Liver and biliary diseases affect more than a billion people worldwide, with high associated morbidity and mortality. The impact of the intestinal bacterial microbiome on liver diseases has been well established. However, the fungal microbiome, or mycobiome, has been overlooked for a long time. Recently, several studies have shed light on the role of the mycobiome in the development and progression of hepatobiliary diseases. In particular, the fungal genus Candida has been found to be involved in the pathogenesis of multiple hepatobiliary conditions. Herein, we compare colonisation and infection, describe mycobiome findings in the healthy state and across the various hepatobiliary conditions, and point toward communalities. We detail how quantitation of immune responses to fungal antigens can be employed to predict disease severity, e.g. using antibodies to Saccharomyces cerevisiae or specific anti-Candida albicans antibodies. We also show how fungal products (e.g. beta-glucans, candidalysin) activate the host's immune system to exacerbate liver and biliary diseases. Finally, we describe how the gut mycobiome can be modulated to ameliorate hepatobiliary conditions.

Fungal cholecystitis is an uncommon entity, and no cases of cholecystitis associated with mould infection have been reported. We present a case of acute Fusarium cholecystitis in a cytopenic patient with leukaemia who had disseminated fusariosis. We also review the published cases of fungal cholecystitis, which is most often caused by Candida species. Although it is rare, fungal cholecystitis should be part of the differential diagnosis of acute cholecystitis in high-risk patients with predisposing factors for opportunistic fungal infections.

We report a case of a previously healthy female patient who initially presented with fever, jaundice and right upper quadrant pain three days after dilatation and stenting of a stricture of the common bile duct (CBD). During an earlier admission, the patient had undergone endoscopic retrograde cholangiopancreatography (ERCP) having presented with fevers and biliary dilatation on ultrasound. The ERCP features were more consistent with Mirizzi's Syndrome. The patient subsequently underwent subtotal cholecystectomy and later developed a CBD stricture, requiring repeat ERCP and stent insertion. At presentation, she had moderately deranged liver function tests and significantly elevated inflammatory markers and was found on cross-sectional imaging to have developed a liver abscess. Aspiration of the lesion cultured Candida albicans She was treated with intravenous antifungals, broad-spectrum antibiotics and further aspiration of abscess, which contributed towards her successful recovery. Fungal liver abscess should be suspected in immunocompetent patients who undergo ERCP and or cholecystectomy.

Candida albicans is an important fungal pathogen that can cause life-threatening disseminated infections. To determine the efficacy of therapy in murine models, a determination of renal fungal burden as cfu is commonly used. However, this approach provides only a snapshot of the current situation in an individual animal and cryptic sites of infection may easily be missed. Thus, we aimed to develop real-time non-invasive imaging to monitor infection in vivo.

Bioluminescent C. albicans reporter strains were developed based on a bioinformatical approach for codon optimization. The reporter strains were analysed in vitro and in vivo in the murine model of systemic candidiasis.

Reporter strains allowed the in vivo monitoring of infection and a determination of fungal burden, with a high correlation between bioluminescence and cfu count. We confirmed the kidney as the main target organ but additionally observed the translocation of C. albicans to the urinary bladder. The treatment of infected mice with caspofungin and fluconazole significantly improved the clinical outcome and clearance of C. albicans from the kidneys; however, unexpectedly, viable fungal cells persisted in the gall bladder. Fungi were secreted with bile and detected in the faeces, implicating the gall bladder as a reservoir for colonization by C. albicans after antifungal therapy. Bile extracts significantly decreased the susceptibility of C. albicans to various antifungals in vitro, thereby probably contributing to its persistence.

Using in vivo imaging, we identified cryptic sites of infection and persistence of C. albicans in the gall bladder during otherwise effective antifungal treatment. Bile appears to directly interfere with antifungal activity.

