Review Article The Evolving Nature of Hepatic Abscess: A Review Marianna G. Mavilia*1, Marco Molina2 and George Y. Wu3 1University of New England College of Osteopathic Medicine, Biddeford, ME, USA; 2Department of Radiology, UCONN Health, Farmington, CT, USA; 3Department of Medicine, Division of Gastroenterology-Hepatology, UCONN Health, Farmington, CT, USA Abstract in Taiwan.16 In the early 1900s, mortality was as high as 75%–80%,4 while today, mortality is markedly decreased, Hepatic abscess (HA) remains a serious and often difficult to ranging from 10%–40%.8 This is due to improvements in anti- diagnose problem. HAs can be divided into three main biotic therapy and interventional procedures for the treatment categories based on the underlying conditions: infectious, of HA.3,4,6 malignant, and iatrogenic. Infectious abscesses include those Although mortality is improved, it is still high, making early secondary to direct extension from local infection, systemic diagnosis of HA exceedingly important to the clinical outcome. bacteremia, and intra-abdominal infections that seed the HA can be difficult to diagnose, and the symptomatology is portal system. However, over the years, the etiologies and variable. Often, objective findings are nonspecific,16,17 and risks factors for HA have continued to evolve. Prompt recog- therefore, diagnosis relies largely on imaging.2 nition is important for instituting effective management and The aim of this review is to describe some of the changes in obtaining good outcomes. important risk factors, mechanisms, and patterns of develop- © 2016 The Second Affiliated Hospital of Chongqing Medical ment of HA and to review the current recommendations for University. Published by XIA & HE Publishing Inc. All rights the diagnosis and treatment of this condition. reserved. Risk Factors There are many risk factors associated with the development Introduction of HA and increased mortality from HA. These factors are detailed in Table 1. Risk factors predisposing patients to HA Hepatic abscess (HA) can be defined as an encapsulated range from diabetes mellitus (DM), cirrhosis, general collection of suppurative material within the liver paren- immune-compromised state, use of proton pump inhibitor 1,2 chyma, which may be infected by bacterial, fungal, and/ (PPI) medications, gender, and age. 2 or parasitic micro-organisms. Since the majority of HAs in DM is a predisposing factor for HA that is well documented 2,3 the Western world are infected with bacteria, pyogenic in the literature. 5,18,19 Studies have found DM as a concom- liver abscess will be the focus of this review. itant disease in 29.3%–44.3% of patients with HA.5,19 Diabetic In the early 1900s, the most common cause of HA was patients are also more likely to present with multiple 4 pylephlebitis secondary to appendicitis. In the late 1900s, abscesses.19 There are several pathophysiologic features of 4,5 biliary tract disease emerged as the most frequent culprit, DM that contribute to higher infection risk.18,20 For instance, 2,6,7,8 and it remains the most common cause of HA today. More hyperglycemia is known to alter neutrophil metabolism.21 Dia- recently, there has been an increase in the incidence of HA betics also have been shown to have impaired polymorphonu- arising in association with malignancies and their treatment, clear leukocyte (PMN) chemotaxis and phagocytosis,18,20 4,9 including HA from liver metastasis and as complications of which weakens their immune defense against infections and transarterial chemoembolization (TACE) or radiofrequency leaves them more susceptible to abscess formation. 10–14 ablation (RFA). Like diabetics, patients with liver cirrhosis have an 15 Although the frequency of HA varies by region, the overall increased risk of HA due to their immune-compromised incidence is fairly low, ranging from 2.3 cases per 100,000 state.7 Cirrhotics are 15.4 times more likely to develop HA 15 hospital admissions in North America to 275.4 per 100,000 than the general population.7,22 Other conditions and treatments may compromise the Keywords: Liver abscess; Liver neoplasms; Iatrogenic disease; Risk factors. immune system and render it inadequate to counteract Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, pathogens. These include various immunodeficiencies, che- aspartate aminotransferase; CEUS, contrast-enhanced ultrasound; CT, computed tomography; DM, diabetes mellitus; EBA, enterobiliary anastomosis; FDA, Food motherapy, solid malignancies, immunosuppression therapy 20 23 and Drug Administration; GGT, gamma glutamyl transpeptidase; HA, hepatic after organ transplant, as well as