C. perfringens should be considered the most likely bacterium.


Clostridium perfringens is a bacterium generally found in the human gastrointestinal tract and genitourinary tract in healthy patients [1]. However, C. perfringens sepsis has been reported to have a rapidly worsening course and be potentially fatal in patients with immunosuppression [2]. We herein report a patient who developed C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma.

Case presentation

A 72-year-old woman was referred to our hospital for treatment of perihilar cholangiocarcinoma. She had no comorbidities other than hypertension and hyperlipidemia. Multidetector computed tomography (MDCT) demonstrated a 2 cm mass around the left hepatic duct with extensive vascular invasion. The lateral extension reached the confluence of the anterior and posterior branches of the bile duct, representing a Bismuth type IV tumor. The right hepatic artery was involved. The portal vein bifurcation was also involved with obstruction of the left portal vein (Fig. 1). She underwent endoscopic nasobiliary drainage (ENBD) to relieve jaundice, but subsequently developed cholangitis and was treated with antibiotic therapy based on the results of each culture (Fig. 2). The ENBD tube remained in place until the day of surgery (37 days). Cultures of bile from the ENBD tube obtained at each instance of cholangitis revealed Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterococcus faecium, Enterococcus casseliflavus, Bacteroides fragilis, and C. perfringens (Table 1). Given the tumor extension, patient’s general condition (performance status of 0), nutritional status (albumin, 3.8 g/dl), and liver function (indocyanine green clearance, 0.210 and 15-min retention rate, 4.3%), left hepatic trisectionectomy and caudate lobectomy with simultaneous resection of the portal vein and right hepatic artery were planned. Portal vein embolization was performed, and the subsequent remnant liver volume increased from 434 ml (41.9%) to 509 ml (47.5%). Five days prior to surgery, a decreased bile outflow from the ENBD tube and subsequent high fever were observed. We considered postponing the surgery, but since the fever was temporary, the decrease in the bile outflow was caused by the bending of the ENBD tube, and the outflow improved when the bending was released, and the blood tests on the day before surgery were generally within the acceptable range (WBC, 8010 μl; CRP: 1.99 mg/dl), we decided to proceed with the surgery as scheduled. The most recent preoperative bile cultures showed only Enterobacter cloacae. Therefore, CFPM was administered prophylactically, targeting this organism according to the infectious disease physician’s instructions. Surgery was performed with an operating time of 10 h 28 min and a blood loss of 2153 ml. (Fig. 3). Her postoperative course was almost uneventful except for bile leakage with International Study Group of Liver Surgery grade B. C. perfringens was not detected by ascites and bile culture after surgery. Findings from blood tests 2 days before discharge were generally acceptable (WBC, 7640/μl; CRP, 2.65 mg/dl; albumin, 2.6 g/dl). She was discharged on postoperative day (POD) 35 (Fig. 2). The tumor was pT4 N0 M0 pStage IIIB according to the UICC 8th guidelines [3].

Fig. 1
figure 1

Preoperative contrast-enhanced computed tomography findings. The tumor (T) was mainly located in the left hepatic duct (a) and involved the right hepatic artery and the portal vein (b). T tumor, B2 segment 2 branch of the bile duct, Bant anterior branch of the bile duct, Bpost posterior branch of the bile duct, RHA right hepatic artery, RPV right portal vein

Fig. 2
figure 2

Clinical course. The blue dotted line represents the white blood cell (WBC) count (right y-axis), and the yellow line represents the C-reactive protein (CRP) level (left y-axis). The patient required hospitalization and antibiotic therapy to treat preoperative cholangitis, postoperative bile leakage, and postoperative liver abscess. The numbers of “cultures of bile or drainage fluid” correspond to Table 1. TAZ/PIPC tazobactam/piperacillin, LVFX levofloxacin, CFPM cefepime, ABPC ampicillin, CMZ cefmetazole, MEPM meropenem, VCM vancomycin

