Clinical manifestations, diagnosis, treatment, and outcome of pyogenic liver abscess: a retrospective study

Abstract

Objective

The incidence of pyogenic liver abscess (PLA) continues to rise, yet atypical clinical symptoms result in considerable incidence of misdiagnosis. This study was conducted to identify potential warning indicators and summarize efficacious diagnostic and therapeutic approaches for potential clinical guidelines.

Methods

Hospitalized patients aged ≥18 years and diagnosed with PLA were included in this retrospective study. Data were collected from participant’s clinical records. Patients were grouped according to type 2 diabetes mellitus status and ultrasound-guided percutaneous drainage (USPD). Between-group differences were analysed with Student’s t-test.

Results

A total of 104 hospitalized patients were included, 33 of whom (31.73%) had type 2 diabetes. Procalcitonin levels were raised in all patients, suggesting potential effectiveness and sensitivity as a warning marker for PLA. Contrast-enhanced computed tomography was the most frequently used method (63.46% of cases) for diagnosing PLA. Klebsiella pneumoniae was the main pathogen found in patients with PLA in southeast China (isolated in 92.86% [26/28] of positive blood cultures and 90.70% [39/43] of positive abscess fluid cultures). Duration of hospital stay was shorter in patients who received USPD versus those who did not (17.91 ± 6.84 days versus 21.47 ± 9.82 days).

Conclusion

Types of PLA-susceptible patients, infection markers, highly sensitive imaging techniques and clinical treatment options were identified. These results may help with early accurate diagnosis of patients with PLA, avoiding treatment delay.

Introduction

Pyogenic liver abscess (PLA), referring to intrahepatic purulent lesions formed by pyogenic bacteria invading the liver, mostly caused by biliary tract and/or bloodstream infection, is a clinically serious infectious wasting disease. ¹ Patients with PLA frequently experience serious complications and mortality rates are often high. ² With improvements in imaging techniques, aetiological testing, antibiotics, and surgical procedures, significant progress has been made in the early-stage diagnosis and effective treatment of PLA. ³

Despite diagnostic and treatment improvements, the population of patients with PLA is increasing yearly and mortality rates remain as high as 8–31%.^4,5 This may be partially due to the increased incidence rate of diseases that induce PLA, such as hypertension, diabetes mellitus, biliary tract diseases, and tumours, in addition to the relatively high rate of missed diagnosis at the early disease stage, due to non-specific clinical manifestations (i.e., chills, fever, liver pain, hepatomegaly, and local tenderness) and delay between the initial application of antibiotics and aetiological testing results. ² The possible reasons for delayed diagnosis include the fact that: (a) chills, high fever, and fatigue, which are systemic symptoms, are not specific in themselves, and middle-aged and elderly patients may be insensitive to pain; and (b) abdominal pain, nausea and vomiting as the main clinical symptoms may easily be mistakenly attributed to gastrointestinal diseases. Therefore, identifying and characterising the population with high incidence of PLA, raising vigilance when patients seek medical advice, and promoting combined imaging and microbiology examinations will help to improve the diagnosis of patients with early-stage PLA and provide guidance for subsequent treatment.

In the present retrospective study, clinical characteristics, laboratory tests, aetiological examinations, antibiotic susceptibility tests, and treatments and outcomes were investigated in patients diagnosed with PLA who were admitted to the Affiliated Xiaoshan Hospital, Hangzhou Normal University, China, with the aim of identifying the susceptible patient population, defining important diagnostic indicators, improving the vigilance of empirical diagnosis, and summarizing the treatment plan. We believe this study may provide useful evidence and support in the empirical diagnosis and treatment of PLA, further preventing occurrence of the invasive syndrome and lowering the mortality rate of PLA.

Patients and methods

Study population

This retrospective study included consecutive patients who were admitted to the Affiliated Xiaoshan Hospital, Hangzhou Normal University, and diagnosed with PLA, between January 2017 and June 2022. This hospital, located in Southeast China (Hangzhou, Zhejiang Province), is a general hospital with excellence in healthcare, education, and research. PLA was diagnosed based on the following criteria: ⁶ (1) typical signs and symptoms, such as fever, chills, abdominal pain, and percussion tenderness over the hepatic region; (2) radiological examination (ultrasonography/ computed tomography [CT]/ magnetic resonance imaging [MRI]) indicating hepatic abscess; and (3) culture and specimen analyses of blood or pus showing positivity for a pathogenetic microorganism.

