Liver Abscess: Challenges in Diagnosis and Management in Low-Resource Settings

Liver abscesses can be divided into 2 categories: amoebic liver abscess (AHA) and pyogenic liver abscess (AHP). The pathogenesis of HA is different from the pathogenesis of AHP. In AHA, Entamoeba histolytica induces hepatic apoptosis, which is followed by suppurative infection of the liver parenchyma. Confirmatory diagnosis is important, although difficult in resource-poor settings, as it leads to treatment.

AHPs have a global distribution, although the incidence varies significantly between different countries, from more than 900 cases in a 10-year period in Asia, such as Taiwan, Singapore and southern Korea, to 23 cases in the same time period in other Asian regions. In the US, the incidence of AHP is 2.3/100,000 population, predominantly older men. Diabetes and cancer are considered risk factors for its development.

The most common pathogens isolated in this environment were Streptococcus milleri followed by Klebsiella pneumoniae . This differs from South Korea and Taiwan, where K. pneumoniae is the most commonly found pathogen.

Entamoeba histolytica is a protozoan that causes amoebiasis (gastrointestinal infection) and is mostly a common cause of intestinal parasite infection in travelers returning from affected regions. Entamoeba histolytica is distributed globally with higher infection rates in low- and middle-income countries compared to higher-income countries.

On the other hand, in higher-income countries, a significant proportion of cases are usually imported while non-imported cases usually affect immunosuppressed patients. The infection is associated with poor living conditions and contamination of drinking water. The high rates of E. histolitica abscesses coincide with the high rates of amoebiasis (63/1,000 children) in refugees on the Thai-Cambodian border between 1987 and 1989.7

The most common extraintestinal manifestation is a liver abscess, with the parasite reaching the liver through the portal vein. The incidence of the disease is highest in Asia, where rates can reach 21/100,000 inhabitants/year. AHA predominantly affects middle-aged men (30–60 years). Risk factors include alcohol consumption and malnutrition (low body mass and hypoalbuminemia).

Pyogenic liver abscess (AHP) is formed by the accumulation of pus composed of numerous inflammatory cells, particularly neutrophils, and tissue debris.

The infection is associated with necrosis due to inflammation of the neighboring tissue. The word abscess may be a misnomer when used to define the pathological process caused by E. histolytica in the liver.

AHA is produced by the death of hepatocytes, either through apoptosis or necrosis. In general, the absence of inflammatory cells is justified due to the lysis of neutrophils by the protozoa that form the purulent abscess, described as "anchovy paste.

Cell death will continue to occur with the expansion of the abscess until the patient receives appropriate treatment. A study in hamster revealed that soon after seeding of E. histolytica in the liver parenchyma, inflammatory cells, consisting mainly of polymorphonuclear cells, surrounded the parasite to lead to lysis by hepatocytes.

AHP can be caused by a variety of organisms, including K. pneumoniae , Escherichia coli , and Burkholderia pseudomallei. Microbiology differs depending on the route of liver invasion. Infections can arise from the biliary tree (usually from an impacted gallstone), the circulation (portal vein, hepatic artery), an adjacent focus of infection, and penetrating trauma.

In Southeast Asia, patients are workers who are in contact with soil and water and have comorbidities such as diabetes, liver failure, kidney failure, and high alcohol consumption with risk of B. pseudomallei infection .

It is difficult to define the different microbiological pathogens that cause AHP. One reason for this difficulty is that the pus contained in the abscess often disappears after the administration of antibiotics, which may underestimate the presence of bacteria causing liver abscesses, and may also contribute to making differential diagnosis and diagnosis more difficult. choosing the most appropriate treatment.

This poses a selection bias whereby positive culture results may have a more resistant profile if patients had received antimicrobial treatment before culture. The number of sensitive pathogens that did not develop in the culture medium, as a result of previous antibiotic treatment, may also be underestimated.

Laboratory capacity for culture and germ identification may be limited in low- and middle-income settings. These problems mean that a negative culture does not necessarily express the absence of bacterial growth. Several studies have found that gram-negative bacilli such as E. coli , K. pneumoniae , anaerobes, S. milleri , and Staphylococcus aureus are important causative pathogens. The origin of the infection usually comes from the bile ducts, the intestinal tract or the portal system, with subsequent seeding in the liver.

In Taiwan, K. pneumoniae is an important pathogen that is frequently isolated. Although multidrug-resistant strains of K. pneumoniae are increasingly being identified in these settings , when this organism is identified in liver abscess, it is generally sensitive. A study found that patients with diabetes mellitus are at greater risk of developing liver abscess due to gas-forming K. pneumoniae , associated with a worse prognosis.