Table 1 Microorganisms isolated from perioperative bile or drainage fluid culture
Fig. 3
figure 3

Intraoperative picture after removal of the specimen. PV portal vein, RHA right hepatic artery

Nineteen days after discharge (POD 54), she was readmitted due to acute-onset abdominal pain, massive hematuria, and high fever from the previous day. On arrival at the hospital, although her vital signs were stable, a laboratory examination showed a severe inflammatory reaction and hemolysis, which suggested disseminated intravascular coagulation (DIC) with an International Society on Thrombosis and Hemostasis DIC score of 7 (Table 2). Abdominal contrast-enhanced CT showed a liver abscess 70 mm in size in segment 6 (Fig. 4), and ultrasonically guided drainage was performed immediately. The abscess was drained of 250 mL of air-filled pus. Multiple Gram-positive bacilli were detected in the pus. Two blood cultures showed Gram-positive bacilli and hemolysis. Based on the strong hemolytic findings, empiric antibiotic therapy (vancomycin: 750 mg/day, meropenem: 3 g/day) was started, targeting C. perfringens and β-hemolytic streptococci.

Table 2 Laboratory result at readmission
Fig. 4
figure 4

Contrast-enhanced computed tomography findings on POD 54. A liver abscess 70 mm in size was found in segment 6. There was no intrahepatic bile duct dilatation or ischemic areas in the remnant liver

Four hours after her arrival, however, tachypnea and decreased oxygen saturation appeared. A laboratory examination showed significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Five hours after her arrival, she presented with sudden cardiopulmonary arrest, and cardiopulmonary resuscitation (CPR) was started. Despite CPR being performed for one hour, she died six hours after her arrival.

At autopsy, an abscess 32 × 22 mm in size was observed in liver segment 6 (Fig. 5a). Microscopically, the abscess consisted of coagulation necrosis of liver cells with acute inflammatory cell infiltration and a cavity (Fig. 5b). Clusters of basophilic, Gram-positive large bacilli were observed in the necrotic debris in the cavity (Fig. 5c, d). C. perfringens was detected in the drainage fluid. No ischemic changes due to reconstructed vessel occlusion were observed in the remnant liver. There were no findings of anastomotic leakage at the hepaticojejunostomy. No abscesses were found in any other organs. In summary, the autopsy, along with the clinical, laboratory, and microbiological data, revealed serious C. perfringens infection characterized by liver abscesses, sepsis, and DIC.

Fig. 5
figure 5

a Macroscopic findings of the autopsy liver. A large abscess 32 × 22 mm in size is seen in liver segment 6. bd Microscopic findings of the liver abscess. The abscess is composed of coagulation necrosis of liver cells at the periphery and a central cavity with necrotic debris containing many basophilic, Gram-positive large bacilli


C. perfringens is reported to cause cholecystitis, liver abscess, intrauterine infection, and pyelonephritis. Alpha toxin, which is the most important exotoxin produced by C. perfringens, can lyse host cell membranes [4]. This reaction causes many pathological processes, such as tissue necrosis, localized edema, electrolyte disturbance, DIC, severe hemolysis, and multiple organ failure [5]. C. perfringens sepsis is thus considered to have a poor prognosis, often being associated with shock and death. The mortality rate of patients with sepsis caused by C. perfringens has been reported to be approximately 70–80%, with a 30-day mortality rate of 27–44%. The median time to death from C. perfringens is approximately 9.7 h [6]. Indeed, in our patient, despite prompt drainage being performed, sepsis and hemolysis had already developed at the time of arrival, and the duration from arrival to death was only approximately 6 h.