Biliary candidiasis is increasing in the hospitalized immunosuppressed individuals. Placement of biliary stents in the cancer patients with obstructive jaundice has been found to be an important factor associated with infectious complications. Positive fungal cultures from bile should not be ignored as mere contamination but should be considered when prescribing treatment for the immunosuppressed with recurrent cholangitis or receiving long-term antibiotic therapy. Here,we report a case of cholangiocarcinoma with cholangitis where Candida tropicalis was the sole pathogen isolated from bile. This is probably the first case of its kind to be reported from Manipal, Karnataka, South India.

AAC caused by Candida is an uncommon entity usually seen in the critically ill. Here, we present the case of an 18-month-old renal transplant patient who developed candidal AAC during the post-operative period. Previous articles have addressed acalculous cholecystitis secondary to a variety of causes, or addressed a wide variety of Candida infections in the biliary tract, but this is the first discussion of cholecystitis caused by Candida without confounding factors such as biliary calculi or multiple pathogens. After the discussion of our patient's case, we also reviewed the English-language literature regarding candidal AAC and discussed diagnosis, treatment, and mortality.

Biliary obstruction and cholangitis are common problems in gastroenterology. Infections of the biliary tract with Candida and other fungal species have increasingly been seen in the last few years.

To investigate the prevalence, associations, and trends of biliary-tract candidiasis.

A prospective, observational, diagnostic study.

University Hospital, Muenster, Germany.

Consecutive patients undergoing ERCP for various indications.

In 54 of 123 patients, we found Candida species in bile samples (44%). In only 7 patients, candidiasis was suspected on endoscopy before mycologic proof. Only 4 of these 7 patients were correctly diagnosed with biliary candidiasis by simple morphologic aspects. The fungus was mainly differentiated as Candida albicans or Candida glabrata and rarely as Candida parapsilosis, Candida tropicalis, or other subspecies. Immunosuppression for various reasons was significantly associated with bile-duct candidiasis (P < .02). No significant association was found between positive fungal cultures and prior endoscopic sphincterotomy (P = .0824) or prior ERCP (P = .1152). Biliary candidiasis was neither associated with positive fungal cultures of buccal smears (P = .0722) nor with positive findings in stool samples (P = .0860).

Highly selected patient population. Buccal smears and stool samples were not obtained from all patients. Contamination artifacts cannot totally be excluded with the ERCP procedure.

Candida species very frequently can be detected in the bile. Positive fungal cultures of bile samples are not just contamination artifacts. This has to be taken into account when designing an anti-infectious treatment for recurrent cholangitis or even more cholangiosepsis. Especially in immunosuppressed patients or recipients of long-term antibiotic therapy, physicians should screen for biliary-tract candidiasis during endoscopic examination.

Candida biliary tract infection is a rare disease. Most of the reported cases have been diagnosed in patients with surgery or invasive procedures of the biliary tract, critical illness, immunosuppression or antibiotic treatment. This report deals with an 85 years old female patient with Candida albicans cholecystitis without previous risk factors and with a literature review on the subject. Only four patients without risk factors have been so far reported.

To generate and validate a predictive score of yeast isolation based on independent risk factors of yeast isolation in intensive care unit patients with peritonitis.

Retrospective cohort study to determine independent risk factors of yeast isolation, generation of the score, and validation in a prospective cohort of patients with peritonitis.

Tertiary-care, university-affiliated hospital.

Two hundred twenty-one patients with peritonitis hospitalized in a surgical intensive care unit between 1994 and 1999 for the retrospective cohort and 57 patients in the prospective cohort (2000).

Four independent risk factors of yeast isolation in peritoneal fluid (similar odds ratio) were found in the retrospective cohort: female gender, upper gastrointestinal tract origin of peritonitis, intraoperative cardiovascular failure, and previous antimicrobial therapy at least 48 hrs before the onset of peritonitis. A score based on the number of risk factors was constructed (grade A = zero or one risk factor, grade B = at least two risk factors, grade C = at least three risk factors, and grade D = four risk factors), and validated in the prospective cohort. For a grade C score, sensitivity was 84%, specificity was 50%, positive and negative predictive values were 67% and 72%, respectively, and overall accuracy was 71%.

