section name header

Basics ⬇

Basics

Definition

  • Cholangitis-bile duct inflammation.
  • Cholangiohepatitis-inflammation of bile ducts and surrounding liver parenchyma.
  • CCHS-more common in cats; histologically classified as suppurative, nonsuppurative (lymphoplasmacytic, lymphocytic), lymphoproliferative (transition to lymphosarcoma); or granulomatous.

Pathophysiology

  • Antecedent or coexisting conditions-inflammation or obstruction involving the extrahepatic bile duct (EHBDO) or pancreatic duct (cat), pancreatitis or IBD (dog, cat); CIN (cat).
  • Bacterial infection may be primary or secondary; cholestasis is permissive to bacterial infection.
  • Acute or chronic cholangitis-associates with bile duct hyperplasia, biliary epithelial hyperplasia, and a ductular reaction.
  • Chronic inflammation-may cause bile duct dystrophic mineralization or choleliths.
  • Suppurative disease-usually associated with positive bacterial culture or bacteria are observed cytologically (tissue or bile).
  • Nonsuppurative disease-immune mediated.
  • Sclerosing or destructive cholangitis-inflammation causing bile duct involution/destruction, immune-mediated or infectious-leads to ductopenia of small- and medium-sized bile ducts; a severe lesion.
  • Pyogranulomatous CCHS-infectious or immune mechanisms (dog or cat).
  • Lymphoproliferative disease-speculated transition stage of inflammation to neoplasia.

Systems Affected

  • Hepatobiliary-liver and biliary system
  • Gastrointestinal-pancreas and intestines

Incidence/Prevalence

Nonsuppurative CCHS-most common chronic liver disorder of the cat

Signalment

Species

Cat (common) and dog (uncommon)

Breed Predilections

Possibly Himalayan, Persian, Siamese cats

Mean Age and Range

  • Suppurative CCHS-range 0.4–16 years; but mostly young to middle-aged cats.
  • Nonsuppurative CCHS-range, 2–17 years; mostly middle-aged cats.

Predominant Sex

  • Suppurative CCHS-male cats predisposed
  • Nonsuppurative CCHS-none

Signs

General Comments

  • Suppurative CCHS-most severe clinical illness, acute onset often <5 days; abdominal pain, pyrexia; associated with EHBDO.
  • Nonsuppurative-ill >3 week (mo to yrs).

Historical Findings

CCHS-cyclic illness; chronic vague signs: lethargy, vomiting, anorexia, and weight loss; ductopenia (cats) if destructive cholangitis-polyphagic (reduced bile flow compromises nutrient assimilation, causing acholic stool, steatorrhea, and reduced uptake of fat-soluble substances, e.g. vitamin K1, essential fatty acids, vitamin E.

Physical Examination Findings

  • Suppurative CCHS-fever; painful abdomen; anicteric to jaundiced; dehydrated; shock.
  • Nonsuppurative CCHS-few physical abnormalities other than hepatomegaly; thickened intestines with IBD; variable jaundice, rare abdominal effusion.
  • Ductopenia (cats)-unkempt coat, variable lateral thoracoabdominal alopecia; acholic feces may vacillate with cyclic disease.

Causes

Suppurative CCHS

  • Bacterial infection-more common in cats: E coli, Enterobacter, Enterococcus, -hemolytic Streptococcus, Klebsiella, Actinomyces, Clostridia, Bacteroides; rare toxoplasmosis; dogs: usually enteric opportunists; rare Campylobacter, Salmonella, Leptospirosis, others.
  • May represent sequela to EHBDO or other cause of mechanical cholestasis.

Nonsuppurative CCHS

Concurrent disorders-cholecystitis, cholelithiasis, pancreatitis, EHBDO, and IBD (dogs, cats); and CIN (cats).

Risk Factors

  • Suppurative CCHS-EHBDO; cholelithiasis; cholestasis; infections elsewhere.
  • Feline nonsuppurative CCHS-IBD, pancreatitis, EHBDO, cholelithiasis, CIN.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnoses

  • Feline hepatic lipidosis (FHL)-may coexist; similar enzyme abnormalities and jaundice but low GGT unless concurrent biliary or pancreatic inflammation.
  • EHBDO and obstructive cholelithiasis; variable jaundice, increased ALP, GGT, and transaminase activities; increased cholesterol; US evidence of EHBDO.
  • Pancreatitis-may reflect cholelithiasis initiated CCHS in cats; lipemia, high cholesterol, and hyperbilirubinemia; inconsistent high fPLI, lipase, and amylase,, and ultrasound features; high fPLI implicates pancreatic inflammation but also may reflect IBD and duct inflammation.
  • Lymphoproliferative disease and lympho-sarcoma-may involve any enteric segment (thick wall), mesenteric lymphadenopathy; dense portal infiltrates spilling across the limiting plate; shares clinical features with CCHS; multisystemic lymphoma or lymphocytic leukemia may cause circulating “blast” cells; hepatic infiltrates may require immunohistochemical characterization.
  • Jaundice of septicemia-hyperbilirubinemia dominates clinical biochemical features, usually disproportionate to magnitude of liver enzyme activity.
  • Ductal plate malformations (DPM)-polycystic disease), (dogs, cats), especially Persian and Himalayan cats-normal or modestly increased liver enzymes; progressive peribiliary fibrosis in some DPM phenotypes (see Ductal Plate Malformations); variable mild suppurative or nonsuppurative portal aggregates, cholangitis, or CCHS.

CBC/Biochemistry/Urinalysis

CBC

  • Poikilocytes: common in cats with severe liver disease; non-regenerative anemia: anemia of chronic disease; Heinz body hemolysis: severely ill cats with low RBC GSH.
  • Suppurative CCHS-neutrophilic leukocytosis, left shift, toxic neutrophils. Nonsuppurative CCHS-may be normal, lymphoproliferative disorder or lymphoma may have lymphocytosis ± abnormal cell morphology.

Serum Biochemistry

  • Consistent findings-high ALT, AST, ALP, variable GGT; in cats higher enzymes in non-suppurative disease.
  • Variable findings-high total serum bile acids, bilirubin, and cholesterol: depends on severity and extent of cholestasis, coexistent illness, liver dysfunction.

Other Laboratory Tests

  • Species-specific PLI-may be high with pancreatitis and enteritis.
  • Vitamin B12-in cats low values indicate small bowel malabsorption (infiltrative disorders: IBD, lymphoma), pancreatic dysfunction, chronic oral antimicrobials causing bowel bacterial overgrowth.
  • Coagulation tests-variable; PT and PIVKA most sensitive for vitamin K1–induced coagulopathy.
  • T4-rules out hyperthyroidism as cause of liver enzyme activity in cats.

Imaging

  • Thoracic radiography-sternal lymphadeno-pathy suggests abdominal inflammation, general lymphadenopathy suggests lymphoma. Abdominal radiography-normal to large liver in nonsuppurative CCHS; rare mineralized choleliths or biliary structures in suppurative or nonsuppurative CCHS.
  • Abdominal ultrasonography-normal to large liver; thick bile duct or GB wall (inflammation, edema, infiltrates, fibrosis); echogenic intraluminal debris;; choleliths; focal parenchymal lesions (abscess, inflammation, neoplasia); lymphadenopathy (peripancreatic, perihilar hepatic, or mesenteric) suggests pancreatic, liver, intestinal inflammation or enteric neoplasia; hepatic parenchymal hyperechogenicity (concurrent FHL, inflammation, fibrosis); cysts (DPM, polycystic disease, cystadenoma); Note: no US lesions in some animals with severe CCHS.

Other Diagnostic Procedures

Fine-Needle Aspiration Cytology

  • Hepatic aspiration-for culture, identify FHL; cytology may reveal bacteria not visualized by light microscopy evaluation of biopsy. Note: cytology rules in FHL but is unreliable for diagnosis of nonsuppurative CCHS. Hepatocellular vacuolation is common in ill cats, may be misdiagnosed as FHL.
  • Cholecystocentesis-may reveal suppuration, bacteria, trematode eggs, or neoplasia. Normal bile is devoid of cells, blue amorphous appearance with Wright's Giemsa stain.

Percutaneous Biopsy

  • US-guided core-needle biopsy-may misdiagnose CCHS due to small sample size; need a minimum of 15 portal triads for accurate diagnosis; if 18-G core needle used, collect a minimum of 4 samples.
  • Inaccuracy with needle biopsy methods and biopsy of only a single liver lobe reflects differential lobe involvement and sample size.
  • Post-biopsy complications esp. cats: collapse, vasovagal due to biliary trauma, unintentional sampling of non-hepatic tissues with US needle sampling in cats.

Laparoscopy

  • Permits direct visualization of GB, porta hepatis, pancreas, and perihepatic and peripancreatic lymph nodes; permits biopsy of multiple liver lobes, as well as pancreas and bile collection (cholecystocentesis).
  • In EHBDO-avoid laparoscopy.

