Pyogenic Hepatic Abscesses

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Background

Pyogenic hepatic abscesses are uncommon conditions that present diagnostic and therapeutic challenges to physicians. If left untreated, these lesions are invariably fatal.

Liver abscesses[1] have been recognized since the age of Hippocrates. In 1883, Koch described amebae as a cause of liver abscess. In 1938, Ochsner and Debakey published the largest series of pyogenic and amebic liver abscesses in the literature.[2]  Since the late 20th century, percutaneous drainage has become a useful therapeutic option.[3, 4, 5, 6, 7]

Pathophysiology

Pyogenic bacteria can gain access to the liver through direct extension from contiguous organs or via the portal vein or hepatic artery. Hepatic clearance of bacteria via the portal system appears to be a normal phenomenon in healthy individuals; however, organism proliferation, tissue invasion, and abscess formation can occur with biliary obstruction, poor perfusion, or microembolization.

Microbiology

The organisms isolated most often are included below. Most abscesses contain more than one organism and frequently are of biliary or enteric origin. Blood culture results are positive in 33-65% of cases,[8] with positive results from abscess cultures reported in 73-100% of series.[8, 9]  Escherichia coli is the most commonly isolated organism in Western series, whereas Klebsiella pneumoniae has emerged as a common isolate in patients with diabetes in Taiwan.[10, 11, 12, 13, 14]

The microorganisms most commonly isolated from blood and abscess cultures are as follows[8, 9] :

Etiology

Biliary disease

Biliary disease accounts for 21-30% of reported cases of pyogenic hepatic abscess.[4, 8, 15, 9] Extrahepatic biliary obstruction leading to ascending cholangitis and abscess formation is the most common cause[8, 9] and is usually associated with choledocholithiasis, benign and malignant tumors,[5] or postoperative strictures.

Biliary-enteric anastomoses (choledochoduodenostomy or choledochojejunostomy) have also been associated with a high incidence of liver abscesses.[3, 9] Biliary complications (eg, stricture, bile leak) after liver transplantation are also recognized causes of pyogenic liver abscesses.

Infection via portal system (portal pyemia)

The infectious process originates within the abdomen and reaches the liver via embolization or seeding of the portal vein. With the liberal use of antibiotics for intra-abdominal infections, portal pyemia is now a less frequent cause of pyogenic liver abscesses, but it still accounts for 20% of cases.[8] Appendicitis and pylephlebitis are the predominant causes. However, any source of intra-abdominal abscess, such as acute diverticulitis, inflammatory bowel disease, and perforated hollow viscus, can lead to portal pyemia and hepatic abscesses.

Hematogenous (via hepatic artery)

This infectious process results from seeding of bacteria into the liver in cases of systemic bacteremia from bacterial endocarditis or urinary sepsis or as a consequence of intravenous drug abuse.[5]

Blunt or penetrating trauma and liver necrosis from inadvertent vascular injury during laparoscopic cholecystectomy are recognized causes of liver abscess.[8]  In addition, transarterial embolization and cryoablation of liver masses are now recognized as new etiologies of pyogenic abscesses.[16]  A study by Tsai et al found recent upper gastrointestinal panendoscopy to be associated with an increased risk of pyogenic hepatic abscess.[17]

Cryptogenic

No cause is found in approximately half of the cases. However, the incidence is increased in patients with diabetes or metastatic cancer. Patients with repeated cryptogenic liver abscesses should undergo biliary and gastrointestinal evaluation.[8]

Epidemiology

The incidence of pyogenic liver abscess has changed little since just before the mid-20th century. In the United States, the incidence of pyogenic liver abscess is estimated to be 8-15 cases per 100,000 persons. This figure is considerably higher in countries where health care is not readily available. Studies indicate that the male-to-female ratio is approximately 2:1; the problem occurs most commonly in the fourth to sixth decade of life.[8]