The hypothesis of the authors of that study is that the gas formation process may be favored by a high level of glucose in the tissues, which allows vigorous metabolism and the growth of K. pneumoniae . Toxic byproducts of inflammation accumulate and are cleared in the circulation in a delayed manner due to microangiopathy that delays transport of the end products out of the lesion. This suggests that good glycemic control is also important to control infection and improve clinical outcome.

Melioidosis is a major cause of liver abscess in Southeast Asia. The infection is caused by B. pseudomallei , a saprophytic gram-negative bacillus found in the environment. Rice farmers, who work in close contact with the soil and water, and people with weakened immune systems, such as diabetics, kidney or liver failure, or those suffering from thalassemia, are at greater risk of contracting infection.

Transmission of the pathogen is by ingestion, inhalation or inoculation, and can cause various types of infections such as sepsis, pneumonia and abscesses. In another study from Taiwan, the majority (70% n = 3.1/44) of liver abscesses were found to have multiple lesions.

More than a third (n = 160) of the cases underwent percutaneous incision and drainage while splenectomy was performed in 2 cases. Although the incidence of the disease remains to be established, the increased use of microbiology services shows that the disease is endemic throughout Cambodia.

The clinical score of amoebic and AHP is indistinguishable. Patients usually present with fever and pain on palpation in the right upper quadrant. Although laboratory tests are often abnormal leukocytosis (predominantly neutrophils); elevated inflammatory markers (e.g., C-reactive protein), elevated alkaline phosphatase; liver function tests? They have no real value to differentiate amoebic from AHP.

Imaging techniques such as ultrasound and computed tomography (CT) are useful tools to demonstrate an occupying lesion in the liver and confirm the presence or absence of a liver abscess, but may not reliably differentiate AHP from AHA.

AHA most commonly occurs as a lesion in the right lobe of the liver, but can be present in the left lobe and be multiple. For the detection of liver abscesses, CT has greater sensitivity (97%) than ultrasound (85%), although this modality may not always be accessible in resource countries. low and medium.

The gold standard for diagnosing AHP is fine needle aspiration to obtain specimens for culture.

This is not the case for AHA, as parasite culture is insensitive and not routinely available in clinical laboratories.

Microscopy also lacks sensitivity as trophozoites are seen in <25% of cases. The appearance of the aspirate may provide some information about the cause of the liver abscess. In general, AHA is odorless, chocolate brown, thick-walled, commonly known as anchovy paste, while AHP is usually purulent and foul-smelling, particularly as a result of anaerobic infection. Although this may be useful, its role for differential diagnosis remains uncertain.

Blood cultures are an important adjunct to the diagnosis of AHP and, although their yield is usually lower than that of aspiration of pus from a liver abscess, they can provide useful information before patients begin antimicrobial treatment or undergo aspiration of the abscess. . Whenever a liver abscess is suspected, a blood culture is recommended.

Serology may be useful in travelers returning from high-endemicity areas and residing in low-endemicity environments. Due to long-term positivity after exposure, it has less value in endemic settings where patients may have been previously exposed. The test may also be falsely negative, as in cases of acute presentations, or depending on the patient’s immune response, the type of serological test, or the strain of the pathogen. Antigen testing may be useful in low- and middle-income settings.

Antigen detection tests (TechLab E. histolytica II Antigen Detection) detect the presence of the Gal/GalNAc antigen in serum, which is very sensitive (≥95%) and specific (100%, sensitivity decreases significantly in patients who have been previously treated with metronidazole. The accessibility of antigen detection tests may also be a potential barrier to their access in low- and middle-income countries.

Another potential new marker, such as pyruvate phosphate dikinase, in the form of lateral flow test, shows potential for the diagnosis of AHA. Non-invasive, accurate, easily available and affordable tests in the field of diagnosis continue to be necessary for the diagnosis of AHA. Since most patients with AHA do not have intestinal symptoms, examination of stool for ova and parasites and antigen testing are not helpful and therefore. are not recommended.

Molecular testing of the contents of a liver abscess is reliable for the diagnosis of AHA. Although this test offers the potential to accurately diagnose Entamoeba infection , its availability in low- and middle-income countries is limited as it requires expensive equipment and supplies.

In high-income countries , the cause of liver abscess is usually determined using multiple diagnostic strategies, including blood cultures, serology for Entamoeba , aspiration of liver abscess for culture, and molecular and antigen testing.

In general, the presentation of patients in low- and middle-income countries is characterized by lack of initial response to antibiotic treatment, imaging showing the abscess without a proven cause, due to limited testing capacity. Low- and middle-income countries often lack essential microbiology resources and, when available, service utilization is often poor.

Sample collection should be performed before antibiotic administration. However, if the clinical presentation allows, in low- and middle-income settings, specimen collection is often done late and is generally reserved for patients who have not responded to antimicrobials. In these settings, it is common for patients to be medicated before hospitalization, in pharmacies or private clinics (≥50% of all medical consultations in Asia).

The medications they receive in this way are of a wide variety, including antimicrobials. The reasons why patients prefer to receive medications from the pharmacy are multiple, including easy accessibility, the ability to purchase medication in small quantities, and familiarity with the seller.

Insufficient training of staff working in pharmacies gives rise to their lack of knowledge, added to the poor availability of products. It is also recognized that the drugs sold have insufficient regulation resulting in uncontrolled sales.

In low- and middle-income countries, antimicrobial guidelines generally recommend empiric treatment, targeting both amebiasis and the causes of AHP. As treatment is usually started before sample collection, the causative pathogen and the prevalence of either of the 2 diseases are not entirely clear.

Antibiotic recommendations, with the selection of the most appropriate antimicrobials for the treatment of liver abscess, are hampered by the lack of local microbiological data. As a result, recommendations are often not adapted to the local environment and are borrowed from other environments.

AHAs are managed medically, while infections and AHP require drainage by repeated needle aspiration or percutaneous catheter, and appropriate antimicrobial treatment. Surgical drainage is usually reserved for complicated cases, although it has now been replaced by less invasive methods such as.

The mainstay of treatment for AHAs is metronidazole or tinidazole, orally, for 10 days or 5 days, respectively. This is followed by administration of a luminal agent such as paromomycin, for 5-10 days, to eradicate any remaining cysts in the intestinal tract. Most cases of AHA respond to medical treatment, while patients who do not respond to this treatment should undergo drainage.

Drainage is indicated in complications of infection, which include patients who have bacterial infection (either de novo or secondary to drainage) and patients at high risk of AHA rupture.

Treatment of AHP has evolved over the years, from open surgical drainage to imaging-assisted percutaneous drainage. There is uncertainty regarding which type of liver abscess should receive antimicrobials alone or undergo drainage. Currently, it is recommended that liver abscesses <3 cm be treated medically.

Aspirations of liver abscesses are effective and, in a high percentage of patients, lead to resolution. Incrementally repeated aspiration increases the likelihood of improvement after each aspiration.

The use of needle aspiration is an attractive option for low- and middle-income settings where availability of materials is limited. In these settings it is preferable to avoid inserting a drain, as they can be difficult to manage and be a source of secondary infections. The selection of an appropriate antibiotic differs depending on the pathogen isolated, the susceptibility pattern, and local epidemiology.

The prognosis of AHP depends on the time it takes to make the diagnosis. Patients with late diagnosis are more likely to require medical treatment with drainage. Patients who present with shock, renal failure, or acute respiratory failure are likely to experience a poor outcome.

Worldwide, E. histolytica is a major cause of mortality, second only to malaria as a cause of death from parasitic disease. AHA is a uniformly fatal disease if left untreated. Timely treatment of AHA achieves a favorable result. Ruptured and complex abscesses are associated with higher mortality.

In low- and middle-income settings, both amoebic liver abscesses and pyogenic liver abscesses are common and their clinical presentations are similar. Current diagnostic tests have limitations in their implementation in low- and middle-income settings and, as a result, accurate identification of the causal pathogen is problematic. This leads to issues related to the optimal management of liver abscesses in these deprived settings.

Despite limitations in sensitivity and availability, all patients with suspected liver abscess should have blood cultures performed. Large pyogenic abscesses require drainage or aspirations, which are appropriate therapeutic modalities for low- and middle-income settings. Culture of the liver aspirate should always be performed to ensure antimicrobial therapy.

There are currently few tests available for the rapid and affordable diagnosis of AHA in settings where infection is common. The introduction of a reliable diagnostic test at the bedside, e.g. Serum antigen testing for AHA in deprived settings would increase their detection rates.

The treatment of ALA is mostly medical, and thus, a more precise diagnosis would avoid drainage procedures and subsequent complications. This would also allow a reduction in the empirical use of antimicrobials for the treatment of AHP. and would reduce selection pressure for the development of antimicrobial resistance.

One area of ​​consideration for research could be the effectiveness of routine blood cultures and aspirations of abscesses amenable to drainage. Although this would not be feasible for small abscesses, macroscopic observation and analysis of the aspirate for E. histolytica , using antigen or molecular and microbiological tests, could be useful in order to stratify patients and decide which therapeutic protocol. would be the most appropriate. This invasive approach would mean that patients with E. histolytica infection would have an aspirate to clear the co-infection.