Laparotomy

Esp. if suspected EHBDO-recommended. Permits inspection of biliary structures; biliary decompression and biliary enteric anastomosis; biopsy of: liver, biliary structures, pancreas, intestines, lymph nodes, and cholecystocentesis.

Tissue Sampling

If nonsuppurative CCHS suspected, also biopsy bowel and pancreas.

Bile and Tissue Cultures

Aerobic and anaerobic bacterial cultures-of liver tissue and bile.

Molecular Genetics

Genetic test for feline polycystic disease may be appropriate.

Pathologic Findings

  • Suppurative CCHS-swollen liver, blunt edges, focal discolorations; may note erythematous, necrotic, or thick-walled GB (cholecystitis); peripancreatic steatonecrosis or fat saponification (pancreatitis); perihepatic and peripancreatic lymphadenopathy; EHBDO, may observe choleliths or cystic lesions (DPM).
  • Nonsuppurative CCHS-large to normal size firm liver (small in very chronic disease); blunt margins; variable surface irregularity, may observe choleliths or cystic lesions (DPM).
  • If concurrent FHL: yellow or pale friable parenchyma, samples float in formalin.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Inpatient Management

  • Suppurative CCHS with acute febrile illness, painful abdomen, left-shifted leukogram-hydration support, “best guess” bactericidal antimicrobials: initially based on cytology and Gram stain; start antibiotics if EHBDO or cholecystitis before surgery; continue antibiotics 4 weeks with choleretic therapy (ursodeoxycholic acid, SAMe) until enzymes normalize or signs resolve.
  • Nonsuppurative symptomatic cats-fluid therapy as necessary; if jaundiced: give vitamin K1 (0.5–1.5 mg/kg IM q12h for 3 doses) before invasive diagnostics and liver biopsy. Cats with CCHS-may need blood transfusion consequent to surgery or biopsy.
  • Polyionic fluids-supplement with B-soluble vitamins (2 mL/L), KCl, and K phosphate as needed; avoid dextrose supplements (see Hepatic Lipidoses).

Outpatient Management

  • Suppurative-after acute crisis managed.
  • Nonsuppurative-after resolution of acute crisis, provide life-long immunomodulation (if no bacteria observed or cultured), antioxidants, and hepatoprotectants.

Activity

Restricted while symptomatic.

Diet

Nutritional support-avoid FHL by feeding a balanced high-protein, high-calorie feline diet; supplement water-soluble vitamins; antigen-restricted diet if concurrent IBD; fat-restricted diet if severe ductopenia causing fat malabsorption, or chronic pancreatitis causing maldigestion; may require feeding tubes (esophagostomy preferred, jejunal feeding if symptomatic pancreatitis); rarely require parenteral nutrition (provoke FHL).

Client Education

Emphasize chronic nature of nonsuppurative CCHS and requirement for life-long therapy.

Surgical Considerations

  • Cholecystectomy-if cholecystitis.
  • Cholecystoenterostomy-may be necessary in patients with EHBDO which increases life-long risk for septic cholangitis. Cholelith removal.

Medications ⬆ ⬇

Medications

Drug(s)

Antibiotics for Suppurative CCHS

  • Bactericidal-against enteric opportunists; initially use combination of: ticarcillin or clavamox, enrofloxacin, combined with metronidazole (7.5–15 mg/kg PO q12h; low dose if jaundiced).
  • Modify initial or empiric antimicrobials based on culture and sensitivity reports. Resistant enterococcus-vancomycin (10 mg/kg q12h IV slow infusion for 7–10 days).

Immunomodulation: Nonsuppurative CCHS

  • Glucocorticoids-prednisolone (dogs: 2 mg/kg/day; cats: 4 mg/kg/day) for 14–21 days, taper to lowest effective alternate-day dose; chronic therapy usually needed; ensure prednisolone used in cats as prednisone is not bioavailable in this species; beware of development of diabetes mellitus in cats.
  • Metronidazole-combination with prednisolone, for cell-mediated immuno-modulation, antiendotoxin effect, and antibacterial, especially if IBD. Recent work implicates chronic bacterial involvement in nonsuppurative feline CCHS that may be attenuated by metronidazole.
  • Cats with confirmed ductopenia-require more aggressive immunomodulation; do not use azathioprine in cat; clinical experience suggests combination of prednisolone, metronidazole with pulsed methotrexate (see below) OR chlorambucil 1–2 mg per cat, load q24h for 3 days then every 3 days.
  • Methotrexate protocol feline nonsuppurative destructive or sclerosing CCHS: 0.4 mg total dose given in 3 divided doses on 1 day [0.13 mg total at 0, 12, and 24h] and repeated at 7–10 day intervals); may be given PO, IV, IM (parenteral routes require 50% dose reduction); concurrently provide folate (folinic acid) at 0.25 mg/kg daily. If lymphoproliferative or neoplastic infiltrates, use chemotherapy protocols developed for enteric lymphoma.