C. perfringens is isolated from bile in 4.3% of severe bile duct infections [7]. Sepsis caused by C. perfringens rarely occurs in healthy individuals and is more likely to occur in patients with some risk factors, such as advanced age, poorly controlled diabetes, liver cirrhosis, malignancies, surgery, and immunosuppression [8,9,10]. In the present case, in addition to highly invasive surgery, perioperative complications requiring prolonged perioperative antibiotic therapy for preoperative cholangitis and postoperative bile leakage were assumed to be associated with the development of sepsis due to C. perfringens. Prolonged perioperative antibiotic therapy leads to the emergence of drug-resistant bacteria and dysbiosis, which directly impact the immune response balance [11]. Therefore, it was necessary to recognize that the patient remained a so-called “compromised host” and to urge her to be alert for physical changes, even after the early postoperative complications recovered. In addition, in retrospect, CT should have been performed one month before discharge, as some signs of liver abscess might have been detected if we had done so.

Liver abscess can occur via the bile ducts or vessels (arterial or portal) or directly. In our case, there were no clinical findings suggesting enteritis. Neither CT nor autopsy findings indicated enteritis, residual abscess, hepatic ischemia and infarction, or stricture of the hepatojejunal anastomosis. Therefore, bile stasis due to retrograde cholangitis was considered the main cause of subsequent liver abscess and sepsis. Retrograde cholangitis is one of the most common complications in patients after surgery with bile duct reconstruction [12,13,14]. It is common practice to reference previous culture findings when selecting antibiotic agents [12, 13]. However, while several culture studies were performed, C. perfringens was detected only once before surgery and was not found in the latest culture. Prolonged antibiotic therapy may have contributed to the difficulty in detecting C. perfringens.

Between 2000 and 2022, 16 sepsis cases were reported in PubMed with the keywords “Clostridium perfringens”, “sepsis”, and “postoperative”. Table 3 shows the reported cases of sepsis caused by C. perfringens after hepatobiliary-pancreatic surgery [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], including our case. The median age was 66 (range 52–82) years old. Nine patients (50%) had comorbid diseases, including 4 (44%) with diabetes mellitus and 11 (69%) with malignant diseases. The operative procedure included pancreatectomy, liver resection, liver transplantation, and cholecystectomy, and 8 patients received bile duct reconstruction. The timing of the onset after surgery has varied among cases. Eight cases (50%) were diagnosed more than 1 month after surgery, while 1 occurred more than 20 years later. Seven cases (44%) were fatal, and 4 (25%) died within 6 h of the diagnosis. Nine cases (53%) required drainage. Whether C. perfringens has been detected previously in these reported cases is unclear. However, even in the absence of previous detection, when hemolysis or abscesses with gas are found, treatment should be initiated promptly, keeping C. perfringens in mind.

Table 3 Reported cases of sepsis caused by C. perfringens after hepatobiliary-pancreatic surgery


Sepsis caused by C. perfringens can progress rapidly and lead to death in a few hours. When patients develop hemolysis and air-filled liver abscesses after highly invasive hepatobiliary-pancreatic surgery, especially combined bile duct reconstruction, C. perfringens should be considered a potential cause and should receive prompt multidisciplinary treatment.

Availability of data and materials

All data analyzed in this study are included in this manuscript.



Multidetector computed tomography


Endoscopic nasobiliary drainage

UICC 8th:

The Union for International Cancer Control classification 8th edition


Postoperative day


Disseminated intravascular coagulation


Cardiopulmonary resuscitation


  1. Suzaki A, Ohtani K, Komine-Aizawa S, Matsumoto A, Kamiya S, Hayakawa S. Pathogenic characterization of Clostridium perfringens strains isolated from patients with massive intravascular hemolysis. Front Microbiol. 2021;12: 713509.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kurasawa M, Nishikido T, Koike J, Tominaga S, Tamemoto H. Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient. World J Diabetes. 2014;5(2):224–9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Brierley JD, Gospodarwicz MK, editors. CW. UICC: TNM Classification of malignant tumors. 8th edn. Wiley; 2017.

  4. Sakurai J, Nagahama M, Oda M. Clostridium perfringens alpha-toxin: characterization and mode of action. J Biochem. 2004;136(5):569–74.

