TO THE EDITOR
Liver abscess (LA) is defined as a pus-filled mass in the liver caused by pyogenic, amoebic or, rarely, fungal pathogens[1]. Pathogen etiology varies by geographic location. In developed countries, pyogenic LA (PLA) comprises three-fifths of all cases, whereas amoebic LA (ALA) comprises two-thirds of total LA cases in developing countries[2,3]. Hepatic cystic echinococcosis (CE) is the most frequent localized chronic parasitic disease. It is caused by the ingestion of infective Echinococcus granulosus taeniid tapeworm eggs and occurs worldwide[4,5]. While the Pan American Health Organization publishes biennial epidemiological reports on CE as part of its elimination policy, data from Africa, Asia and Eastern Europe are limited. In 2021, data on echinococcosis were only available from the Americas and European regions: 2942 cases were reported from 22 countries. Many endemic countries still need to collect baseline data to accurately calculate the incidence of the disease[6]. LA incidence rates in Europe and North America range from 1 per 100000 people/year to 7 per 100000 people/year. PLA accounts for more than 80% of all LA cases[7]. Recently, the etiologies of PLA have shifted from intra-abdominal infections such as acute appendicitis and trauma to biliary tract pathologies[8]. These above mentioned findings are consistent with the results recently reported by Pillay et al[9]. In fact, in their two tertiary South African hospitals, PLA represented the majority (74.77%) of LA cases. Furthermore, Pillay and collaborators[9] reported that only 16.22% of their cases were amoebic, while the percentage of hydatid liver cyst (HLC) was 9.01%. As recently observed in Western countries, biliary tract disease (either benign or malignant) plays an important role in PLA etiology in South African patients. In the report by Pillay et al[9], organisms were cultured from blood in only 17.58% of patients with PLAs, whereas the abscess cultures were positive in 56.6% of cases. These results are consistent with our previous studies[10]. There are many differences between the causative pathogens in European and South African cases. As expected, Klebsiella, Escherichia coli and Streptococci were the most cultured organisms in the two tertiary South Africa hospitals, and 16% of cultures were polymicrobial. In Western cases, PLA was most commonly associated with Escherichia coli and other bacteria that are components of gastrointestinal flora. Over the last 20 years, Klebsiella pneumoniae has emerged as the principal pathogen in 50% to 88% of PLA cases in Asia, and its frequency increased in PLA cases in Europe, South Africa, and the United States[8]. Some related hypervirulent Klebsiella pneumoniae lineages (hvKp)[11] can lead to hard monomicrobial cryptogenic PLA and metastatic infections, such as endophtalmitis, bacteremia and brain abscess[12]. Cases of PLA due to hvKp infections in Europe are sporadic, and the first Italian case was described by De Francesco et al[12]. Although hvKp strains are emerging pathogens in Western countries, they still represent a minor contributor to LA etiology there; however, they have recently shown a marked increase in incidence in both Asia and Western countries[13]. In the West, up to 55% of PLA cases have unknown causes, in part because the patients do not exhibit any clear risk factors[8]. Pillay et al[9] reported that in their cases, the most common comorbidity was human immunodeficiency virus infection. In cases reported in Europe, diabetes mellitus has a strong association with PLA, especially among diabetic patients with poor blood sugar control[8].