Patients who were aged <18 years, had incomplete clinical data due to death or discontinuation of treatment after diagnosis of PLA in the emergency room, or had liver abscesses caused by pathogens other than bacteria, such as fungi or Entamoeba histolytica, were excluded from the study.

This study was approved by the Medical Ethics Committee of Zhejiang Xiaoshan Hospital. Informed consent was waived by the Medical Ethics Committee due to the retrospective study design and data analysis. Confidentiality of patient information was confirmed, and patient data were de-identified for this study.

Data collection

Data were collected by reviewing the clinical records of all patients. Information on the patients’ demographic (sex and age), risk factors/comorbidities (type 2 diabetes mellitus, cancer, biliary tract disease, chronic hepatitis B, hypertension, and coronary diseases), clinical presentations, abscess site (right, left, or both hepatic lobes), maximal abscess diameter, laboratory values (including C-reactive protein [CRP], procalcitonin, and white blood cell [WBC] count), aetiological examinations (blood culture and pyoculture), imaging (ultrasonography, CT, or MRI), medical treatments, and treatment outcomes were collected and analysed.

The treatment outcome was evaluated within 4 weeks of hospital admission, and was classified as cured, clinically improved, treatment failure, or death, according to the following criteria: cured refers to the disappearance of clinical presentations, such as chills and fever, abdominal pain, weakness, nausea and vomiting, back pain, and the disappearance of abscess; clinically improved refers to improved clinical presentations, such as chills and fever, abdominal pain, weakness, nausea and vomiting, back pain, and images indicating that the abscess is at the absorption stage and shows shrinkage; while treatment failure refers to no-improvement in clinical presentations, such as chills and fever, abdominal pain, weakness, nausea and vomiting, back pain, and the abscess remains without evidence of shrinkage. All patients were followed-up for 12 months after discharge to understand their recovery.

Analysis of microorganisms and their drug sensitivity

Patients completed laboratory tests for indicators, such as routine blood parameters, CRP, albumin, transaminase, lactic acid, prothrombin time (PT) and international normalized ratio (INR), procalcitonin and blood culture within 48 h of admission, and completed abdominal ultrasound/CT/MRI examination within 1 week of admission. Patients who did not respond to initial treatment underwent ultrasound-guided percutaneous drainage (USPD) to drain the liver abscess. Pathogenic microorganisms in blood or abscess samples from patients with liver abscess were cultured and identified using a BD BACTEC FX400 automatic microbial blood culture system (Becton, Dickinson and Company; Franklin Lakes, NJ, USA) and the VITEK2 Compact automated microbial identification and antibiotic susceptibility testing instrument (bioMerieux; Marcy-l'Étoile, France), according to the manufacturers’ instructions. Bacterial drug sensitivity was determined by analysing the minimum inhibitory concentration using the identification and antibiotic susceptibility testing card (Vitek 2 Compact; bioMerieux). The selection of antibiotics and interpretation of drug sensitivity results was based on American Clinical and Laboratory Standards Institute recommendations. ⁷ Results were analysed using WHONET software, version 5.6 (www.whonet.org).

Statistical analyses

Data were statistically analysed using IBM SPSS software, version 24 (IBM Inc., Armonk, NY, USA). Categorical variables are presented as n (%) prevalence, and continuous data with normal distribution are presented as mean ± SD. Student’s t-test was used to evaluate differences in continuous variables between patients subgrouped according to type 2 diabetes mellitus status or whether or not they received USPD. A P value <0.05 was considered statistically significant in all analyses. All statistical methods were verified by statistics experts (HW and XX) at the Affiliated Xiaoshan Hospital, Hangzhou Normal University. The reporting of this study conforms to STROBE guidelines. ⁸

Results

Epidemiological summary

A total of 104 patients with PLA, including 67 (64.42%) males and 37 (35.58%) females, were included in this study (Table 1). The mean age of the male and female patients was 59.25 ± 15.90 (range, 18–85) years and 59.97 ± 11.22 (range, 23–91) years, respectively. Approximately half of the patients (46.15%) were aged between 60 and <80 years, and 37.5% were aged between 40 and <60 years. Fewer cases were recorded for the younger (aged <40 years [9.61%]) and older (aged ≥80 years [6.73%]) population.

