Tuberculosis on two fronts: A case report of liver and stomach involvement in a patient

Abstract

Introduction

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis, primarily affecting the lungs but can also affect other organs. In 2021, 10.6 million people became ill with TB, and 1.6 million died. Abdominal TB is rare, accounting for 1–3 % of cases, and often involves the ileocecal region. Stomach and duodenal TB are uncommon and challenging to diagnose as they mimic other conditions. Hepatic TB is rarer, accounting for < 1 % of TB cases, and has non-specific symptoms such as fever, hepatomegaly, and weight loss.

Case presentation

A 26-year-old female healthcare worker experienced fatigue and abdominal pain in the epigastric and right upper quadrant areas, prompting her visit to a gastroenterology clinic. She did not have any other accompanying symptoms, such as nausea, vomiting, weight loss, fever, or night sweats, and upon examination, she exhibited mild epigastric tenderness without any mass. Laboratory tests revealed anemia, mild thrombocytosis, and elevated erythrocyte sedimentation rate. Upper endoscopy uncovered multiple small, clean-based ulcers in the antrum and bulb, and biopsies confirmed chronic granulomatous gastritis in the stomach and duodenum. Abdominopelvic ultrasonography showed heterogeneous liver parenchymal echogenicity and multiple small, ill-defined hyperechoic areas in both liver lobes. At the same time, CT scans of the chest, abdomen, and pelvis exhibited multiple hypodense lesions with peripheral rim enhancement in the liver and clear lungs. The patient was given anti-tuberculosis drugs and responded well. Follow-up after six months revealed no significant findings.

Conclusions

Clinicians in TB-endemic regions should maintain a high index of suspicion for gastrointestinal and liver TB in patients presenting with some abdominal and constitutional symptoms. The most sensitive imaging modality for hepatic TB is a CT scan, while the most specific diagnostic modality is a CT or Sono- guided liver biopsy.

Introduction

Tuberculosis (TB) is a chronic granulomatous disease caused by Mycobacterium tuberculosis. Infection usually occurs in the lungs, but other organs may also be affected. According to the World Health Organization, 10.6 million people (95 % UI: 9.9–11 million) became ill with TB in 2021, up 4.5 % from 10.1 million (95 % UI: 9.5–10.7) in 2020. A total of 1.6 million people died from TB in 2021 (including 187,000 people with HIV). TB is the 13th leading cause of death worldwide and the second leading infectious killer after COVID-19 (above HIV/AIDS) [1].

Abdominal TB is a relatively rare manifestation of TB, accounting for approximately 1–3 % of all cases and 12 % of extrapulmonary cases [2]. There is a tendency for tuberculosis to involve the ileocecal region, as it is one of the most common sites of gastrointestinal involvement. Stomach and even duodenal tuberculosis are uncommon and usually associated with pulmonary tuberculosis or immunodeficiency [3]. Primary gastric TB is usually a diagnostic challenge and may mimic peptic ulcer disease, neoplasia, or other conditions [4].

A rare type of extrapulmonary tuberculosis, hepatic tuberculosis (HTB), usually occurs in the context of miliary TB but accounts for less than 1 % of all tuberculosis cases [5]. Most of the symptoms of this disease are non-specific, which drives a delay in diagnosis, and include mild fever, hepatomegaly, respiratory distress, abdominal pain, and weight loss [6]. In other words, diagnosing HTB accurately is challenging because it lacks distinctive clinical symptoms and specific imaging manifestations, which can easily be mistaken for other diseases. In the present case, we describe a patient with abdominal pain and fatigue who had concurrent gastroduodenal and liver TB.

Case presentation

A 26-year-old female was evaluated in the gastroenterology clinic of our hospital because of fatigue and abdominal pain in the epigastric and right upper quadrant areas. Her pain was constant, aggravated with eating, and had started one month before admission. She had no experience of nausea, vomiting, weight loss, fever, or night sweats. She reported the same problems during the last year, for which she had intermittently taken proton pump inhibitors (PPIs). Her other medical history was alpha thalassemia. The patient had no past or family history of tuberculosis and had never been in contact with a symptomatic TB patient. She lives in southern Iran, is a healthcare worker, and has never smoked or consumed alcohol. She also denied any history of consuming unpasteurized milk or dairy products.

On examination, she had a normal temperature and vital signs. The cardiovascular and respiratory systems were within normal limits. The abdomen was soft with mild epigastric tenderness and without mass.