PYOGENIC LA TREATMENT
For more than two decades, the gold standard treatment for PLA has been percutaneous drainage (PD) with intravenous broad-spectrum antibiotics that have activity against aerobic and anaerobic enteric bacteria[14]. In fact, the use of antibiotics alone is not sufficient to achieve therapeutic success in most patients with PLA, and additional interventional percutaneous procedures, such as percutaneous needle or catheter drainage, are necessary. It is best to perform the interventional percutaneous procedures as soon as possible to avoid major complications[13]. Losie et al[15] reported 221 PLA cases in Canada and found that the 30-day mortality dramatically increased when drainage was not performed. The question remains as to how to choose the optimal procedure that achieves the best therapeutic success with shorter hospital stays and the fewest procedure related complications. In a systematic review and meta-analysis published in 2015, the outcomes of percutaneous needle aspiration (PNA) among successfully treated patients were comparable to those of percutaneous catheter drainage[16]. In contrast, a recent meta-analysis concluded that catheter drainage was superior to needle aspiration in terms of treatment success and duration of antibiotic therapy, especially for large PLA[17]. In our own multi-year experience, PNA under ultrasound (US) guidance obtains excellent results in term of success rate and complication rates[10]. In a previous study, we treated 125 patients with 147 PLAs (mean diameter: 6.8 cm; range: 3-16 cm) using US-guided PNA and antibiotic therapy. Cure, as defined by normalization of clinical and laboratory parameters and resolution of hepatic lesions with reconstitution of liver parenchyma, was achieved in 113 patients (98.3%). Only two patients with large PLAs required surgery and in one of those, a false positive diagnosis of malignant tumor had been made. In the remaining eight patients, abscesses were evacuated in one session. There were no complications or deaths[10]. Since 1991, we still perform a single needle aspiration in a single session on an outpatient basis for stable patients. Such interventional approaches using US-guided PNA is also feasible for multiple PLAs, as multiple catheters cannot be used. However, PNA can be used to aspirate multiple abscesses in a single session without removing the needle from the liver[18]. In the United States, PD of multiple LAs demonstrated high safety and efficacy independently of abscess complexity and/or multiplicity[19]. Taken together, it is evident that US is the first and most rapid, non-invasive tool to diagnose PLA or ALA. Based on our clinical experience in the field of liver infectious disease and interventional US (which even more so can be exported to countries with scarce resources), once a pus-filled mass is observed by US [on the basis of patient history (fever, abdominal pain, travel abroad) and clinical examination], an immediate US abdominal scan should be performed followed by US-guided needle puncture and aspiration. Such an interventional approach can confirm the US-based diagnosis of an abscess and can help inform the nature of the abscess. In fact, the aspiration of yellow or green frank pus is consistent with PLA, while the aspiration of chocolate or anchovy material is indicative of an ALA. The caliber of the needle used for puncture and aspiration is dependent on the volume of the pus-filled mass as observed via US. Once the needle is inserted into the abscess, all fluid should be aspirated to reduce the abscess cavity as much as possible. Pus culture in the case of PLA or search and serology for Entamoeba hystolitica can then be performed. The patient should be treated immediately with broad spectrum antibiotics or metronidazole. Generally, aspiration of the abscess (either pyogenic or amoebic) results in a rapid improvement in clinical conditions and fever[20]. The introduction of point of care US into clinical practice has expanded the role of abdominal US in diagnosis. Point of care US has played a pivotal role in LA at both small and large hospitals, as it can aid in the rapid diagnosis and management of liver abnormalities, likely contributing to favorable outcomes[21]. If and when available, contrast-enhanced US has shown to have more clinical utility in treating PLA[22].
AMOEBIC LA
Amoebiasis is an extremely important public health problem in many tropical and subtropical regions. In India, the prevalence of Entamoeba hystolitica infection is very high, estimated at millions of cases. The World Health Organization (WHO) estimates that amoebiasis is the third cause of death after parasitic diseases such as malaria and schistosomiasis[6]. In Western non-endemic regions, amoebiasis is generally considered uncommon, except for the colonization with non-pathogenic amoeba species[23,24]. However, its incidence in developed European countries has significantly increased in recent decades due to travel and immigration of individuals from highly endemic areas. Our experience in US diagnosis and treatment of ALA began in 1979, and in addition to travelers from high risk regions such as Mexico, we have also observed some native cases (Campania, Italy)[25]. Up to 2007, 56 consecutive patients with 68 amoebic LAs were diagnosed at D. Cotugno Hospital for Infectious Disease in Naples, Italy based on aspirated fluid appearance and serology (indirect hemagglutination assay, enzyme-linked immunosorbent assay). All patients were treated with metronidazole and US-guided percutaneous puncture and aspiration. No patient had more than two US-guided puncture aspirations. Until the hospitalization of the last two patients in our series, all patients had recovered[25]. The last two patients were both male human immunodeficiency virus-negative immigrants. They were treated by PD, but their clinical conditions quickly worsened and neurological symptoms occurred. Computed tomography revealed brain abscesses in both patients, and they died within 3 days. This unfavorable outcome is a rare example of failure of percutaneous therapy in ALA. Death is possible even in non-endemic areas such as Italy[25].