Prognosis

When left untreated, pyogenic liver abscess is associated with a mortality of 100%. Early series reported mortalities higher than 80%. With early diagnosis, appropriate drainage, and long-term antibiotic therapy, the prognosis has improved markedly[15] ; mortality is now in the range of 15-20%.[9, 18]  Poor prognostic factors are as follows:

Lo et al performed a retrospective study of 741 patients with pyogenic hepatic abscesses with the aim of identifying risk factors associated with treatment failures.[22]  Findings included the following:

The neutrophil-to-lymphocyte ratio has been suggested as a potentially useful prognostic marker for pyogenic hepatic abscess in the emergency department.[23]

History

The clinical presentation of liver abscess is insidious; many patients have symptoms for weeks before presentation. Fever and right-upper-quadrant (RUQ) pain are the most common complaints. Pain is reported in as many as 80% of patients and may be associated with pleuritic chest pain or right shoulder pain. Symptoms are often misdiagnosed as acute cholecystitis. Fever occurs in 87-100% of patients and is usually associated with chills and malaise.[9, 24]  Anorexia, weight loss, and mental confusion are also common symptoms.

Physical Examination

Physical examination findings are most notable for RUQ tenderness. Hepatomegaly, liver mass, and jaundice are also common. Occasionally, patients may present with rales, pleural effusion, friction rub, or pulmonary consolidation. Rarely, patients are admitted with sepsis and peritonitis from intraperitoneal rupture of the abscess. The signs and symptoms of pyogenic liver abscess are summarized in Table 1 below.[9, 24]

Table 1. Symptoms and Signs of Pyogenic Liver Abscess[9, 24]



View Table

See Table

Complications

The complications of pyogenic hepatic abscess result from rupture of the abscess into adjacent organs or body cavities. They may be broadly divided into pleuropulmonary and intra-abdominal types.

Pleuropulmonary complications are the most common and have been reported in 15-20% of early series. These include pleurisy and pleural effusion, empyema, and bronchohepatic fistula.[2]  Intra-abdominal complications are also common. They include subphrenic abscess and rupture into the peritoneal cavity, stomach, colon, vena cava, or kidney. A large abscess compressing the inferior vena cava and the hepatic veins may result in Budd-Chiari syndrome. Rupture into the pericardium or brain abscess from hematogenous spread is rare.

Pyogenic liver abscess has been associated with increased risk of acute kidney injury[25]  and acute pancreatitis.[26]

Laboratory Studies

A complete blood count (CBC) should be obtained. Anemia is observed in 50-80% of patients.[8, 9] Leukocytosis of more than 10,000/μL is observed in 75-96% of patients.[8, 9] Bands of more than 10% are observed in 40% of patients.

The erythrocyte sedimentation rate (ESR) is commonly elevated.

Liver function tests are helpful. An elevated alkaline phosphatase (ALP) level[4] is observed in 95-100% of patients.[8, 9] An elevated serum aspartate aminotransferase (AST) level, an elevated serum alanine aminotransferase (ALT) level, or both are observed in 48-60% of patients. An elevated bilirubin level[15] is observed in 28-73% of patients.[8, 9] A decreased albumin level (< 3 g/dL) and an increased globulin value (>3 g/dL) are frequently observed.

The prothrombin time (PT) is elevated in 71-87% of patients.[15]

Imaging Studies

Although chest and abdominal radiographs are nonspecific, they are frequently obtained at the initial evaluation. Chest radiography findings are abnormal in approximately half the patients. Nonspecific findings may include an elevated right hemidiaphragm, subdiaphragmatic air-fluid level, pneumonitis, consolidation, and pleural effusion. If gas-forming organisms are present, the abdominal x-ray film might show evidence of intrahepatic air, portal venous gas, air-fluid levels, or air in the biliary tree.

Radionucleotide sulfur colloid scanning has been completely supplanted by computed tomography (CT) and ultrasonography (US). Findings can help reliably detect masses larger than 2 cm. The sensitivity of the findings ranges from 50-80%; however, they lack specificity.

Real-time US findings are 80-100% sensitive.[6, 9, 18, 27, 28, 29] A round or oval hypoechoic mass is consistent with pyogenic abscess.

