Pyogenic Liver Abscesses Caused by Acute Appendicitis: Frequency and Diagnostic and Therapeutic Recommendations

Abstract

Background:

Pyogenic liver abscesses (PLA) are caused by biliary diseases or hematogenous spreading of mostly intra-abdominal infections. Liver abscesses resulted in hematogenous spreading of infections via the portal vein, such as abscesses caused by acute appendicitis. Pyogenic liver abscesses associated with appendicitis have rarely been described in the literature, especially in adults. The standard therapeutic procedures for liver abscesses are broad-spectrum antibiotic therapy and percutaneous drainage. Surgery for liver abscesses is required in cases of unsuccessful processes.

Patients and Methods:

A retrospective analysis of patients with liver abscesses between January 2005 and June 2013 was performed. Parameters investigated included demographics, etiologies of abscesses, treatment modalities, and germ spectrum including antibiotic profile. Five cases of PLA caused by appendicitis were reviewed in detail.

Results:

During the study period, 49 patients with PLA and 1,986 patients with acute appendicitis were treated in our hospital. Twenty-one patients with PLA were treated with antibiotic agents and computed tomography (CT)-guided drainage. Liver resections were necessary in 29 of the patients with PLA. In five patients with PLA, abscesses were caused by an acute appendicitis (9.4% of all PLA, 0.25% of all appendicitis operations). Diagnosis of appendicitis as cause of PLA was made during surgery for liver resections in three patients. Previous imaging was not clear in all cases of PLA caused by appendicitis. The most common pre-operative symptoms in patients with PLA caused by appendicitis were fever and right upper quadrant tenderness.

Discussion:

Pyogenic liver abscesses caused by acute appendicitis are rare. In the study period of eight and one-half years nearly 2,000 cases of acute appendicitis were treated and five of these patients developed liver abscesses (0.25%). Pyogenic liver abscesses should be considered in patients with unusual high infectious parameters, septic symptoms, and detection of unknown liver lesions.

Pyogenic liver abscesses (PLA) are caused by biliary tract diseases, hematogenous spread of infections via the portal vein or hepatic artery, cryptogeneous, direct extension of subphrenic abscess or cholecystitis, or by penetrating trauma [1 –4]. Patients with PLA typically present with fever, chills, right upper quadrant pain, nausea, diarrhea, and anorexia [1]. Risk factors for PLA are immunosuppressive diseases such as diabetes mellitus, human immunodeficiency virus (HIV), or post-transplantation immunosuppression as well as hepatobiliary or pancreatic diseases and trauma [1,5]. Spectrum of pathogenic germs consists mainly of enteric bacteria such as Klebsiella spp., Escherichia coli, or Enterococcus spp. [4,6,7].

Basic diagnostic steps are laboratory and imaging studies such as ultrasonography and computed tomography (CT) [1,4]. Magnetic resonance imaging (MRI) can help to differentiate between abscesses and malignancies [7,8]. Ultrasonography with contrast media could be used to examine the vascularization of the liver processes to differentiate etiology of the liver masses [5].

Abscesses of the right lobe of the liver occur more often than in the left lobe, but PLA can also occur in both lobes (approximately 35% of the abscesses) [1,3]. The literature indicates a rate of nearly 30% of positive blood or abscess cultures. The current gold standard treatment is a combination of broad-spectrum antibiotic therapy and CT- or ultrasound-guided percutaneous drainage [1,4,8]. Antibiotic therapy must be continued until symptoms and radiologic findings of the abscess have resolved [1,5]. Liver resection as surgical treatment for PLA is indicated in critically ill patients and patients who do not response to antimicrobial therapy with or without drainages of the PLA [1,5,9].

Pyogenic live abscesses are rare complications of acute appendicitis described with an incidence of 0.03% in literature for pediatric surgery [2,10]. Case reports of appendicitis-associated PLA are mainly published in the pediatric literature [2]. We present a case series of five adult patients with PLA caused by acute appendicitis.

Patients and Methods

We present a retrospective analysis of adult patients (≥18 years old) treated with surgical and interventional therapy for PLA between January 2005 and June 2013. Case reports of patients with PLA caused by acute appendicitis were evaluated. Patient's demographics, comorbidities, primary imaging and results, primary laboratory findings, applied therapy, and microbiologic results were analyzed. Comparison of collected data with data of all urgent appendectomies at the same period was done. Data was analyzed with GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA). Means are given with range.

Results

In the study period, 49 patients with PLA were treated; there were 55 total interventions. Antibiotic therapy was established in all patients. Interventional treatment with CT-guided percutaneous drainage was primarily performed in 25 patients (mean age 64 years; range, 21–88 years; male to female ratio, 16:9). In four cases secondary surgical resections were necessary. Primary surgery was performed in 28 patients (mean age, 57 years; range, 18–81 years; male to female ratio, 20:8).