Laboratory studies revealed anemia, mild thrombocytosis, and elevated erythrocyte sedimentation rate. The total bilirubin level was 0.8 mg per deciliter; the aspartate aminotransferase was 38.75 IU per liter (standard limit up to 32), the alanine aminotransferase was 12.8 IU per liter, and the alkaline phosphatase was 293 IU per liter (standard limit up to 306). Human immunodeficiency virus (HIV) test and evaluation for hepatitis B and C with HBs Ag and HCV Ab were negative. Tumor marker results for Alpha-fetoprotein, Carcinoembryonic antigen, and Carbohydrate antigen 19–9 were in the normal range. Moreover, blood electrolyte levels were normal, as were the results of kidney function tests and urine analyses. Other laboratory test results are shown in Table 1.

Table 1.

Laboratory Data.

Variable	Patient result	Reference Range
Hematocrit (%)	29.7	34–47
Hemoglobin (g/dl)	9.0	11.7–15.5
White-cell count (per μl)	6900	4000–11000
Differential count (%)
Neutrophils	56.6
Lymphocytes	24.7
Monocytes	15.5
Eosinophils	2.9
Platelet count (per μl)	486000	140000–440000
Mean corpuscular volume (fl)	51.7	81–100
Mean corpuscular hemoglobin (pg)	15.7	27–34
Mean corpuscular hemoglobin concentration (g/dl)	30.3	32–36
Red-cell distribution width (%)	24.1	10.6–15.7
Prothrombin time (sec)	15.50	11.5–14.5
Prothrombin-time international normalized ratio	1.17	0.9–1.1
Activated partial-thromboplastin time (sec)	43.7	25–45
Lactate dehydrogenase (U/liter)	301	< 480
Alanine aminotransferase (IU/liter)	12.86	5–33
Aspartate aminotransferase (IU/liter)	38.75	5–32
Alkaline phosphatase (IU/liter)	293	64–306
Total bilirubin (mg/dl)	0.80	0.1–1.2
Direct bilirubin (mg/dl)	0.18	< 0.3
C-reactive protein	+ +	Negative
Erythrocyte sedimentation rate (mm/hr)	54	0–20
BetaHCG (IU/L)	0.31	< 5 Negative

Upper endoscopy examination displayed multiple small, clean-based ulcers in the antrum and bulb (Fig. 1).

Fig. 1.

Upper endoscopy. These pictures show clean base ulcers in the antrum (right) and bulb (left).

Endoscopic biopsies from the stomach and duodenum indicated chronic granulomatous gastritis (Fig. 2). This finding was re-evaluated and confirmed by another pathologist.

Fig. 2.

(A, B) Liver biopsy. There are moderate chronic inflammatory cells in all portal areas with some caseating epithelioid granuloma, including Langhans multinucleated giant cells. Some extent of micro and macrovascular steatosis was seen. (C, D) Gastric mucosal biopsy. H&E-stained slides show oxyntic type mucosa with well-formed epithelioid granuloma and mild to moderate chronic inflammation. (E) Abdominal CT. Multiple hypodense hepatic nodules (left) and peripheral rim enhancement with IV contrast (right).

Abdominopelvic ultrasonography showed heterogeneous liver parenchymal echogenicity and multiple small, ill-defined hyperechoic areas in both liver lobes. Computed tomography (CT) of the chest, abdomen, and pelvis, performed after administering intravenous contrast material, exhibited multiple hypodense lesions with peripheral rim enhancement in the liver and clear lungs (Fig. 2).

Ultrasound-guided core needle biopsy of the liver lesions showed moderate chronic inflammatory cells in all portal areas, with some caseating epithelioid granulomas, including Langhans-type multinucleated giant cells, favoring Granulomatous Hepatitis (Fig. 2). The Tuberculin Skin Test (TST) and QuantiFERON TB (QFT) test were performed, and both were negative. The sputum smear and culture for acid-fast bacilli (AFB) were performed twice, and both were negative. According to the above findings, although diagnoses such as malignancy and sarcoidosis were suggested, our suspicion of primary gastrointestinal tuberculosis was high due to regional epidemiology and clinical features. Therefore, the patient was treated with anti-tuberculosis drugs in two phases. Two months of intensive treatment with rifampin, isoniazid, pyrazinamide, and ethambutol once daily, followed by four months of continuation treatment using rifampin and isoniazid.