CT has become the imaging study of choice for detecting liver lesions.[6, 9, 18, 27, 28, 29] Pyogenic liver abscesses are not enhanced on images after intravenous contrast administration. Triphasic CT with arterial and portal venous phases helps define the proximity of the abscess to the major branches of the portal and hepatic veins. Findings have sensitivity similar to that of US, but they lack specificity. (See the image below.)



View Image

CT scan of liver abscess reveals large, septated abscess of right hepatic lobe. Abscess was successfully treated with percutaneous drainage and antimi....

Procedures

Diagnostic aspiration is performed under US or CT guidance[9, 18]  and is usually followed by drainage catheter placement. The aspirate is sent for culture and cytology.

Approach Considerations

The most dramatic change in the treatment of pyogenic liver abscess to date was the emergence of computed tomography (CT)-guided drainage. Before this development, open surgical drainage was the treatment most often employed, with mortality figures as high as 70%. If the abscess is multiloculated, multiple catheters might be needed to achieve adequate drainage.

Although at present, most liver abscesses are treated with antibiotics and catheter drainage under the guidance of ultrasonography (US) or CT, surgical drainage is still indicated in some cases. Indications for surgical drainage include the following:

Relative contraindications for surgery include the following:

The current accepted approach includes the following three steps:

A retrospective cohort study by Ke et al provided preliminary evidence to suggest that radiofrequency (RF) ablation (RFA) is a safe, feasible, and effective treatment for huge multiloculated pyogenic hepatic abscesses and that it should be considered as a therapeutic alternative for patients with such abscesses who are unresponsive to or unsuitable for percutaneous drainage plus antibiotics and who refuse surgical intervention.[31]

Antibiotic Therapy

Diagnostic aspiration should be performed as soon as possible. The antimicrobial agent should provide adequate coverage against aerobic gram-negative bacilli, microaerophilic streptococci, and anaerobic organisms, including Bacteroides fragilis. Usually, a combination of two or more antibiotics is given.

Metronidazole and clindamycin have wide anaerobic coverage and provide excellent penetration into the abscess cavity. A third-generation cephalosporin or an aminoglycoside provides excellent coverage against most gram-negative organisms. Fluoroquinolones are an acceptable alternative in patients who are allergic to penicillin. This modality has been shown to be effective in patients with unilocular abscesses that are smaller than 3 cm.[32]

Percutaneous Drainage

Diagnostic aspiration should be performed as soon as the diagnosis is made. It can be performed under the guidance of US[24, 33]  (if small or superficial) or CT and is usually followed by placement of a drainage catheter. Multiple abscesses necessitate CT-guided drainage.[24]

Once positioned, the catheter should be irrigated with isotonic sodium chloride solution and placed to allow gravity drainage. The drain is removed when the abscess cavity collapses, as confirmed by CT. Presence of ascites and proximity to vital structures are contraindications for percutaneous drainage. Coagulopathy can be corrected with transfusion of fresh frozen plasma prior to drainage.

The success rate of percutaneous drainage is in the range of 80-87%.[3]  Percutaneous drainage should be considered to have failed if no improvement occurs, if the condition worsens within 72 hours of drainage, or if the abscess recurs despite adequate initial drainage. Failure of percutaneous drainage can be treated by either inserting a second catheter or performing open surgical drainage.

Surgical Drainage

Surgical drainage was once considered to be the criterion standard in treating liver abscesses.[34] Currently, it is indicated for the following:

The presence of peritoneal signs in a patient with pyogenic liver abscess mandates emergency laparotomy because free rupture of the abscess into the peritoneal cavity may have occurred.

Liver resection should be considered when the following are present:

Operative details

Open drainage of pyogenic liver abscess may be accomplished via three approaches, as follows:

Before the antibiotic era, the extraperitoneal approach was often used to avoid contamination of the peritoneal cavity. Currently, with the availability of broad-spectrum antibiotics, the transperitoneal approach is safe and is considered the preferred approach because it allows thorough inspection of the peritoneal cavity and permits the mobilization necessary for adequate drainage.

