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Address for correspondence: Dr Sunil Taneja M.D., D.M., Assistant Professor, Department of Hepatology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India. Tel.: +91 9592160444.
Diagnosis and management of tuberculosis (TB) in patients with cirrhosis remains challenging. We studied the clinical spectrum, diagnosis, and management of TB along with the assessment of the diagnostic utility of various laboratory investigations in this cohort.
Methods
A retrospective review of records of patients with cirrhosis (July 2017 and December 2019) was done. Out of 30 patients with cirrhosis and TB, 20 patients with pleural/peritoneal TB (cases) were compared with 20 consecutively selected spontaneous bacterial peritonitis (SBP) controls. Composite of clinical, laboratory, radiologic features and response to antituberculosis therapy (ATT) was taken as the gold standard to diagnose TB.
Results
Extrapulmonary TB (EPTB) (n = 23, 76.7%) was more common. Overall, 9 (30%) patients presented with ATT-induced hepatitis. Patients with pleural/peritoneal TB had less severe hepatic dysfunction as compared to SBP group with significantly lower CTP [8 ± 1.5 vs. 9 ± 1.7 (P = 0.01)], MELD [16.3 ± 5.8 vs. 20.2 ± 6.6 (P = 0.02)] and MELD-Na [18.8 ± 5.9 vs. 22.5 ± 7.1 (P = 0.03)] scores. Median ascitic/pleural fluid total protein [2.7 (2.4–3.1) vs. 1.1 (0.9–1.2); P < 0.0001] and adenosine deaminase (ADA) levels [34.5 (30.3–42.7) vs. 15 (13–16); P < 0.0001] were significantly higher in the TB group. Total protein levels had a sensitivity and specificity 81% and 93.3%, respectively, at cut off value of >2 g/dl with an AUROC of 0.89 [(0.79–0.96); P < 0.001] whereas ADA levels at cutoff >26 IU/L showed 80% sensitivity and 90% specificity to diagnose pleural/peritoneal TB with an AUROC of 0.93 [(0.82–0.97); P < 0.001]. Only 11 (36.7%), and 8 (26.6%) patients showed positivity on GeneXpert and mTB-PCR, respectively. Patients with Child-Turcotte-Pugh scores of ≤7 and 8–10 tolerated well two and one hepatotoxic drugs, respectively.
Conclusions
EPTB is more frequent in patients with cirrhosis. Relatively lower cutoffs of ascitic/pleural fluid total protein and ADA may be useful to diagnose EPTB in patients with high pretest probability. Individualized ATT with close monitoring and dynamic modifications is effective and well-tolerated.
and limited accuracy of the available tests. Mycobacterium tuberculosis (MTB) culture takes 6–8 weeks. Laparoscopy with peritoneal biopsy, which is the gold standard to diagnose peritoneal TB, may not be feasible in patients with cirrhosis due to coagulopathy and thrombocytopenia. Newer nucleic acid amplification tests (NAATs) such as GeneXpert MTB/RIF (GeneXpert) and multiplex TB-polymerase chain reaction (mTB-PCR) have shown good sensitivity and specificity in sputum positive TB
Xpert ® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults (Review) Xpert ® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.
Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens.
Apart from the diagnostic challenge, the management of these patients is an arduous task with no consensus on the use of first-line antituberculosis therapy (ATT). Isoniazid, rifampicin, and pyrazinamide are hepatotoxic
To address the aforementioned gaps in knowledge, we studied the clinical spectrum, diagnosis, and management of TB in patients with cirrhosis. A special emphasis was laid on evaluating the ability of ascitic/pleural fluid investigations to diagnose and discriminate peritoneal and/or pleural TB from spontaneous bacterial peritonitis (SBP) and/or empyema (SBE).
Material and methods
Ethical Approval
All procedures involving human participants were done in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. The protocol was approved by the Institute’s ethics committee (PGI/INT/IEC/2020/1327) and adhered to Good Clinical Practice guidelines.