Table 1.

Demographic, clinical, and treatment outcome data of patients with pyogenic liver abscess.

Characteristic	Total study population (n = 104)
Sex
Male	67 (64.42)
Female	37 (35.58)
Mean age, years
Male	59.25 ± 15.90
Female	59.97 ± 11.22
Age, years
18‒<40	10 (9.61)
40‒<60	39 (37.50)
60‒<80	48 (46.15)
≥80	7 (6.73)
Clinical presentation
Chills and fever	90 (86.54)
Abdominal pain	34 (32.69)
Weakness	9 (8.65)
Nausea and vomiting	5 (4.81)
Back pain	5 (4.81)
Comorbidity
Type 2 diabetes mellitus	33 (31.73)
Biliary disease	14 (13.46)
Malignancies	10 (9.61)
Hypertension/coronary  artery disease	9 (8.65)
Chronic hepatitis B	3 (2.88)
Inflammatory bowel disease	2 (1.92)
Acute gastroenteritis	1 (0.96)
No underlying conditions	32 (30.77)
Imaging test
Contrast-enhanced  computed tomography	66 (63.46)
Ultrasound	23 (22.12)
Contrast-enhanced  magnetic resonance imaging	9 (8.65)
Magnetic resonance imaging	3 (2.88)
Computed tomography	3 (2.88)
Abscess site
Right hepatic lobe	89 (85.58)
Left hepatic lobe	13 (12.50)
Both lobes	2 (1.92)
Maximal abscess size, cm	5.19 ± 2.35
≤3	14 (13.46)
>3‒5	40 (38.46)
>5‒10	44 (42.31)
>10	6 (5.77)
Complication
Pneumonitis	11 (10.58)
Pleural effusion	4 (3.85)
Septic shock	3 (2.88)
Lung abscess	1 (0.96)
Treatment outcome
Cured	17 (16.35)
Improved	84 (80.77)
Failure	3 (2.88)
Death	3 (2.88)

Data presented as n (%) prevalence or mean ± SD.

Clinical presentation

Baseline clinical characteristics are summarised in Table 1. The main clinical presentations were chills and fever (90/104 patients, 86.54%) and abdominal pain (34/104 patients, 32.69%). Weakness (nine of 104 patients, 8.65%), nausea and vomiting (five of 104 patients, 4.81%), and back pain (five of 104 patients, 4.81%) were less common clinical manifestations. The major PLA comorbidity was type 2 diabetes mellitus, observed in 33/104 patients (31.73%). Other comorbidities included biliary disease (14/104 patients, 13.46%), malignancies (10/104 patients, 9.61%), hypertension/coronary heart disease (nine of 104 patients, 8.65%), and chronic hepatitis B (three of 104 patients, 2.88%). Of note, 32 of the patients (30.77%) had no comorbidity. All patients completed imaging examinations of the liver and/or abdomen. To confirm the diagnosis of PLA, contrast-enhanced (CE)-CT (66/104 patients, 63.46%) and ultrasonography (23/104 patients, 22.12%) were more frequently used than CE-MRI (nine of 104 patients, 8.65%), MRI (three of 104 patients, 2.88%), and CT (three of 104 patients, 2.88%). Imaging results showed that most of the abscesses (85.58%) occurred in the right hepatic lobe (with more blood supply), and only 12.50% occurred in the left lobe, with 1.92% occurring in both lobes. The mean maximal abscess diameter was 5.19 ± 2.35 cm (with the maximal diameter of a single abscess ranging from 0.8 to 12.8 cm) and 38.46% and 42.31% fell in the range of >3–5 cm and >5–10 cm, respectively (Table 1). Representative CT and CE-MRI images from the same patient at admission and after treatment are shown in Figure 1.

Figure 1.