Etiologies and localizations of PLA, and therapeutic approaches are provided in Table 1. Pyogenic liver abscesses were more frequently located in the right lobe of the liver (n = 36; 67%), in the left lobe in 15 cases (26%), and in four cases bilateral localization of the PLAs was detected (7%). Pyogenic liver abscesses caused by hematogenous spreading infections of the lower gastrointestinal tract were diagnosed in 18.37% (n = 9); half were caused by acute appendicitis (n = 5). The other PLAs were caused by complicated diverticulitis (n = 4). Etiology of PLAs was detected in all patients with surgical treatment. In patients with radiological drainage placement (n = 25) etiology was unclear in six cases (24%).

Table 1.

Underlying Diseases of Pyogenic Liver Abscesses and Numbers of Patients Treated by Surgery or Interventional Drainage

Etiology of PLA	Surgery	Drainage	Total number	Total %
Tumor	5	2	7	13
Gallbladder	4	2	6	11
Trauma	1	0	1	2
Other pylephlebitic	4	2	6	11
Appendicitis	5	0	5	9
Biliary infection	3	4	7	13
Complication after hepatic interventions	7	10	17	31
Unknown	0	6	6	11

PLA = pyogenic live abscesses.

Microbiologic testing resulted in a wide range of bacterial findings. Most frequent findings were Streptococcus spp. (18%), Escherichia coli, and Enterococcus spp. (each 15%) and Fusobacteria spp., Lactobacillus spp., and Staphylococcus spp. (each 9%).

In the study period, 1,986 appendectomies were performed. Pyogenic liver abscesses were found in five patients with appendectomies (0.25%). Demographics, clinical symptoms, and blood test findings of these five patients are provided in Table 2. Relevant comorbidities and named risk factors were not described in surgery reports or patient files.

Table 2.

Analysis of Five Patients with Pyogenic Liver Abscesses Caused by Acute Appendicitis with Demographics, Clinical Symptoms, Clinical Process, and Results of Blood Tests by First Examination

Patient no.	Gender	Age (y)	Initial symptoms	Period of clinical symptoms	Diagnosis of appendicitis	Count of WBC/mcL	CRP mg/dL
1	Male	18	Fever, pain in the upper abdomen	10 d	Intra-operative finding	25,550	32
2	Female	55	Pain in the upper abdomen, worsening of general condition	45 d	Repeated CT scan	17,400	16
3	Male	32	Worsening of general condition, fever, sepsis	12 d	Intra-operative finding	23,530	24
4	Male	65	Fever, pain in the upper abdomen	28 d	Intra-operative finding	16,810	31
5	Male	46	Signs of appendicitis	3 d	Primary CT	20,210	23

WBC = white blood cell count; CRP = C-reactive protein; CT = computed tomography.

Computed tomography scans were performed prior to surgery in all cases of liver resections for PLA. In patients 1, 3, and 4 appendicitis was diagnosed during surgery for the PLA. Patient 2 was referred to our center from another hospital after diagnosis of PLA of unknown origin. In this case, in the repeat CT scan for percutaneous drainage, acute appendicitis was diagnosed. Patient 5 presented with the typical signs of appendicitis. A solitary liver mass was detected by point-of-care ultrasound. The CT of patient 5 is shown in Figure 1. Magnetic resonance imaging after appendectomy identified lesions as abscesses. Figure 2 shows the hemihepatectomy preparation of patient 1.

FIG. 1.

Intra-operative finding of a huge (*) and two smaller (#) encapsulated liver abscesses in the right lobe after hemihepatectomy.

FIG. 2.

Computed tomographic scan of patient 5 with simultaneous findings of acute appendicitis (#) and liver abscess (*).

Surgery with liver resection and simultaneous appendectomy was performed in four patients with pylephlebitic liver abscesses caused by appendicitis. In patient 5 a two-step procedure with a delay of 10 days between laparoscopic appendectomy and right hemihepatectomy was performed. Microbiologic findings in patients with PLA associated with appendicitis were Fusobacteriae (n = 1) and Streptococcae (n = 1); microbiological testing of the other patients had no results.

Length of hospital stay in patients with PLA caused by appendicitis was 10.3 days (range, 6–18 days). There were no documented recurrences of PLA. Follow-up was done successfully in four of five patients after a median of 22 months. Patients who were contacted were all well; one patient developed an incisional hernia.

Discussion

Pyogenic liver abscesses are rare. Pyogenic liver abscesses are seen in approximately 2.6 per 100,000 cases in North America [3]. In the article by Chen et al. [11], 17% of all patients with PLA were critically ill and required intensive care. The authors found a mortality rate of 28% in patients with PLA.