Study Participants
We retrospectively screened inpatient and outpatient records of all patients who presented to the Liver clinic of our institute between July 2017 and December 2019. Patients with cirrhosis, diagnosed and treated for TB, were considered for enrollment based on inclusion and exclusion criteria (Supplementary Figure 1). Twenty consecutive patients with SBP were taken as controls for comparison with pleural/peritoneal TB (cases). The study was approved by the Institute’s Ethics Committee and adhered to the Declaration of Helsinki.
Study Definitions
Diagnosis of Tuberculosis
Pulmonary TB was diagnosed if there was sputum positivity for acid-fast bacilli (AFB)/MTB by Ziehl-Neilson (ZN) staining or Gene Xpert or mTB-PCR and/or if there were chest imaging (X-ray/computed tomography, CT) findings consistent with TB. Diagnosis of extrapulmonary TB was mostly presumptive and was based on the combination of clinical, laboratory, and/or radiologic features along with the response to ATT in the absence of pulmonary involvement. If ascitic or pleural fluid or other appropriate body specimen was found to be positive for AFB/MTB by ZN staining or Gene Xpert or mTB-PCR or if there was a characteristic finding of TB on histopathology, then the diagnosis of EPTB was considered definite.
Response to treatment
Subjective and/or objective improvement in presenting symptoms such reduction in ascites/regaining of diuretic responsiveness (reduced dose of diuretics) and/or resolution of pleural effusion and/or cold abscess and/or regression of lymphadenopathy depending on site of tubercular involvement.
ATT-induced hepatitis or ATT-DILI
ATT-induced hepatitis in patients with cirrhosis was defined as a rise in transaminases by >2 times the baseline value or bilirubin >2 mg/dl, after exclusion of other possible causes.
Control Definition (Spontaneous Bacterial Peritonitis)
SBP was diagnosed if the ascitic fluid absolute polymorphonuclear leukocyte (PMN) count was ≥250 cells/ml with or without culture positivity in the absence of any intra-abdominal or surgically treatable source of infection.
was based on clinical, radiological, histological, and/or liver stiffness measurement (LSM) of ≥12.5 Kpa. The severity of cirrhosis was determined by Child-Turcot-Pugh (CTP),
Demographic characteristics, history, clinical examination, and available laboratory and radiological investigations were recorded and analyzed. Ascitic and/or pleural fluid investigations comprising of total and differential leukocyte counts with biochemistry and microbiological parameters encompassing total protein, sugar, serum ascitic albumin gradient (SAAG)/Serum pleural fluid albumin gradient (SPAG), Gram staining, and bacterial culture were also noted. Specific investigations for diagnosis of TB, including microscopy for AFB using ZN staining, adenosine deaminase (ADA) level determination using Giusti method,
Comparison of the real-time PCR method and the gen-probe amplified Mycobacterium tuberculosis direct test for detection of Mycobacterium tuberculosis in pulmonary and nonpulmonary specimens.
Medical records were meticulously reviewed for ATT used with dosage, duration, dose modifications, adverse events, and treatment discontinuations if any. Any improvement or deterioration in the patient’s clinical symptoms and investigations were recorded.
Statistical Analysis
Statistical analysis was done using SPSS software version 22.0 (SPSS Inc., Chicago, IL). The results of quantitative variables are presented as mean with standard deviation (SD) and/or median with 95% confidence interval (CI), depending on distribution attributes and as proportions with percentages for qualitative variables. Comparison between groups was made using Chi-square and Fischer exact tests for categorical variables and student’s t-test and Mann–Whitney U-test for parametric and nonparametric variables, respectively. Diagnostic utility of ADA and ascitic fluid protein was assessed using sensitivity and specificity at various cutoffs based on the area under respective receiver operator curves (AUROC) using clinical diagnosis and response to ATT as the gold standard. A P-value of ≤0.05 was considered as statistically significant.