    Article  CAS  PubMed  Google Scholar 

  5. Chinen K. Sudden death caused by Clostridium perfringens sepsis presenting as massive intravascular hemolysis. Autops Case Rep. 2020;10(3): e2020185.

    Article  PubMed  PubMed Central  Google Scholar 

  6. van Bunderen CC, Bomers MK, Wesdorp E, Peerbooms P, Veenstra J. Clostridium perfringens septicaemia with massive intravascular hemolysis: a case report and review of the literature. Neth J Med. 2010;68(9):343–6.

    PubMed  Google Scholar 

  7. Gomi H, Takada T, Hwang TL, Akazawa K, Mori R, Endo I, et al. Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis. J Hepatobiliary Pancreat Sci. 2017;24(6):310–8.

    Article  PubMed  Google Scholar 

  8. Yamamoto Y, Itoh N, Sugiyama T, Kurai H. Clinical features of Clostridium bacteremia in cancer patients: a case series review. J Infect Chemother. 2020;26(1):92–4.

    Article  CAS  PubMed  Google Scholar 

  9. Fujita H, Nishimura S, Kurosawa S, Akiya I, Nakamura-Uchiyama F, Ohnishi K. Clinical and epidemiological features of Clostridium perfringens bacteremia: a review of 18 cases over 8 year-period in a tertiary care center in metropolitan Tokyo area in Japan. Intern Med. 2010;49(22):2433–7.

    Article  PubMed  Google Scholar 

  10. Shindo Y, Dobashi Y, Sakai T, Monma C, Miyatani H, Yoshida Y. Epidemiological and pathobiological profiles of Clostridium perfringens infections: review of consecutive series of 33 cases over a 13-year period. Int J Clin Exp Pathol. 2015;8(1):569–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lobo LA, Benjamim CF, Oliveira AC. The interplay between microbiota and inflammation: lessons from peritonitis and sepsis. Clin Transl Immunol. 2016;5(7): e90.

    Article  Google Scholar 

  12. Ito Y, Abe Y, Kitago M, Itano O, Kitagawa Y. Predictive factors of late cholangitis in patients undergoing pancreaticoduodenectomy. World J Surg Oncol. 2018;16(1):19.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ueda H, Ban D, Kudo A, Ochiai T, Tanaka S, Tanabe M. Refractory long-term cholangitis after pancreaticoduodenectomy: a retrospective study. World J Surg. 2017;41(7):1882–9.

    Article  PubMed  Google Scholar 

  14. Ruzzenente A, Alaimo L, Caputo M, Conci S, Campagnaro T, De Bellis M, et al. Infectious complications after surgery for perihilar cholangiocarcinoma: a single Western center experience. Surgery. 2022.

    Article  PubMed  Google Scholar 

  15. Leeda M, van der Sloot JA. Massive hemolysis: a rare manifestation of sepsis due to Clostridium perfringens. Ned Tijdschr Geneeskd. 2006;150(34):1895–8.

    CAS  PubMed  Google Scholar 

  16. Lochman P, Kabelác K, Pospísil I, Dobes D, Cáp R. Clostridial sepsis and gas gangrene of the abdominal wall after cholecystectomy. Cas Lek Cesk. 2007;146(7):614–6.

    CAS  PubMed  Google Scholar 

  17. Tabarelli W, Bonatti H, Cejna M, Hartmann G, Stelzmueller I, Wenzl E. Clostridium perfringens liver abscess after pancreatic resection. Surg Infect. 2009;10(2):159–62.

    Article  Google Scholar 

  18. Jandík J, Vokůrka J. A necrotizing fasciitis of an abdominal wall after a cholecystectomy—a case report. Rozhl Chir. 2009;88(1):27–31.

    PubMed  Google Scholar 

  19. Diaz GC, Boyer T, Renz JF. Survival of Clostridium perfringens sepsis in a liver transplant recipient. Liver Transpl. 2009;15(11):1469–72.