Representative images of the liver of a patient before and after treatment for pyogenic liver abscess, showing: (a) abdominal computed tomography (CT) at admission to the Emergency Intensive Care Unit in March 2022, displaying a maximal abscess diameter of 72.78 mm, with a CT value of 18 HU; (b) contrast-enhanced magnetic resonance images obtained after treatment in April 2022 indicating a maximal abscess diameter of 57.40 mm and CT value of 385 HU and (c) abdominal CT obtained in November 2022 displaying no obvious abscess in the liver.

Laboratory parameters

Among the 104 patients with PLA included in the study, mean levels of WBCs (normal range, 3.5–9.5 × 10⁹/L), CRP (normal range, 0–8 mg/L), alanine aminotransferase (normal range, 9–50 U/L), aspartate transaminase (normal range, 15–40 U/L), and lactic acid (normal range, 0.5–1.6 mmol/L) were elevated, while albumin level (normal range, 40–55 g/L) was decreased, compared with the normal population. Platelet count and PT/INR were observed to be within normal ranges. Patients with PLA showed increased procalcitonin levels (range, 1.07–55.18 µg/L) compared with the normal healthy population (normal range, 0.000–0.046 µg/L), and procalcitonin levels were significantly higher in patients with PLA and type 2 diabetes mellitus (mean, 17.05 ± 13.88 µg/L) than those without diabetes (mean, 9.54 ± 8.84 µg/L (P = 0.002). Patients with type 2 diabetes were also found to have significantly decreased albumin levels (mean, 31.63 ± 3.77 g/L) versus patients without diabetes (mean, 34.42 ± 4.32 g/L; P = 0.002; Table 2).

Table 2.

Laboratory test results in patients with pyogenic liver abscess with or without type 2 diabetes mellitus.

	Study group			Statistical analyses
Characteristic	Total(n = 104)	With diabetes(n = 33)	Without diabetes(n = 71)	F	t	Statistical significance a
WBC count, ×109/L	11.26 ± 5.03	11.09 ± 5.04	11.34 ± 5.06	0.531	–0.237	NS
CRP, mg/L	176.46 ± 83.37	191.02 ± 79.97	169.69 ± 84.61	0.132	1.217	NS
PCT, μg/L	12.07 ± 11.31	17.05 ± 13.88	9.54 ± 8.84	3.84	3.26	P = 0.002
Platelet count, ×109/L	192.93 ± 112.07	180.79 ± 84.50	198.58 ± 122.94	1.451	–0.752	NS
ALT, U/L	61.65 ± 56.05	55.41 ± 39.82	64.55 ± 62.21	2.002	–0.772	NS
AST, U/L	60.00 ± 48.24	69.70 ± 55.58	55.50 ± 44.13	3.40	1.403	NS
Albumin, g/L	33.54 ± 4.34	31.63 ± 3.77	34.42 ± 4.32	0.039	–3.193	P = 0.002
Lactic acid, mmol/L	2.20 ± 1.94	2.42 ± 2.09	2.08 ± 1.88	0.148	0.58	NS
PT/INR	1.12 ± 0.15	1.11 ± 0.15	1.12 ± 0.15	0.14	–0.484	NS
Hospital stay, days	18.55 ± 8.86	22.67 ± 9.28	16.63 ± 8.03	0.004	3.392	P = 0.001

Data presented as mean ± SD.

WBC, white blood cell; CRP, C-reactive protein; PCT, procalcitonin; ALT, alanine aminotransferase; AST, aspartate transaminase; PT, prothrombin time; INR, international normalized ratio.

^aPatients with diabetes versus patients without diabetes (Student’s t-test).

NS, no statistically significant between-group difference (P > 0.05).

Aetiological investigation

Defining the different bacterial pathogens that cause PLA remains challenging. Blood and abscess fluid samples were cultured to determine the causative pathogen in the studied cases (Table 3). A higher rate of positive cases was observed in cultured abscess fluid (93.48%) than in blood culture (35.00%). Klebsiella pneumoniae was the dominant cause of PLA in this study, accounting for 92.86% (26/28) of positive blood cultures and 90.70% (39/43) of positive abscess fluid cultures. Additionally, Escherichia coli was found in one case (1.25%), while E. coli and Aeromonas jandaei were found simultaneously in one case (1.25%) out of the 80 cases analysed by blood culture. Abscess fluid culture revealed E. coli in two of 43 positive cases (4.65%), Enterococcus faecalis in one of 43 (2.33%), and Staphylococcus aureus in one of 43 (2.33%). K. pneumoniae was found in both the blood and fluid cultures of 12 patients. Compared with gram-positive organisms (i.e., E. faecalis and S. aureus), gram-negative organisms, including K. pneumoniae and E. coli, appeared to be the dominant cause of PLA (Figure 2).