Imaging by ultrasound and CT of the abdomen are the gold standard diagnostic modalities for liver abscess [1,8]. Currently the main treatment of PLA is a combination of targeted antibiotic therapy and ultrasound- or CT-guided percutaneous drainage [1,6]. Drainage with aspiration or placement of drainage tubes is the gold standard in treatment of PLA. Indications for surgery include abscess rupture, uncorrected primary pathology, incomplete percutaneous drainage, inadequate clinical response after four to seven days of percutaneous drainage, and multiloculated abscesses [1,5]. Mezhir et al. [8] reported the association of failure of percutaneous drainage with the presence of yeast and communication with an untreated obstructed biliary tree.

The treatment of PLA should be determined by a multidisciplinary team involving surgery, interventional radiology, and infectious disease specialists. Early broad-spectrum antibiotic therapy should be started immediately [1,5]. In the literature the most common pathogens identified from abscess cultures consistently are Enterobactericea (gram-negative) namely Escherichia coli and Klebsiella spp. [1,5]; Streptococcus spp. (gram-positive) was most common, Escherichia coli was the second most common pathogen in our analysis. Primary treatment of liver abscesses with broad-spectrum antibiotic agents with an effect on gram-positive germs are required [1,3].

Drainage techniques may vary depending on surgical expertise and availability of interventional radiology [4,5,8]. Surgical treatment was performed more often in our analysis than in prior publications. The etiology of PLA was detected and well treated in all surgical-treated patients with PLAs. In six patients with PLA treated with radiologic placed drains causes of PLA remain unclarified. We hypothesize that appendicitis could be responsible for more than just these five cases, because in three of five patients, acute appendicitis was not found in the primary imaging or in the imaging for interventional drainage placement.

In the study period, 1,986 patients with an acute appendicitis were treated at our hospital. Pyogenic liver abscesses were detected in five patients with appendicitis (0.25%). In the pediatric surgery literature association of PLA and acute appendicitis is described in up to 0.03% [2,10]. Thus, we found a 10 times higher frequency in adults.

Pyogenic liver abscesses have increased morbidity and mortality [11]. In cases of PLA caused by hematogenous spreading of infections of the lower gastrointestinal tract (diverticulitis, appendicitis, or colitis) and detected origins, immediate causative treatment should be established. We analyzed 53 patients with liver abscesses. The most common causes of PLA were complications after liver surgery or interventions such as radiofrequency ablation or transarterial chemoembolization. Twenty percent of PLA were caused by hematogenous spreading of infections from the lower gastrointestinal tract and approximately half of them by appendicitis.

Determination of the etiology of PLA pre-operatively was not clear. In patients with PLA caused by appendicitis, all had abdominal pain and septic constellation with hypotension, tachycardia, and fever. Typical signs of appendicitis were absent in four of five patients. Only in patient 5 were clinical signs of acute appendicitis present with abdominal pain in the right lower abdomen. Other patients presented unspecific symptoms caused by the liver abscess, not by appendicitis.

Primary imaging by ultrasonography and CT scan was done in all patients with PLA caused by appendicitis. These imaging techniques are sensitive for the detection of hepatic abscess [1,3,6]. The diagnosis of PLA caused by an acute appendicitis was not found in primary imaging or by clinical symptoms. In two cases an MRI of the upper abdomen was performed because a liver malignancy was suspected in the CT images. The role of contrast-enhanced ultrasonography in patients with PLA could not be examined because we did not use the technique during the study period. Diabetes mellitus, immunosuppressive therapy after solid organ transplantation, or trauma are cited as risk factors for PLA [4,5]. None of these risk factors were found in the patients with PLA caused by appendicitis.

Although this study has limitations, namely the retrospective analysis and small patient number of patients with PLA caused by appendicitis, we nevertheless recommend a diagnostic algorithm (Fig. 3) to determine these patients.

FIG. 3.

Algorithm of clinical symptoms, radiological and laboratory findings in patients with possible PLA caused by acute appendicitis. CT = computed tomography; MRI = magnetic resonance imaging.

Conclusion

Pyogenic liver abscesses caused by acute appendicitis are rare. In 1,986 patients treated for acute appendicitis only five patients were diagnoses with associated PLA (0.25%). However, acute appendicitis caused PLA in 11% of all patients treated in the same period. Previous imaging was not clear in all patients with PLA associated with acute appendicitis. Typically risk factors for PLA were not found in patients with PLAs caused by appendicitis. We recommend that in patients with unknown liver masses, symptoms of sepsis, and high infectious parameters PLA associated with acute appendicitis be considered.

Footnotes

Funding Information

No funding was received.

Author Disclosure Statement

The authors have nothing to disclose.

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