Results
Patient Recruitment and Demographic Variables
Out of 40 patients with cirrhosis and TB, thirty cases fulfilling the inclusion criteria were included (Supplementary Figure 1). Among the 30 patients with cirrhosis and TB, 20 cases with pleural/peritoneal involvement (cases) were compared with 20 consecutive patients with cirrhosis and SBP (controls). The baseline demographic characteristics and etiology of cirrhosis were comparable between the two groups, as shown in Table 1.
Table 1Baseline Characteristics of the Pleural/Peritoneal Tuberculosis and Spontaneous Bacterial Peritonitis Groups.
Pleural/peritoneal Tuberculosis Group (n = 20)
Spontaneous Bacterial Peritonitis Group (n = 20)
P
Age (median, 95%CI), years
49.5 (44.2–51)
52.5 (46.2–56)
0.43
Sex (Males: Females)
19:1
18:2
0.32
Etiology of chronic liver disease
Alcohol
11 (55%)
9 (45%)
0.52
Chronic hepatitis C
3 (15%)
2 (10%)
Autoimmune hepatitis
2 (10%)
1 (5%)
Nonalcoholic fatty liver disease
2 (10%)
4 (20%)
Cryptogenic
1 (5%)
1 (5%)
Chronic hepatitis B
1 (5%)
2 (10%)
Chronic Budd Chiari syndrome
–
1 (5%)
CTP Class
CTP-A
2 (10%)
1 (5)
0.04
CTP-B
14 (70%)
10 (50%)
CTP-C
4 (20%)
9 (45%)
Baseline Severity Scores (mean ± SD)
CTP Score
8 ± 1.5
9 ± 1.7
0.01
MELD
16.3 ± 5.8
20.2 ± 6.6
0.02
MELDNa
18.8 ± 5.9
22.5 ± 7.1
0.03
CTP-Child Turcotte Pugh Score; MELD-Model for End-Stage Liver Disease; MELDNa-Model for End-Stage Liver Disease with Sodium.
Spectrum of Tubercular Involvement and Clinical Presentation
EPTB (n = 23,76.7%) was much more common than PTB (n = 7, 23.3%) (Table 2). On comparing the clinical presentation of patients with pleural/peritoneal TB and SBP, fever was the most common presenting complaint in both the groups [TB group: n = 13 (65%), SBP group: n = 10 (50%)], followed by pain abdomen in 10 (50%) and 8 (40%) patients with TB and SBP, respectively. Four (20%) patients in the TB group presented with new-onset ascites, whereas diuretic intractable ascites with or without AKI were seen in 5 (25%) and 11 (55%) patients with TB and SBP, respectively. Jaundice as a presenting complaint was seen in 5 (25%) cases with pleural/peritoneal TB, which was attributed to ATT-DILI. Only 2 (10%) patients in each group were asymptomatic at presentation.
Overall, respiratory symptoms of dyspnea [n = 7 (23.3%)] and productive cough [n = 7 (23.3%)] were seen only in patients with pleural and/or lung parenchymal involvement. Acute upper gastrointestinal bleeding (n = 5, 25%), hepatic encephalopathy (n = 5, 25%) and concomitant infections (n = 7, 35%) were seen exclusively in the SBP group (Supplementary Table 1).
Baseline Laboratory Investigations and Severity of Cirrhosis
Patients with pleural/peritoneal TB had less severe hepatic dysfunction as compared to SBP group with significantly lower CTP [8 ± 1.5 vs. 9 ± 1.7 (P = 0.01)], MELD [16.3 ± 5.8 vs. 20.2 ± 6.6 (P = 0.02)] and MELD-Na [18.8 ± 5.9 vs. 22.5 ± 7.1 (P = 0.03)] scores. CTP class C was more frequent in SBP group [9 (45%) vs. 4 (20%) (P = 0.04)] (Table 1). SBP patients had significantly lower hemoglobin [9.8 (8.9–10) vs. 10.4 (9.8–11.9) (P = 0.02)], higher creatinine [1.4 (1.2–1.9) vs. 1 (0.9–1.2) (P = 0.03)] and INR [1.8 (1.4–1.9) vs. 1.5 (1.4–1.7) (P = 0.05)] whereas other baseline biochemical parameters were comparable between the two groups (Supplementary Table 2).