Table 3.

Results of pathogen testing in patients with pyogenic liver abscess.

Characteristic	Total study population(n = 104)
Blood culture	80
Positive cases	28 (35.0)
Klebsiella pneumoniae	26 (32.50)
Escherichia coli	1 (1.25)
Escherichia coli +   Aeromonas jandaei	1 (1.25)
Abscess fluid culture	46
Positive cases	43 (93.48)
Klebsiella pneumoniae	39 (84.78)
Escherichia coli	2 (4.35)
Enterococcus faecalis	1 (2.17)
Staphylococcus aureus	1 (2.17)

Data presented as n (%) prevalence.

Figure 2.

Pie chart showing percentages of different microorganisms identified by blood or fluid culture from 104 patients with pyogenic liver abscess.

Antibiotic sensitivity tests for the isolated microorganisms were also conducted. The 26 K. pneumoniae-positive cases in blood culture and 38 K. pneumoniae-positive cases in pyoculture were susceptible to third-generation cephalosporins, quinolones, aminoglycosides and negative in the extended-spectrum β-lactamase (ESBL) testing. One of the K. pneumoniae-positive cases in pyoculture was found to be carbapenem-resistant. K. pneumoniae was susceptible to ceftazidime and cycloavibactam, and was resistant to ertapenem.

Treatments and outcomes

All 104 patients received intravenous antibiotics after hospitalization. Initial antibiotic treatment choices, selected on an empirical basis, are listed in Table 4. Cefoperazone/sulbactam and imipenem/cilastatin were among the most commonly prescribed antibiotics, accounting for 44 and 25 cases, respectively. Piperacillin/tazobactam (11 cases [10.57%]), biapenem (nine cases [8.66%]), meropenem (four cases [3.85%]), cefoxitin (three cases [2.88%]), ceftizoxime (two cases [1.92%]), sulbenicillin (two cases [1.92%]), amoxicillin/clavulanic potassium (one case [0.96%]), moxifloxacin (one case [0.96%]), and ceftriaxone (one case [0.96%]) were also antibiotics of choice. A combination of ceftazidime/avibactam with tigecycline was selected as initial treatment for the patient with carbapenem-resistant K. pneumoniae. Third-generation cephalosporins, enzyme inhibitor antibiotics, and carbapenems were among the primary choices.

Table 4.

Antibiotic selection and corresponding number of patients in the initial and secondary phase of antibiotic treatment.

Initial treatment		Secondary treatment
Antibiotic	Number of patients, n	Antibiotic	Number of patients, n
Cefoperazone/sulbactam	44	Imipenem/cilastatin	6
		‒	‒
Imipenem/cilastatin	25	‒
Piperacillin/tazobactam	11	‒	‒
Biapenem	9	‒	‒
Meropenem	4	‒	‒
Cefoxitin	3	Imipenem/cilastatin	3
Ceftizoxime	2		2
Sulbenicillin	2		2
Amoxicillin/clavulanic potassium	1		1
Moxifloxacin	1	Cefoperazone/sulbactam	1
Ceftriaxone	1	‒	‒
Ceftazidime/avibactam+ tigecycline	1	‒	‒

For patients without improvement in clinical symptoms after initial treatment, the antibiotic type was adjusted according to drug susceptibility results from blood and/or abscess fluid cultures. Patients who were initially treated with cefoxitin, ceftizoxime, sulbenicillin, or amoxicillin/clavulanate potassium, and six of the patients initially treated with cefoperazone/sulbactam, were administered imipenem/cilastatin as the secondary antibiotic treatment; while moxifloxacin was replaced with cefoperazone/sulbactam in one case.