Four independent risk factors of yeast isolation in the peritoneal fluid were identified in critically ill surgical patients with peritonitis. The presence of at least three of these factors (grade C score) was associated with a high rate of yeast detection. This approach could be helpful to initiate early antifungal therapy in this patient population.

Ascending bacterial cholangitis can be a recurring complication in older children and adolescents who have undergone successful surgery for biliary atresia. The authors describe a 19-year-old girl with a history of recurrent late-onset, febrile cholangitis in whom persistent jaundice developed. Aspergillus terreus was isolated from her biliary fluid obtained at percutaneous transhepatic cholangiography. Despite prolonged external biliary drainage and systemic amphotericin B therapy, the fungus was not eliminated from her biliary system. Aspergillus cholangitis can occur in the portoenterostomy patient and may be highly resistant to conventional therapy.

We report a case of spontaneous fungal peritonitis in a patient with cirrhosis. A 70-year-old woman with cirrhosis secondary to autoimmune hepatitis was admitted with fever and abdominal distention. Paracentesis revealed neutrocytosis, and despite appropriate antibacterial coverage, no clinical improvement was noted and the ascitic fluid white cell count increased on repeat paracentesis. Two consecutive ascitic fluid cultures grew Candida glabrata, and antifungal therapy with amphotericin was initiated, pending sensitivity of the isolate. Because of worsening renal function, amphotericin was discontinued and itraconazole was started, as sensitivity of the isolate was then available. Antifungal therapy resulted in resolution of ascitic fluid neutrocytosis and culture negativity. However, the patient's renal function continued to deteriorate, necessitating hemodialysis. Despite multiple courses of antibiotics, she died of fulminant sepsis and multiorgan failure.

Cholangitis is an infection of an obstructed biliary system, most commonly due to common bile duct stones. Bacteria reach the biliary system either by ascent from the intestine or by the portal venous system. Once the biliary system is colonized, biliary stasis allows bacterial multiplication, and increased biliary pressures enable the bacteria to penetrate cellular barriers and enter the bloodstream. Patients with cholangitis are febrile, often have abdominal pain, and are jaundiced. A minority of patients present in shock with hypotension and altered mentation. There is usually a leukocytosis, and the alkaline phosphatase and bilirubin levels are generally elevated. Noninvasive diagnostic techniques include sonography, which is the recommended initial imaging modality. Standard CT, helical CT cholangiography, and magnetic resonance cholangiography often add important information regarding the type and level of obstruction. Endoscopic sonography is a more invasive means of obtaining high-quality imaging, and endoscopic or percutaneous cholangiography offers the opportunity to perform a therapeutic procedure at the time of diagnostic imaging. Endoscopic modalities currently are favored over percutaneous procedures because of a lower risk of complication. Treatment includes fluid resuscitation and antimicrobial agents that cover enteric flora. Biliary decompression is required when patients do not rapidly respond to conservative therapy. Definitive therapy can be performed by a surgical, percutaneous, or endoscopic route; the last is favored because it is the least invasive and has the lowest complication rate. Overall prognosis depends on the severity of the illness at the time of presentation and the cause of the biliary obstruction.

The clinical significance of Candida spp isolated from the gallbladder on the biliary tract is relatively unknown.

To provide this information, patients with Candida spp isolated from gallbladder and other biliary tract sources during a 10-year period were identified through the records of our clinical microbiology laboratory. Medical records were analyzed for biliary disease causes, culture data, treatment, and outcome.

Twenty-seven patients were identified. Five of seven patients with cholecystitis were critically ill intensive care unit (ICU) patients in whom the mortality rate was 100%. Gallstone pancreatitis was found in four patients and was fatal in one patient with a pancreatic abscess and ongoing retroperitoneal sepsis. An external biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary obstruction. Cholangitis was present in 14 patients, and most bile cultures contained Candida as part of a mixed flora. Only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites.

(1) The ICU patient with Candida cholecystitis has a grave prognosis. (2) Patients with Candida isolated from biliary stents placed for obstruction and cholangitis should be treated with both antifungal and broad spectrum antimicrobial agents. (3) Candidemia is not frequently seen in this setting.