HLC
In the report by Pillay et al[9], most HLCs were greater than 10 cm in diameter and the patients had been referred to their tertiary hospitals for surgery. Only a few patients underwent PD such as percutaneous aspiration of cystic fluid, injection of a scolicidal agent (95% sterile ethanol or 20%-30% hypertonic saline) and reaspiration (PAIR). In their study, Pillay et al[9] did not report the types of HLC they surgically treated (i.e. Gharbi et al’s study[26] or WHO classification[27]). The WHO classification is now widely used and is based on the correlation between US of HLCs and their stage of viability: pure liquid content (viable cyst), transitional stage, solid appearance (not viable cyst) or calcified cyst (not viable cyst). There are no available data on the viability of the surgically treated HLCs. However, the large size of the cysts suggests they were non-viable, in which case surgery would not have proven useful. Although liver cystic hydatidosis is considered benign and many patients are asymptomatic for years, the associated complications can be severe and life-threatening. Therefore, treatment is recommended for all viable and active cysts[28,29]. In recent years, PAIR has shown excellent results in treating HLC[30], and many studies have compared PAIR to albendazole alone or surgery. Khuroo et al[31] performed two trials. In the first trial, they compared PAIR plus albendazole vs albendazole alone and found that PAIR plus albendazole was superior to albendazole alone. In the second trial, they compared PAIR to surgery. While the efficacy was similar between the approaches, there were fewer complications and shorter hospital stays for PAIR[32]. In a review by Smego and Sebanego[33], PAIR had greater clinical efficacy (i.e. a higher incidence of cure), lower rates of major and minor complications, mortality, and disease recurrence, and shorter hospitalization stays compared to surgically treated patients. A meta-analysis by the Cochrane Collaboration recognized that PAIR is a promising technique that should be evaluated in future randomized clinical trials. However, their meta-analysis only evaluated results from PAIR with or without albendazole[34]. Sokouti et al[35] compared PAIR with laparoscopic surgery and found promising trends suggesting that PAIR was superior in treating liver hydatid cysts compared to laparoscopic procedures. Those investigators concluded that the PAIR procedure is preferred over laparoscopy due to its higher cure rate and lower complication and mortality rates. In 1992, we presented a modified PAIR technique termed double percutaneous aspiration and injection (D-PAI), which consisted of US-guided percutaneous needle puncture of the cyst, aspiration of cystic fluid, and injection of 95% sterile ethanol without re-aspiration. We treated 203 patients with 290 HLCs and followed them for up to 21 years[4]. To our knowledge, this is the only percutaneous technique that achieved US-guided complete loss of treated cysts in 64.85% of the cases and reduction in volume with solidification in 19.7% of cases. The parasitological cure rate was approximately 100%. The hospital stay ranged 1-3 days. Smaller cysts (< 5 cm) healed faster than larger cysts (P < 0.001). We concluded that D-PAI is a safe and effective option in percutaneous treatment of viable HLC. This is a very simple and inexpensive procedure that can be applied everywhere, which is particularly important for developing countries[4]. Our results have been recently confirmed in a randomized clinical trial that compared PAIR with surgery. Shera et al[36] found that D-PAI achieves results comparable to surgery, but with minimal invasiveness and morbidity and decreased hospital stays.
CONCLUSION
In conclusion, although LA and HLC are rare and neglected entities, respectively, they still represent still a potent challenge for diagnosis and treatment, even in European countries. Abdominal US can be the first tool in diagnosis, and US-guided interventional procedures can be utilized for both diagnosis and treatment, especially for LA. Percutaneous US-guided interventional needle aspiration or injection techniques are safe and very inexpensive procedures, which make them extremely useful approaches for developing countries.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Italy
Peer-review report’s classification
Scientific Quality: Grade B, Grade C, Grade C, Grade C
Novelty: Grade B, Grade B, Grade B, Grade C
Creativity or Innovation: Grade B, Grade B, Grade C, Grade C
Scientific Significance: Grade B, Grade B, Grade B, Grade B
P-Reviewer: Aydemir S; Carbone F; Kudu E S-Editor: Bai Y L-Editor: A P-Editor: Zhang XD