Cytological and Biochemical Characteristics of Ascitic and/or Pleural Fluid
On comparing peritoneal and/or pleural EPTB (n = 20) cases with SBP (n = 30) group, patients with TB had significantly higher lymphocyte percentage [85% (75–94) vs. 18% (12–23) (P < 0.0001)] whereas PMN cells were significantly higher in patients with SBP [82 (77–88) vs. 15 (6–25) (P < 0.0001)] (Table 3). Median total protein [2.7 (2.4–3.1) vs. 1.1 (0.9–1.2); P < 0.0001] and ADA levels [34.5 (30.3–42.7) vs. 15 (13–16); P < 0.0001] were significantly higher in TB group (Supplementary Figures 2 and 3). Total protein levels had a sensitivity and specificity 81% and 93.3%, respectively at cut off value of >2 g/dl with an AUROC of 0.89 [(0.79–0.96); P < 0.001] whereas ADA levels at cutoff >26 IU/L showed 80% sensitivity and 90% specificity to diagnose pleural/peritoneal TB with an AUROC of 0.93 [(0.82–0.97); P < 0.001] (Figure 1, Figure 2).
Table 3Ascitic Fluid Cytology and Biochemical Analysis Among the Pleural/Peritoneal Tuberculosis and Spontaneous Bacterial Peritonitis Patients.
Ascitic/Pleural fluid parameter [median (95% CI)]
Pleural/Peritoneal Tuberculosis (n = 20)
Spontaneous Bacterial Peritonitis (n = 20)
P
SAAG/SPAG
1.3 (1.2–1.4)
1.8 (1.6–1.8)
<0.0001
TLC (cells/ml)
320 (220–576)
550 (460–658)
0.34
Polymorphonuclear cells (%)
15 (6–25)
82 (77–88)
<0.0001
Lymphocytes (%)
85 (75–94)
18 (12–23)
<0.0001
Sugar (mg/dL)
114 (97–145)
133 (121–145)
0.07
Total protein (g/dL)
2.7 (2.4–3.1)
1.1 (0.9–1.2)
<0.0001
ADA (IU/L)
34.5 (30.3–42.7)
15 (13–16)
<0.0001
SAAG-Serum-Ascitic Albumin Gradient; SPAG-Serum-Pleural fluid Albumin Gradient; TLC-Total Leucocyte Count; ADA-Adenosine Deaminase.
Figure 1Area under receiver operator curve (AUROC) for total protein levels in respective body fluids to diagnose pleural and/or peritoneal tuberculosis.
Figure 2Area under receiver operator curve (AUROC) for adenosine deaminase (ADA) levels in respective body fluids to diagnose pleural and/or peritoneal tuberculosis.
All the seven PTB patients had positive sputum GeneXpert, whereas 5 (71.4%) patients had sputum AFB positivity, and 6 (85.7%) patients had mTB-PCR positivity. However, among the 23 EPTB cases, only one had AFB positivity (on aspiration cytology of retroperitoneal lymph node) with detection of MTB by GeneXpert and mTB-PCR in only 4 (17.3%) and 2 (8.6%) patients, respectively. Overall, out of 30 patients with TB, only 6 (20%), 11 (36.7%), and 8 (26.6%) patients showed detection of MTB/AFB on microscopy, GeneXpert, and mTB-PCR, respectively (Supplementary Table 3).