In patients who received abdominal ultrasound, the examination was completed within 1 week of admission. USPD was performed to drain the pus as soon as possible. A total of 58 patients (55.77%) received simple anti-infective therapy, and 46 patients (44.23%) underwent antibiotic treatment followed by USPD. Larger abscesses are known to be easier to puncture. In patients with a maximum abscess diameter ≤ 3 cm, a lower proportion underwent USPD (one of 14 patients [7.14%]) versus those with a maximum abscess diameter >5 cm (29/44 patients [65.91%] with a maximum abscess diameter >5–≤10 cm and five of six patients [83.33%] with a maximum abscess diameter >10 cm; Figure 3). The hospital stay of patients who underwent USPD was significantly shorter compared with those who did not undergo USPD (P = 0.04; Table 5).

Figure 3.

The number and proportion (%) of patients with pyogenic liver abscess who did or did not undergo ultrasound-guided percutaneous drainage (USPD), grouped according to maximal abscess diameter. Stars represent percentage of patients in each group who underwent USPD.

Table 5.

Length of hospital stay in patients who underwent ultrasound-guided percutaneous drainage (USPD) versus those who did not undergo USPD as part of treatment.

	Study group
Characteristic	USPD(n = 46)	Non-USPD(n = 58)	F	t	Statistical significance
Hospital stay, days	17.91 ± 6.84	21.47 ± 9.82	2.766	2.084	P = 0.04

Data presented as mean ± SD.

Among the study population, complications included pneumonitis (11/104 patients, 10.58%), pleural effusion (four of 104 patients, 3.85%), septic shock (three of 104 patients, 2.88%), and lung abscess (one of 104 patients, 0.96%). The mean length of hospital stay was 18.55 ± 8.86 days. Hospital stay was significantly longer in patients with type 2 diabetes versus those without diabetes (P = 0.001; Table 2). The treatment outcome was evaluated for each patient within 4 weeks of admission. A total of 17 cases (16.35%) were classified as cured, 84 cases (80.77%) were clinically improved, treatment was ineffective (failed) in three cases (2.88%), and three patients died (2.88%) within the 4-week timeframe. Data collected during follow-up over 12 months after hospital discharge showed that 17 of the cured patients had no recurrence within 12 months; 58 of the improved patients were cured within 3 months; 18 of the improved patients were cured within 6 months; and eight of the improved patients were cured within 8 months. All three patients for whom treatment was ineffective had died within 1 month.

Discussion

The present study population was predominantly male, with PLA onset occurring mostly in middle-aged and elderly patients, consistent with previously published reports.^9–11 In the present study, there were two cases of inflammatory bowel disease, one case of acute gastrointestinal inflammation, and two cases of colon cancer in 10 patients with malignant tumours. Biliary diseases, malignant tumours, and hypertension/coronary heart disease, may be risk factors for PLA, while fatigue, contaminated diet, and other intestinal and biliary infectious diseases may be factors that induce PLA. Because the liver has a dual blood supply from the portal vein and hepatic artery, and is connected to the intestinal lumen through the biliary tract, it may be susceptible to infection once there is a combination of biliary tract disease (as found in 14 patients [13.46%] in the present study) and cancer.^11,12 In patients with PLA, differences between those with or without diabetes mellitus has been studied previously,^13,14 and in the present study, type 2 diabetes mellitus was found to be a major PLA comorbidity. Patients with diabetes mellitus may have low immunity and poor ability to resist infection, and may more easily develop acute suppurative inflammation. In addition, high blood sugar level will inhibit the function of white blood cells, reducing their antibacterial activity, and facilitating the growth and reproduction of bacteria. Bacteria are more likely to enter the liver through the blood circulation or biliary tract, thus inducing the formation of PLA. Clinically, it is possible to dynamically monitor the level of glycosylated haemoglobin and actively control a patient’s blood sugar level, which may reduce the risk of infection.