    Article  PubMed  Google Scholar 

  20. Juntermanns B, Radunz S, Heuer M, Vernadakis S, Reis H, Gallinat A, et al. Fulminant septic shock due to Clostridium perfringens skin and soft tissue infection eight years after liver transplantation. Ann Transplant. 2011;16(3):143–6.

    Article  CAS  PubMed  Google Scholar 

  21. Watt J, Amini A, Mosier J, Gustafson M, Wynne JL, Friese R, et al. Treatment of severe hemolytic anemia caused by Clostridium perfringens sepsis in a liver transplant recipient. Surg Infect. 2012;13(1):60–2.

    Article  Google Scholar 

  22. Qandeel HA, Hammad A, Ray C, Sajid M, Mahmud S. Clostridium perfringens sepsis and liver abscess following laparoscopic cholecystectomy. J Surg Case Rep. 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kitterer D, Braun N, Jehs MC, Schulte B, Alscher MD, Latus J. Gas gangrene caused by Clostridium perfringens involving the liver, spleen, and heart in a man 20 years after an orthotopic liver transplant: a case report. Exp Clin Transplant. 2014;12(2):165–8.

    PubMed  Google Scholar 

  24. Martí Gelonch L, Jiménez Agüero R, Rodríguez Canas N, EnríquezNavascués JM. Massive hemolysis due to sepsis caused by Clostridium perfringens secondary to liver abscess. Presentation of two cases with a similar history. Gastroenterol Hepatol. 2018;41(9):562–3.

    Article  PubMed  Google Scholar 

  25. Ono R, Kashiwagi H, Kawachi J, Isogai N, Miyake K, Murata T, et al. Successful treatment of hepatic gas gangrene by open drainage: a case report and review of the Japanese literature. Int J Surg Case Rep. 2018;49:121–5.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hamura R, Haruki K, Kumagai Y, Shiba H, Wakiyama S, Yanaga K. Subphrenic abscess due to Clostridium perfringens after hepatic resection for hepatocellular carcinoma following emphysematous cholecystitis: report of a case. Int J Surg Case Rep. 2020;67:86–90.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dahl SS, Thorsteinsson M, Lambine TL, Penninga L. Severe sepsis caused by a gas-forming Clostridium perfringens and Klebsiella variicola liver abscess following total pancreatectomy. BMJ Case Rep. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Takahashi G, Nakamura Y, Hayakawa T, Ono T, Endo K, Yoshida H. Clostridium perfringens sepsis after pancreatoduodenectomy: a case report. Surg Case Rep. 2022;8(1):48.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Itoh N, Akazawa N, Yanaidani T, Kuwahara T. Clinical and microbiological features of intratumor abscess with bloodstream infection caused by Plesiomonas shigelloides, Citrobacter freundii, Streptococcus mitis/oralis, Clostridium perfringens, and Candida albicans in a patient with cholangiocarcinoma: a case report. J Infect Chemother. 2022;28(12):1677–81.

    Article  PubMed  Google Scholar 

Download references


We acknowledge all people who were involved in this study.


No grant support or funding from public institutions or private enterprises was received for this case report.

Author information

Authors and Affiliations



YT drafted the manuscript. MY supervised the writing of the manuscript. KO and TS were involved in performing the surgery. MY, SO, KO, RA, and TS contributed to patient management. HK contributed to infection control. HY and TS performed the autopsy and made a pathological diagnosis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mihoko Yamada.

Ethics declarations

Ethics approval and consent to participate

All ethical and moral issues have been considered in this study.

Consent for publication

Written informed consent for the publication of this case report and the accompanying images was obtained from the patient.

Competing interests

The authors have no competing interests to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tohmatsu, Y., Yamada, M., Otsuka, S. et al. Liver abscess caused by Clostridium perfringens after left hepatic trisectionectomy for perihilar cholangiocarcinoma: a case report. surg case rep 9, 111 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: