|SYSTEMATIC REVIEW OF CASE REPORTS
|Year : 2023 | Volume
| Issue : 3 | Page : 188-192
Isolated tubercular abscess in immunocompetent children: A systematic review of case reports
Rajkumar Kundavaram, Sourabh Singh, Amber Kumar, Shikha Malik, Girish Chandra Bhatt
Department of Pediatric Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
|Date of Submission||14-Jul-2023|
|Date of Decision||25-Jul-2023|
|Date of Acceptance||25-Jul-2023|
|Date of Web Publication||14-Aug-2023|
Dr. Girish Chandra Bhatt
Department of Pediatrics, All India Institute of Medical Sciences, Room No 1023, Academic Block, 1st Floor, Saket Nagar, Bhopal, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Background: Tuberculosis (TB) is a common disease, especially in low-income countries, with a varied clinical spectrum involving multiple organs. Although liver abscess can be seen in 70% of patients with miliary tuberculosis, isolated tuberculous liver abscess (ILTA) is rare in immunocompetent children. Liver involvement, though seen in up to 70% of patients as a part of miliary TB, isolated tuberculous liver abscess (ITLA) is rare in 13 children. Objective: The present systematic review focuses on demographic parameters, clinical presentations, duration of antitubercular treatment, and the need for surgical intervention and recurrence in children with tuberculous liver abscess. Methods: A comprehensive search was done in major databases PubMed and Google Scholar using defined search terms encompassing case reports or case series on isolated tubercular liver abscess in children. The identified reports underwent screening by three different authors for inclusion and exclusion criteria. Results: The median (interquartile range [IQR]) age of presentation was 9.5 (6.5) years, with a slightly higher prevalence in females (59%). The most common presenting symptom was fever (95%), followed by abdominal pain (68%). Hepatomegaly was seen in 90% of cases and jaundice in 16%. The median (IQR) duration of antitubercular treatment was 6 (4) months and surgical intervention was required for 14 (63%) children. The resolution time of the ITLA varied across the children, with a median (IQR) time being 2 (7) months. Conclusion: Pediatric tubercular liver abscess requires a high index of suspicion, particularly in endemic countries like India. Children with liver abscess should be evaluated for TB, if response to initial management is poor. Early diagnosis and prompt treatment with systemic antitubercular treatment are associated with a favorable outcome.
Keywords: Antitubercular therapy, hepatic abscess, pediatric
|How to cite this article:|
Kundavaram R, Singh S, Kumar A, Malik S, Bhatt GC. Isolated tubercular abscess in immunocompetent children: A systematic review of case reports. Indian Pediatr Case Rep 2023;3:188-92
|How to cite this URL:|
Kundavaram R, Singh S, Kumar A, Malik S, Bhatt GC. Isolated tubercular abscess in immunocompetent children: A systematic review of case reports. Indian Pediatr Case Rep [serial online] 2023 [cited 2023 Sep 30];3:188-92. Available from: http://www.ipcares.org/text.asp?2023/3/3/188/383619
Tuberculosis (TB) is a common disease in children, with varied clinical spectrum presenting with pulmonary, abdominal, neurological, skeletal, and disseminated forms. Although, following the introduction of Bacillus Calmette–Guérin (BCG) vaccine in the national immunization schedule of most of the countries, the incidence of TB has decreased, poverty, HIV, and drug resistance are contributing to the global resurgence of the TB epidemic. Nearly 75% of the cases of TB are pulmonary, with TB lymphadenitis being a common cause of extrapulmonary TB.
Liver involvement in TB is a rare manifestation. Liver involvement is typically observed as two forms: as a part of disseminated TB, or as a primary liver infection. Isolated hepatic involvement is rare and has a prevalence of approximately 0.34%. While up to 70% of patients with military TB have liver involvement, the incidence of hepatic involvement in children with pulmonary TB varies from 2.5% to 93%. Barring a study by Chen et al., showing a higher prevalence of tuberculous liver abscess in children, most other studies have reported that isolated tuberculous liver abscess (ITLA) is more common in adults.,, Tuberculous liver abscess is relatively uncommon, even in areas where Mycobacterium tuberculosis is prevalent, and usually occurs in conjunction with pulmonary or enteric TB.
Morphologically hepatic TB can be classified into three types. Diffuse involvement, diffuse parenchymal involvement, and focal or nodular lesions in the liver.
Levine's classification system identifies five distinct patterns of hepatic TB: (1) miliary TB which is characterized by the spread of tiny tubercular lesions throughout the liver, (2) concomitant hepatic and pulmonary disease, (3) primary (isolated) hepatic TB which is rare with liver being the only organ affected, (4) Tubercular hepatic abscess: which can lead to a variety of symptoms such as fever, abdominal pain, and jaundice, (5) Tubercular cholangitis in which TB infects the bile ducts within the liver.
The diagnosis of hepatic TB can be challenging as symptoms and signs are often nonspecific such as fever, vague abdominal pain, anorexia, and weight loss. Hepatomegaly is common, but jaundice is rare. Abnormalities of liver function test have also been reported. Accurate diagnosis of isolated hepatic TB may require invasive procedures such as biopsy, and treatment involves a combination of antitubercular therapy and procedures such as percutaneous aspiration, pigtail drainage, and intralesional infusion of antitubercular drugs. Few cases may need surgical excision. The appropriate duration of antitubercular therapy for liver abscess is a topic of debate, and a systematic review of existing studies will provide useful information. There are no prior systematic reviews of hepatic TB in children; therefore, we tried to synthesize the existing data on the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB in immunocompetent children.
| Methods|| |
We conducted a systematic review based on a prospectively registered protocol (PROSPERO CRD 42023432498; registered in 2023) to investigate various aspects of isolated tubercular liver abscesses in children. Our study aimed to explore the characteristics, clinical presentations, diagnostic methods, treatment approaches, outcomes, and complications reported in case reports. Our findings cover a wide range of information, including demographics, clinical manifestations, imaging modalities, diagnostic methods, the need for surgical intervention, abscess resolution time, BCG vaccination status, microbiological confirmation, and recurrences. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, as illustrated in [Figure 1].
|Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Flow diagram of the study selection process. *Articles,, which are not available as full text on any platform, we tried contacting the publisher of journal for full text and contacting authors was not possible. TB: Tuberculosis|
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We conducted a comprehensive search in major databases, namely PubMed and Google Scholar, using a set of carefully chosen keywords such as “pediatric,” “children,” “adolescent,” “infant,” “preschool children,” “tuberculous liver abscess,” “tuberculosis hepatic,” “Mycobacterium tuberculosis,” and “liver.” This search encompassed case reports or case series on isolated tubercular liver abscess in pediatrics from the beginning of the databases' records until June 2023. The identified reports underwent screening based on predefined inclusion and exclusion criteria, and relevant data were extracted. To ensure comprehensiveness, we manually searched the reference lists of the identified studies for additional relevant research.
Inclusion criteria: Patients aged ≤18 years, diagnosis of tubercular liver abscess confirmed by microbiological culture, cartridge-based nucleic acid amplification test (CBNAAT), polymerase chain reaction (PCR), or histopathology; data on clinical characteristics, diagnostic methods, treatment outcomes, and prognostic factors being available; the study being must be peer-reviewed, original article published in English; the study including a clear definition of tubercular liver abscess.
Exclusion criteria: Patients having disseminated TB, TB in immunocompromised patients, studies reporting tubercular liver abscess in combination with other forms of TB, or studies reporting tubercular liver abscess in patients with underlying liver disease.
Two reviewers (SS and KR) conducted a rigorous two-stage selection process for the studies. Initially, they screened the titles and abstracts of the identified case reports/series, followed by a detailed assessment of the full text for eligibility. Any disagreements were resolved through discussion involving a third reviewer (GB). Case reports/series that did not meet the inclusion criteria were excluded based on predefined criteria.
The systematic review focused on various outcomes pertaining to isolated tubercular liver abscesses in children, as reported in case reports. These outcomes encompassed the assessment of microbiological confirmation, including the presence of positive tests for M. tuberculosis or other diagnostic methods confirming TB. The review also examined the resolution time of the abscess, measuring the duration from the initiation of treatment to the complete resolution of the abscess. Evaluation of the need for surgical intervention involved considering any surgical procedures such as abscess drainage or aspiration mentioned in the case reports. In addition, the review analyzed the BCG vaccination status to compare the occurrence of the disease between vaccinated and nonvaccinated children. Finally, the occurrence of recurrence was explored, specifically looking for subsequent episodes of liver abscesses mentioned in the case reports.
Case reports and case series, being uncontrolled study designs, carry an increased risk of bias. To assess methodological quality, we employed the framework proposed by Murad et al., considering selection, ascertainment, causality, and reporting domains. Both authors reviewed and assessed all papers. Significant heterogeneity existed among the case reports, limiting our ability to address publication bias and selective reporting. This tool provides a systematic approach to evaluating the methodological quality and risk of bias in studies.
| Results|| |
Eighteen case reports and one review article were reviewed [Table 1]. These provided case descriptions of 22 children diagnosed with isolated tubercular liver abscess.
|Table 1: General characteristics of studies included along with their quality assessment score|
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Based on assessment tool developed by Murad et al., the total scores obtained for the included case reports ranged from 3 to 6, with a median score of 6, indicating that case reports in our systematic review were of moderate-to-high quality. However, the specific criteria and domains assessed by the tool to get a comprehensive understanding of the quality of the studies should be considered.
The geographic distribution showed majority of the cases were from developing countries. It is worth noting that the majority of the cases are from India, which suggests a higher prevalence or reporting of isolated tubercular liver abscess in our country. The age of the children with ITLA ranged from 2 to 18 years, median (interquartile range IQR) was 9.5 (6.5) years. Gender distribution shows a slightly higher proportion of females (59%). Information on HIV status was available for 11 children. All of them tested negative for HIV. This observation indicates that HIV infection may not be directly associated with an increased risk of developing ITLA. It is important to note, however, that this conclusion is based on the available data and the assumption that HIV status was accurately reported for the included cases. Data regarding BCG vaccination were provided for six children. All these children had received BCG vaccination.
Specific diagnostic tests were conducted on the included cases of ITLA. Here are the findings based on the available data:
The Mantoux test was performed in 16 children. Out of these, 5 (31%) children had a positive result.
Acid-fast bacillus staining
Acid-fast bacillus (AFB) staining done in 18 children, with 12 (66%) showing positive AFB staining.
Cartridge-based nucleic acid amplification test
CBNAAT was performed on pus samples from 12 children, and all of them (100%) yielded positive results.
Mycobacterial culture was performed on samples from 8 children. Among them, 5 (62.5%) children showed the growth of Mycobacterium in the culture.
Multiplex polymerase chain reaction
Among the 22 children, three children underwent multiplex PCR to differentiate tubercular from nontubercular Mycobacterium. However, no specific findings or results were mentioned regarding this procedure in the information provided.
Information regarding the history of TB contact was available for ten children. One child had a documented history of contact with TB.
A varied clinical presentation has been seen with ITLA [Table 2], with fever (95.45%) being the most common symptom followed by abdominal pain (68.18%). Hepatomegaly was seen in 90% of children and 16.16% had jaundice. No bleeding manifestations or encephalopathy was seen.
|Table 2: Symptom presentation in children having isolated tuberculous liver abscess (N=22)|
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Abdominal ultrasonography was performed in 21 (95.4%) cases, computed tomography (CT) of the abdomen in 12 (54.5%) cases, magnetic resonance imaging abdomen in 2 (9.1%) cases, and Endoscopic Retrograde cholangiopancreatography (ERCP) in 1 (4.5%) case [Table 3].
|Table 3: Imaging modalities used in children having isolated tuberculous liver abscess (N=22)|
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For the treatment of ITLA, standard four antitubercular drugs (HRZE) were used with 18 (81.81%) children receiving a four-drug therapy (HRZE) followed by two drugs (HR). Pigtail catheter was inserted in three children. The treatment duration ranged from 6 weeks to 18 months, with a median (IQR) duration of 6 (4) months.
The resolution time of the ITLA varied significantly in the cases, ranging from 14 days to as much as 19 months after starting treatment, with a median (IQR) time for resolution of 2 (7) months. Immediate resolution was seen in patients who underwent laparotomy (29.41%). Recurrence was reported in 1 (5.5%) case.
Surgical intervention was required in 15 children with ITLA [Table 4].
|Table 4: Need for surgical intervention in children with isolated tuberculous liver abscess (N=22)|
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The children were followed up on an outpatient basis for a variable duration ranging from 1 month to 48 months. The median follow-up duration was 9.5 months.
| Discussion|| |
Childhood TB constitutes around 10%–20% of total TB cases in countries with a high burden like India, and it accounts for 8%–20% of TB-related deaths. Given the higher number of case reports from India, there may be a correlation between the high prevalence of TB and the occurrence of ITLA in immunocompetent children.
Our review indicates a rising trend in the number of case reports from 2011 to 2020 compared to the two previous decades. The median age being 9.5 years, the disease is relatively less common among infants or adolescents.
We only had information for a total of ten children regarding the history of TB contact. Among these children, only one child had a documented history of contact with TB. Although it appears that most children diagnosed with isolated tubercular liver abscess had no known contact, it is crucial to consider that the absence of a reported history of contact does not entirely rule out the possibility of TB exposure in these cases.
None of the children exhibited bleeding manifestations or encephalopathy, such as altered mental status, lethargy, and irritability in younger children, suggesting that none of the abscesses were complicated with liver failure. One child experienced a recurrence of the disease, suggesting that the Mycobacterium causing the abscess might not be susceptible to the standard HRZE treatment regimen. In addition to medical therapy, surgical interventions were required.
Interestingly, the duration of treatment with anti-TB therapy (ATT) varied, possibly due to the lack of clear guidelines for the diagnosis and management of ITLA. In the Indian context, the average treatment duration is around 6 months, while in developed nations, it extends to 18 months. On average, symptoms tend to resolve within approximately 2 months.
In low-resource settings, ultrasonography is recommended as a valuable modality for diagnosing and monitoring outcomes; however, radiological imaging may sometimes indicate lesions in the liver that resemble malignancies, potentially leading to unnecessary hepatic resection. The diagnostic tests employed included AFB staining and CBNAAT for TB. In the case of liver abscess, AFB staining of aspirated pus is a suitable diagnostic approach, particularly in low-resource countries. In the past, exploratory laparotomy or autopsy was frequently necessary for a definitive diagnosis, but now, biopsy is becoming increasingly common. Biopsy can produce false-negative results if necrotic tissue is obtained. In such cases, surgery may be necessary. In addition, it is essential to differentiate abscess from necrotic tumors, and TB can be diagnosed through culture, PCR, or pathology. Although caseous necrosis is not exclusive to TB, a positive outcome from anti-TB treatment supports the diagnosis indirectly.
The WHO recommendation for the treatment of drug-susceptible pulmonary TB includes isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) for 2 months, followed by 4 months of HRE. The optimal duration for treating hepatic TB is highly varied, but 6–12 months appears to be effective for most patients. The American Thoracic Society recommends 6–9 months for any extrapulmonary site, except TB meningitis. Percutaneous aspiration, pigtail drainage, intralesional infusion of isoniazid, or a combination of isoniazid and rifampicin, as well as surgical excision, might be required in few cases. In cases where the thick fibrous wall of the abscess cavity hinders drugs from reaching the intended target, local injection of drugs directly into the abscess cavity is recommended.
This systematic review has some limitations. First, the number of case reports included in the analysis is relatively small, which may limit the generalizability of our findings. Second, the case reports included in the analysis were conducted in different countries with different health-care systems, which may have had an impact on the results. Third, the case reports included in the analysis had different study qualities, with possibility of bias.
| Conclusion|| |
Although uncommon, tubercular liver abscess should be included in the differential diagnosis of liver abscess especially when there is a poor response to initial therapy. Identification requires a high index of suspicion, particularly in endemic countries like India. Pus samples from liver abscess should be sent for TB workup in patients with known risk factors for TB. Early diagnosis and prompt treatment with systemic ATT are associated with a favorable outcome.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]