Antioxidants

  • Vitamin E (-tocopherol acetate)-10–30 IU/kg), high dose if chronic EHBDO or ductopenia PO because of fat malabsorption (see EHBDO for alternative form of Vitamin E that is water soluble).
  • S-adenosylmethionine (SAMe, use form with proven bioavailability and efficacy as a GSH donor)-20 mg/kg/day enteric-coated tablet PO 2h before feeding; many beneficial effects including anti-inflammatory influence that achieved remission in cats with mild nonsuppurative CCHS (without duct destruction).

Other

  • Ursodeoxycholic acid (UDCA)-10–15 mg/kg/day PO divided with food for best bioavailability; can formulate aqueous suspension (refrigerate); provides immunomodulatory, hepatoprotectant, choleretic, antifibrotic, and antioxidant effects. Recent information (humans with destructive cholangitis and knockout mouse models of such) indicate that UDCA may hasten small duct injury in destructive/sclerosing cholangitis. Thus, liver biopsy recommended before prescribing UDCA for cats with “suspected” chronic CCHS. Chronic UDCA in cats should be accompanied by taurine supplementation (250 mg/day) as all bile acids are obligatorily conjugated with taurine in cats.
  • B vitamin supplementation with thiamine (B1) and B12-thiamine 50–100 mg PO q24h for 3 days, then in water-soluble vitamin supplements; B12 (0.25–1.0 mg SC) if suspect gut malabsorption (use initial and sequential plasma B12 concentrations to verify need and efficacy of treatment; (some cats require weekly injections, then monthly).

Contraindications

Adjust drug dosages with regard to liver function and cholestasis. Caution with metronidazole to avoid neurotoxicity: if jaundiced use 7.5 mg/kg PO BID.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Nonsuppurative CCHS-initially monitor enzymes and bilirubin q7–14 days; after remission, assess quarterly; serum bile acid measurements complicated by ursodeoxycholic acid administration (detected by assay).

Prevention/Avoidance

Control IBD

Possible Complications

  • Suppurative CCHS may transform to nonsuppurative CCHS or sclerosing CCHS.
  • Diabetes mellitus in 30% of cats with sclerosing CCHS treated with prednisolone.
  • FHL may develop if inadequate nutritional intake or is induced by glucocorticoids.

Expected Course and Prognosis

  • Suppurative CCHS-may be cured.
  • Nonsuppurative CCHS-chronic, long-term remission possible (>8 years documented).

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Pancreatitis
  • Hepatic lipidosis
  • Polycystic liver disease
  • Lymphosarcoma
  • Lymphoproliferative disease
  • Cholangiocarcinoma-may develop in some cats with chronic nonsuppurative CCHS

Abbreviations

  • ALP = alkaline phosphatase
  • ALT = alanine aminotransferase
  • AST = aspartate amino transferase
  • CCHS = cholangitis/cholangiohepatitis syndrome
  • CIN = chronic interstitial nephritis
  • DPM = ductal plate malformation
  • EHBDO = extrahepatic bile duct obstruction
  • FHL = hepatic lipidosis
  • GB = gallbladder
  • GGT = gamma glutamyltransferase
  • GSH = glutathione
  • IBD = inflammatory bowel disease
  • PIVKA = proteins invoked by vitamin K absence
  • fPLI = feline pancreatic lipase activity
  • PT = prothrombin time
  • SAMe = S-adenosylmethionine
  • TLI = trypsin-like immunoreactivity
  • TPN = total parenteral nutrition
  • US = ultrasound

Author Sharon A. Center

Consulting Editor Sharon A. Center

Client Education Handout Available Online

Suggested Reading

Center SA. Diseases of the gallbladder and biliary tree. Vet Clin North Am Small Anim Pract 2009, 39:543–598.

Day M. Immunohistochemical characterization of the lesions of feline progressive lymphocytic cholangitis/cholangiohepatitis. J Comp Pathol 1998, 119:135–147.

Warren AE, Center SA, McDonough SE, et al. Histopathologic features, immunophenotyping, clonality and eubacterial FISH in cats with non-suppurative cholangitis/cholangiohepatitis. Vet Pathol 2011, 48:627–634.