splenectomy, all of abscess; HCC, hepatocellular carcinoma; INR, international normalized ratio; IV, which have been associated with an increased risk of HA. intravenous; MRI, magnetic resonance imaging; PD, percutaneous drainage; PMN, The use of PPI medications has also been found to polymorphonuclear leukocyte; PO, oral, PPI, proton pump inhibitor; RFA, radio- 24 frequency ablation; SD, surgical drainage; TACE, transarterial chemoemboliza- increase the risk of HA formation. This is presumably tion; US, ultrasound; WBC, white blood cell count. because PPI medications increase the gastric pH, which Received: 18 January 2016; Revised: 25 February 2016; Accepted: 09 March 2016 24 q decreases the natural gastric defense against bacteria. In DOI: 10.14218/JCTH.2016.00004. a large case-control study, Wang et al. demonstrated a dose- *Correspondence to: Marianna G. Mavilia, University of New England College of Osteopathic Medicine, 11 Hills Beach Road, Biddeford, ME 04005, USA. Tel: response relationship between HA formation and dose of PPI 24 +1-617-435-1185, Fax: +1-860-679-6582, Email: [email protected] over a 90 day period. Although this was a large study, 158 Journal of Clinical and Translational Hepatology 2016 vol. 4 | 158–168 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Mavilia M.G. et al: Evolving nature of hepatic abscess Table 1. Risk factors for development of hepatic abscess (HA) and were conducted in the same region and used very similar increased mortality from HA sample sizes, the difference in findings could be explained Increased risk of Increased mortality by the inclusion criteria. Chen et al. included only primary developing HA from HA HA, whereas Lee et al. did not specify the diagnosis as primary or secondary. Diabetes mellitus*5,8,19 Malignancy16 The theme of immune compromise is also seen in the Liver cirrhosis*22 Diabetes mellitus*5,16 mortality rates for HA. Mortality rates for HA in patients with *22 associated malignancy was reported to be double that of Immune-compromised Liver cirrhosis 26 20 cancer-free patients. As reported by Lin et al., patients with state hepatocellular carcinoma (HCC) and HA had a higher 60-day Use of PPI24 Male gender*16 mortality rate compared to those with HCC only.15 Addition- Advanced age19 Multiorgan failure16 ally, cirrhosis was associated with a 4-fold increase in the risk 22 *16 5 of death from HA. Mortality was also reported to increase Male gender Sepsis 4 when HA contained mixed organisms or fungal infection. Infection with mixed organisms4 Categorization HA rupture16 Abscess size > 5 cm5 For the purposes of this review, we have divided HA into three Respiratory distress16 subgroups based on category: infectious, malignant, and iatrogenic. There are some areas of overlap between catego- Hypotension16 ries, as depicted in Figure 1. Jaundice16 16 Extrahepatic involvement Infectious Abscess *Diabetes mellitus, liver cirrhosis and male gender are risk factors for both development and increased mortality of HA. Pathogens may gain access to the liver through contiguous spread from infection of neighboring tissue, from blunt or penetrating trauma to the abdomen,9,27 and through hema- encompassing 10 years of data, it was conducted exclusively togenous spread (Fig. 2).2 The latter most commonly occurs in Taiwan, where the incidence of HA in general is high. Addi- due to systemic bacteremia or in intra-abdominal infections. tionally, control subjects were not matched for comorbidities However, bacteremia is only detectable in 43% of HAs,9 or indication for PPI use. Both of these factors may have had making diagnosis of HA in this instance increasingly difficult. some influence on their findings. In cases of intra-abdominal infection, including appendicitis Most cases of HA present at advanced age. One study 19 and diverticulitis, bacteria can seed the portal vessels, reported a mean age > 57 years. This finding suggests that causing pylephlebitis and portal pyemia, ultimately leading to older individuals are more susceptible to bacterial infection 6,7 21 HA formation. A recent cohort study of 54,147 patients and thus abscess formation. However, more research is with diverticular disease and 216,588 matched controls needed to clarify the mechanism of this association. found the incidence of HA to be 2.44-fold higher in those In a 10-year audit of experience with HA from 1989 to with diverticular disease compared to controls.28 This study 1999, Lee et al. found the ratio of males to females presenting included patients with both diverticulosis and diverticulitis.28 5 17 with HA was about 2 to 1. This was confirmed by Pang et al. Of them, 10%–25% had