Follow-up after four months showed an excellent response to this treatment; the patient's fatigue subsided, and the abdominal symptoms disappeared. Upper gastrointestinal endoscopy and abdominal ultrasonography performed 6 months later were unremarkable.

Discussion

Abdominal TB can develop at any age, it is most common in people between 25 and 45, and females account for a slight majority. Although the ileocecal region is the most commonly involved site in gastrointestinal tuberculosis, other locations may also be affected, emphasizing the heterogeneous presentation of this disease. In the present case, the involvement of the stomach, duodenum, and liver represents an uncommon pattern and highlights the need for heightened clinical awareness in atypical presentations.

Gastric tuberculosis is rare due to the bactericidal effect of gastric acid and rapid gastric emptying, and it is often associated with respiratory involvement. Direct mucosal infection, hematogenous spread, or extension from nearby tubercular lesions are the routes of infection [7]. Tuberculosis of the liver is also uncommon and mainly caused by systemic miliary tuberculosis. Furthermore, many cases reported in developed countries are in immunocompromised patients, primarily those with HIV infection. Our patient had no pulmonary involvement and was immunocompetent. Therefore, TB should be considered even in a person with clear lungs who has no history of immune deficiency.

Clinical manifestations of gastrointestinal and hepatic tuberculosis are highly variable and often overlap with other more common conditions. Abdominal pain is frequently the predominant symptom, as observed in our patient. Gastric involvement may mimic peptic ulcer disease, while more severe complications such as obstruction, perforation, bleeding, or mass-like lesions suggestive of malignancy have also been reported [8]. Tuberculosis in the liver can manifest as either a primary disease or a secondary infection originating from other focal TB sites. Most cases displayed non-specific symptoms, such as abdominal pain, fever, nocturnal diaphoresis, weight loss, hepatomegaly, epigastric pain, and jaundice, and are often misdiagnosed as liver cancer, liver abscess, benign tumor of the liver, and other mass lesions [9]. This particular medical condition may not present any discernible clinical symptoms. Still, more often, it is detected serendipitously during a diagnostic process aimed at identifying indistinct symptoms the patient displays. Two commercial tests are available for detecting Mycobacterium tuberculosis infection: the tuberculin skin test (TST) and the QuantiFERON-TB test (QFT). QFT is a simple blood test and is an interferon-gamma (IFN-γ) release assay, commonly known as an IGRA, and is a modern alternative to the TST (PPD, or Mantoux). Unlike the TST, QFT is unaffected by previous Bacillus Calmette-Guerin (BCG) vaccination [10]. QFT is particular and sensitive, but negative IGRA and tuberculin skin test non-reactivity cannot be used alone to exclude the diagnosis of active tuberculosis [11]. In our case, the TST and QFT were negative, and no acid-fast bacilli were detected in the sputum. TB is characterized by multiple lesions of varying densities on CT images, indicating multiple developmental stages. In this case study, parenchymal lesions showed both rim enhancements and poor enhancements [12]. Endoscopic biopsy yields poor results despite the presence of ulcers, and granulomas rarely appear due to their predominantly submucosal location. Fortunately, the pathologic sample of our patient exhibited evidence of granulomatous gastritis, and the diagnosis was made based on liver and gastric biopsies.

In conclusion, hepatic tuberculosis and gastroduodenal tuberculosis are usually associated with atypical and non-specific clinical manifestations and can be easily misdiagnosed. It is usually a diagnostic challenge and should be suspected in TB-endemic areas.

CRediT authorship contribution statement

Mojtaba Khademi Bafrooei: Writing – review & editing, Investigation, Data curation, Conceptualization. rahimi arash: Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Formal analysis, Data curation, Conceptualization. Ali Atashabparvar: Writing – review & editing, Validation, Resources, Methodology, Investigation. Narjes Seddighi: Writing – review & editing, Writing – original draft, Investigation.

Ethics approval and Consent to participate

This study was reviewed and approved by the Ethics Committee of the Hormozgan University of Medical Sciences (Ethics Code: IR.HUMS.REC.1401.177). Written informed consent for the publication of the article and any associated images was obtained from the patient.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Agreement

All authors were investigated the final and original draft of this manuscript and approved it.

Declaration of Competing Interest

The authors declare that they have no conflict of interest regarding the publication of this case report.

Appendix A. Supplementary material

Supplementary material