The diagnosis of PLA requires a combination of clinical features, imaging results, and microbiological test results. As the incidence of PLA increases yearly, more and more cases show atypical clinical manifestations. Similar to previous reports,^15,16 the majority of onset symptoms in the present study included chills and fever (in 86.54% of cases), which was much more than the 34 cases (32.69%) showing pain in the abdomen. In addition, in nine of the present cases (8.65%), PLA was not initially considered a possibility due to the symptom of fatigue. Potential reasons for atypical clinical manifestations resulting in diagnosis difficulties include the fact that: (a) chills, high fever, and fatigue, which are systemic symptoms, are not specific in themselves, and middle-aged and elderly patients may be less sensitive to pain, and (b) those with abdominal pain, nausea and vomiting as the main clinical symptoms may easily be confused as having gastrointestinal diseases. Inflammation may not affect the liver envelope during the early stage of liver abscess formation and may not be associated with the typical symptoms of relatively specific liver pain, so typical symptoms are relatively rare. ¹⁷ Particular attention should be paid to patients exhibiting uncharacteristic clinical symptoms, such as those with fever, with or without chills, but without any specific abnormal symptoms.

High-sensitivity CRP is an inflammatory response marker synthesized by the liver. When a tissue is damaged, the CRP level may increase sharply within a few hours, and reach a peak within 2–3 days. Therefore, CRP is generally used as a supplementary marker in the early diagnosis of infection, but not as the main basis for diagnosis. ¹⁸ Elevated CRP levels (mean, 176.46 ± 83.37 mg/L) were observed in patients with PLA in the present study, but no statistically significant difference was observed between patients with or without diabetes. This may also suggest that there is no significant difference in infection-related increased CRP levels between different patient groups, so CRP may not be used to determine the severity of infection in different patient groups. Therefore, CRP displays low specificity as a marker of infection. ¹³

Procalcitonin, the precursor of human calcitonin, is a glycoprotein composed of 116 amino acids that is not released into the blood circulation under normal circumstances. Plasma procalcitonin levels in healthy individuals is very low (<0.1 µg/L), while plasma procalcitonin levels may be abnormally increased in patients with bacterial infection, under the stimulation of bacterial endotoxin and various inflammatory cytokines. The increase of procalcitonin during infection is positively correlated with the severity of infection, and is not influenced by the immunosuppressive state of the body. Moreover, the onset of procalcitonin stimulation is earlier than other inflammation cytokines, such as CRP. ¹⁹ As a result of its high specificity and sensitivity, procalcitonin has been widely used in clinical laboratory examinations of various infectious diseases. If procalcitonin content is higher than 0.5 µg/L, there is a risk of inducing sepsis. ²⁰ In the present study, patients with PLA showed increased procalcitonin levels (1.07–55.18 µg/L) compared with the normal range, and procalcitonin levels were significantly higher in patients with type 2 diabetes mellitus than those without diabetes (P = 0.002). The present results may indicate that patients with combined PLA and diabetes are more prone to sepsis. However, in our clinical experience, we have found that in patients with diabetic ketoacidosis combined with PLA, procalcitonin increase is related to serious dehydration, blood concentration and infection of the body, and procalcitonin drops sharply following active volume expansion and fluid replacement. The increased procalcitonin may possibly be related to infection and blood concentration. As procalcitonin, routine blood analysis, and CRP tests were not synchronized in some patients during data collection in the present retrospective analysis, it was impossible to dynamically trace and evaluate changes in related inflammatory factors as a function of time.

Diagnosis of early-stage liver abscesses by ultrasound alone is challenging. In the present study, CE-CT and ultrasonography confirmed 89 cases, accounting for 85.58% of the cohort. CE-CT and CE-MRI have been shown to have high sensitivity (up to 95%), and can detect liver abscesses with a diameter of 0.5 cm.^16,21 Images showed that abscesses were mostly located in the right lobe of the liver (85.58%) in the present study, and the maximal diameter of a single abscess was between 0.8 and 12.8 cm (mean, 5.19 ± 2.35 cm). This may be attributed to the larger size, shorter right hepatic duct, and more vigorous blood flow of the right hepatic lobe than the left lobe.^15,22