Hepatic resection has been advocated in situations where drainage and antibiotics are unlikely to be curative. Examples include secondary infection of a hepatic malignancy and hepatic abscesses associated with chronic granulomatous diseases of childhood. A necrotic right lobe from vascular injury during laparoscopic cholecystectomy, with recurrent abscesses secondary to intrahepatic biliary strictures, is another situation that could necessitate a partial hepatectomy.

Laparoscopic drainage

Now that practitioners have gained greater increased experience with the laparoscopic approach to liver lesions, laparoscopic drainage of pyogenic hepatic abscesses is being performed safely, and the time required to carry out the procedure has been reduced.[35, 36, 37]

The laparoscopic approach eliminates access trauma and can help detect predisposing pathology. Intraoperative laparoscopic US can accurately detect the location of the abscess to allow drainage under US guidance. There is evidence to suggest that it is a relatively safe alternative,[37, 38]  and as experience with this use of the laparoscope increases, its application to the management of hepatic abscess will continue to evolve.[16, 35]

Complications

Complications of percutaneous drainage include perforation of adjacent abdominal organs, pneumothorax, hemorrhage, and leakage of the abscess cavity into the peritoneum. Immunocompromised patients with multiple diffuse microabscesses are not candidates for either percutaneous or open surgical drainage and are best treated with high-dose antibiotics. Such patients have the highest mortality.

Author

Todd A Nickloes, DO, FACOS, Associate Professor, Department of Surgery, Division of Trauma/Critical Care, University of Tennessee Medical Center-Knoxville

Disclosure: Nothing to disclose.

Coauthor(s)

Brian Reed, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center

Disclosure: Nothing to disclose.

LaMar O Mack, MD, Resident Physician, Department of Surgery, University of Tennessee Medical Center

Disclosure: Nothing to disclose.

Mohamed Akoad, MD, Liver Transplant Surgeon, Division of Hepatobiliary and Liver Transplantation, Department of Surgery, Veterans Administration Pittsburgh Healthcare System

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

David L Morris, MD, PhD, FRACS, Professor, Department of Surgery, St George Hospital, University of New South Wales, Australia

Disclosure: Received none from RFA Medical for director; Received none from MRC Biotec for director.

Chief Editor

John Geibel, MD, MSc, DSc, AGAF, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Richard W Golub, MD, FACS Consulting Surgeon, Sarasota Memorial Hospital and Doctors Hospital; Consulting Surgeon, Intercoastal Medical Group

Richard W Golub, MD, FACS is a member of the following medical societies: American College of Gastroenterology, American College of Surgeons, American Society for Gastrointestinal Endoscopy, American Society of Colon and Rectal Surgeons, Association for Academic Surgery, Association for Surgical Education, Crohns and Colitis Foundation of America, Society for Surgery of the Alimentary Tract, and Society of American Gastrointestinal and Endoscopic Surgeons

Disclosure: Nothing to disclose.

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CT scan of liver abscess reveals large, septated abscess of right hepatic lobe. Abscess was successfully treated with percutaneous drainage and antimicrobial therapy. Image courtesy of Michelle V Lisgaris, MD.

CT scan of liver abscess reveals large, septated abscess of right hepatic lobe. Abscess was successfully treated with percutaneous drainage and antimicrobial therapy. Image courtesy of Michelle V Lisgaris, MD.

CT scan of liver abscess reveals large anterior abscess involving left hepatic lobe. Abscess was successfully treated with percutaneous drainage and antimicrobial therapy. Image courtesy of Michelle V Lisgaris, MD.

Symptoms Percentage Signs Percentage
Abdominal pain89-100Normal findings38
Fever67-100Right-upper-quadrant tenderness41-72
Chills33-88Hepatomegaly51-92
Anorexia38-80Mass17-18
Weight loss25-68Jaundice23-43
Cough11-28Chest findings11-48
Pleuritic chest pain9-24