Radiological Evaluation in TB Patients
Among 23 patients with EPTB, 10 (43.5%) patients had pleural effusion (5 TB effusion, 3 pleuroperitoneal TB, 2 right-sided transudative effusion). Thirteen (56.5%) had no lung parenchymal abnormality on chest imaging that suggested active PTB. Ascites, peritoneal or omental thickening, peritoneal enhancement, and/or hypoattenuating necrotic intra-abdominal lymph nodes were seen in 18 (78.3%), 4 (17.3%), 2 (8.6%), and 4 (17.3%) patients on abdominal contrast-enhanced CT. Ascites was loculated in only 3 (16.7%) patients (Supplementary Table 4).
ATT: Combinations, Modifications, Duration, and Side-effects
Patients with a CTP score of ≤7 received two, and those with a CTP score between 8 and 10 received one hepatotoxic drug. Rifampicin was the drug of choice in all patients receiving a single hepatotoxic drug. Nine (30%) patients who presented with ATT-DILI were initiated on all the three first-line hepatotoxic ATT drugs simultaneously in peripheral centers before being referred to our institute. Among the hepatic-safe regimens, intravenous amikacin was used in 7 (23.3%) patients, whereas intramuscular streptomycin was used in 2 patients. Levofloxacin was the most frequently used second-line drug (n = 26,86.6%) and showed no major side effects. AKI due to amikacin was encountered in 4 out of 7 patients within 2 weeks of initiation and was replaced by oral levofloxacin. The composition of the ATT regimens used was dynamic, and their duration was variable ranging between 9 and 18 months (Table 4).
Table 4Antituberculosis Therapy (ATT) Regimens, Duration and Side-effects.
All patient underwent regular recalculation of CTP scores after repeating clinical and laboratory tests during follow up and ATT was modified accordingly and individualized.
Patient who had ATT-induced hepatitis at presentation received full dose first line ATT-regimen elsewhere and then referred to our institute; all had previously undiagnosed underlying chronic liver disease.
1
7B
Peritoneal
HRE
11
None
2
7B
Disseminated
HREL-3 months; HRE-7 months
10
None
3
7B
Peritoneal
HREL
12
None
4
10C
Peritoneal
LEA-1 month; LE-2 months; LER-15 months
18
Acute Kidney Injury due to Amikacin
5
7B
Peritoneal
LER-1 months; HRE-11 months
12
None
6
8B
Peritoneal
REL-2 months; HRE-9 months
11
None
7
10C
Pleuroperitoneal
LEA-1 month; LER-12 months
13
None
8
11C
Pleural effusion
LE-1 month; RLE-12 months
13
ATT-induced hepatitis at presentation (H, Z)
9
9B
Pulmonary
HRZE-14 days; LEA-1 month; RLE-11 months
12
ATT-induced hepatitis on H and Z, Acute Kidney Injury with Amikacin
b All patient underwent regular recalculation of CTP scores after repeating clinical and laboratory tests during follow up and ATT was modified accordingly and individualized.
c Patient who had ATT-induced hepatitis at presentation received full dose first line ATT-regimen elsewhere and then referred to our institute; all had previously undiagnosed underlying chronic liver disease.
Cirrhosis-related immune dysfunction contributes to a higher incidence of active TB and false-negative laboratory investigations, especially tuberculin skin tests and interferon-gamma release assays.
The diagnostic difficulty may lead to delayed initiation of ATT and increased morbidity and mortality. This study highlights that early diagnosis with appropriate investigations and carefully selected ATT regimens can improve the overall outcome in this difficult-to-treat cohort.
The majority of TB patients in our study were middle-aged males. The older age of our cohort as compared to the general population with TB can be attributed to the exclusive inclusion of patients with cirrhosis. The most common etiology of cirrhosis in our study was alcohol, which has also been reported to be an independent risk factor for TB in multiple previous studies.
Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report.
whereas more frequent EPTB in cirrhosis poses a diagnostic conundrum. A high index of suspicion for TB must be kept in patients with cirrhosis due to the nonspecific and diverse clinical presentations of EPTB. Constitutional symptoms, like anorexia, fever, and weight loss, which are clinically helpful in making a diagnosis of TB, may not be reliable in patients with cirrhosis.
More than three-fourths of patients in our study had EPTB with peritoneal and/or pleural involvement as opposed to TB-lymphadenitis in immunocompetent individuals.
Tuberculous peritonitis in cirrhotic patients: comparison of spontaneous bacterial peritonitis caused by Escherichia coli with tuberculous peritonitis.
have reported a similar higher incidence of EPTB in patients with cirrhosis. Higher incidence of EPTB can be explained by an inadequate initial immune response to contain MTB, as well as increased risk of reactivation in cirrhosis.
Lower mean CTP and MELD scores in the TB group as compared to the SBP group in our study suggests that the development of SBP may need a greater degree of liver dysfunction and immune paresis. Similar observations were seen in an earlier study by Huang et al
in which the SBP was more common in CTP class C patients. New-onset ascites or recent loss of diuretic response in an appropriate clinical scenario may act as clinical cues to initiate work up for peritoneal TB.
Like previous studies, TB patients in our study had significantly higher median total protein and ADA levels than SBP patients. CD4+ T-lymphocytes mediated Th1 response is the primary immune response to MTB, and activity of ADA correlates with the number, degree of maturation, and stimulation of lymphocytes.
Multiple studies from the Southeast-Asian region have shown the similar performance of ADA to diagnose ascitic/pleural TB, with cutoffs ranging between 30 and 45 IU/L however, these studies included patients without cirrhosis also.
which may be because of a higher number of patients with alcohol-related cirrhosis who have a greater degree of immune dysregulation, malnutrition, and sarcopenia.
Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens.
Only one EPTB patient showed positive ZN staining with just 4 (17.3%) and 2 (8.6%) patients showing positive GeneXpert and mTB-PCR, respectively. Similar low positivity rates of GeneXpert in body fluids have been reported from previous studies.
Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-infected patients. Comparison of LED fluorescent microscopy and the GeneXpert MTB/RIF assay in a district hospital in India.
Paucibacillary nature of EPTB likely results in poor positivity of NAATs. However, a positive result on NAATs along with corroboratory clinical findings should be sufficient to commence ATT without waiting for cultures.
In the present study, most patients had atypical radiological findings of EPTB. Nonspecificity of radiologic findings in EPTB, especially peritoneal and/or pleural TB, has been reported previously, especially in the patients with cirrhosis due to altered immune response.
Although radiologic evaluation may not be diagnostic of TB in patients with cirrhosis, it may be helpful to detect organ involvement and accessible sites for tissue acquisition.
Management of TB in cirrhosis is challenging and needs individualization. First, the diagnosis of TB should be certain before initiating ATT. Unfortunately, nearly 60% of patients receive empirical ATT
suggesting poor specificity of diagnostic tests. The second issue is of hepatoxicity of three first-line antitubercular drugs and poorly defined diagnostic criteria of ATT-induced hepatitis in patients with cirrhosis.
Our clinical practice is to stop hepatotoxic drugs if there is a relative rise of transaminases by >two times from baseline or a rise in bilirubin to >2 mg/dl. Nearly one-third of patients in our study presented with ATT-induced hepatitis likely due to the initiation of all three hepatotoxic antitubercular drugs simultaneously. This underpins the need for increasing awareness among the primary healthcare providers about the possibility of the presence of yet undiagnosed underlying chronic liver disease and the need for baseline evaluation of liver functions, especially in at-risk patients, before initiation of first-line ATT.
In our study, most patients showed gradual improvement in their CTP scores. Periodic recalculation of CTP score with the sequential addition of the most effective ATT drugs (Rifampicin and Isoniazid) is of paramount importance. Fluoroquinolones, including levofloxacin and ofloxacin, have shown good efficacy and safety as a part of hepatic-safe ATT regimen in patients with cirrhosis.
Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report.
However, the use of aminoglycosides like streptomycin and amikacin is limited in cirrhosis due to the risk of AKI and the presence of coagulopathy.
The treatment duration in our study ranged from 9 to 18 months depending upon baseline and dynamic changes in CTP score, ability to give first-line ATT drugs, and side effects leading to regimen modification. Carefully selected and individualized ATT with close follow up and concurrent management of underlying cirrhosis and its complications has shown satisfactory response in previous studies also with no effect of TB on mortality after one year of diagnosis and treatment.
The retrospective nature of our study limited our ability to accurately assess the initial clinical presentation, concurrent medications, compliance with diet restriction, the dose of diuretics, and any genetic associations with ATT-induced hepatitis in our study population. Information regarding tuberculin skin testing and MTB culture was missing. Since patients were seen by all authors in their respective wards and clinics, uniformity in ATT regimens and duration was not maintained. Such nonuniformity further stresses the need for consensus guidelines to manage such patients based on accurate and extensive data on the efficacy and safety of various ATT regimens. All SBP patients were admitted, which may have contributed to their higher CTP and MELD scores. As this is a single-center study, the cutoffs for total protein and ADA are only suggestive and may not be generalized.
Figure 3 outlines the proposed algorithm to manage TB in cirrhosis based on our experience.
Figure 3Proposed algorithm for diagnosis and management of extrapulmonary tuberculosis (EPTB) in patients with cirrhosis. TLC: Total leucocyte count; DLC: Differential leucocyte count; SAAG: Serum ascitic albumin gradient; SPAG: Serum pleural fluid albumin gradient; ADA: Adenosine deaminase; NAATs: Nucleic acid amplification tests; CECT: Contrast-enhanced computed tomography; AFB: Acid-fast bacilli; ATT: Antituberculosis therapy; CTP: Child-Turcotte-Pugh Score; LFT: Liver function tests; DILI: Drug-induced liver injury; AST: Aspartate aminotransferase; ALT: Alanine Aminotransferase.
EPTB is more common in cirrhosis, and reaching a conclusive diagnosis is often difficult. A high index of suspicion and relatively lower cutoffs of ascitic or pleural fluid total protein and ADA may be useful to diagnose EPTB in patients with high pretest probability. Individualized ATT with close monitoring and dynamic modifications is effective and well-tolerated by most patients resulting in excellent outcomes.
Credit authorship contribution statement
Saurabh Mishra: Data curation, formal analysis, investigation, methodology, project administration, validation, writing - original draft, writing - review and editing, and final approval of the manuscript.
Sunil Taneja: Conceptualization, data curation, formal analysis, investigation, methodology, supervision; project administration, validation, writing - review and editing, and final approval of the manuscript.
Arka De, Valliappan Muthu, Nipun Verma, Madhumita Premkumar: Data acquisition and analysis, project administration, writing - review and editing, and final approval of the manuscript.
Ajay Duseja, Virendra Singh: Data acquisition; supervision, project administration, writing - review and editing, and final approval of the manuscript.
Conflicts of interest
The authors have none to declare.
Funding
None.
Disclosure statement
Nothing to disclose.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
Xpert ® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults (Review) Xpert ® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.
Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens.
Comparison of the real-time PCR method and the gen-probe amplified Mycobacterium tuberculosis direct test for detection of Mycobacterium tuberculosis in pulmonary and nonpulmonary specimens.
Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report.
Tuberculous peritonitis in cirrhotic patients: comparison of spontaneous bacterial peritonitis caused by Escherichia coli with tuberculous peritonitis.
Rapid diagnosis of pulmonary and extrapulmonary tuberculosis in HIV-infected patients. Comparison of LED fluorescent microscopy and the GeneXpert MTB/RIF assay in a district hospital in India.
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