In the present study, the rate of bacteria-positive cases was much higher in abscess puncture fluid (93.48%) than that of blood culture (35%). Most patients had already used antibiotics before the blood culture, and most blood cultures were collected only once, which may explain the low positive rate in blood culture. Among patients with positive blood and abscess fluid cultures, K. pneumoniae was found to be the major pathogen of PLA, which is consistent with previous reports,^13–15 but differs from a European study, in which E. coli was reported to be the most commonly identified organism. ²² According to in vitro drug susceptibility tests, empirical use of third-generation cephalosporins and quinolone antibiotics may achieve satisfactory outcomes. However, with the aging population, the widespread use of antibiotics, the increased rate of underlying diseases, and the gradual increase of PLA infections by drug-resistant bacteria, the use of enzyme inhibitors or carbapenem antibiotics may quickly control the disease. Of note, the aetiology results from blood and abscess fluid cultures may also indicate drug resistance if antimicrobial therapy was received prior to culture. Overall, these results may shed light on the rational use of antibiotics for appropriate antibiotic treatment. ²⁰ Because the present study was retrospective, and there was no uniform selection of antibiotics for initial treatment, there was a diversity of antibiotics used for initial treatment; and due to the differences in microbial drug sensitivity and resistance in different regions, the results of this study have regional limitations.

Fifty-eight of the present patients (55.77%) received only anti-infective therapy, and 46 patients (44.23%) underwent USPD after antibiotic treatment. Duration of hospital stay was found to be significantly shorter in patients who underwent USPD than those who did not receive USPD. It is possible that USPD may rapidly reduce the patient's body temperature and relieve symptoms of sepsis, thereby accelerating the closure of the abscess cavity. ²³ In the present study, the USPD rate was found to increase from 7.14% to 83.33% as the size of the abscess increased from ≤3 cm to > 10 cm (Figure 3). If the diameter of the abscesses is small, there may be no liquefaction, ultrasound localization may be difficult, and puncture may easily cause trauma to normal liver tissue. If the diameter of the abscesses is large and liquefaction is complete, the amount of infected necrotic material is large, and ultrasound localization may be easy. Puncture and drainage may eliminate the infected necrotic material in a short time, which is conducive to aetiological diagnosis, abscess reduction, and healing of the lesion. In view of the above research, early puncture and drainage, where possible, in the treatment of PLA, may reduce clinical symptoms and shorten the clinical recovery time.

Treatment of PLA varies between studies and depends mainly on the condition of individual patients. In the present study, the mean length of hospital stay was 18.55 ± 8.86 days, the rate of cured and improved cases was 97.11%, and treatment was ineffective in three (2.88%) cases (where treatment outcome was evaluated within 4 weeks of admission). Follow-up over 12 months after discharge revealed that 17 of the cured patients did not experience recurrence within 12 months; 58 improved patients were cured within 3 months; 18 improved patients were cured within 6 months; and eight improved patients were cured within 8 months. The three patients for whom treatment was ineffective had died within 1 month. All three of these cases may have been attributed to underlying health conditions and low immunity: one patient had diabetes mellitus and spent prolonged periods in bed, while the other two cases had metastatic cancers.

The present research may be limited by certain factors. The study population comprised hospitalized patients diagnosed with liver abscess, and patients diagnosed with PLA in the emergency room who died or who stopped treatment and left the hospital voluntarily and had incomplete clinical data, were excluded. Therefore, the mortality rate reported here differs from that reported in previously published studies. The present study population was followed-up for 12 months. Due to the lack of continuous follow-up, no recurrent cases were found, so it is not possible to calculate the PLA recurrence rate.

Conclusion

In this study, middle-aged and elderly adults, particularly those with type 2 diabetes mellitus, underlying biliary tract disease, or cancer, were more likely to have PLA. Because of the atypical symptoms, close attention must be paid to missed diagnosis of PLA. Although metagenomic next-generation sequencing is useful for early screening, ²⁴ current low prevalence and high medical costs require clinicians to identify adequate risk markers for PLA. Through serological analysis, this study revealed the possibility of procalcitonin as a potential warning marker for PLA, especially in patients with diabetes. PLA may be diagnosed with high sensitivity using either CE-CT or CE-MRI after warning markers are indicated. The primary pathogen causing PLA was found to be K. pneumoniae, and the positive detection rate was higher in abscess fluid culture than blood culture. For patients with puncture indications, USPD should be encouraged as soon as possible. Together with early and rational selection of antibiotics for anti-infective treatment, USPD may improve clinical efficacy and shorten the hospitalization period.