Fatal Isoniazid-Resistant Tuberculosis with Hepatic and Multiorgan Involvement in an HIV-Positive Patient

Fatal Isoniazid-Resistant Tuberculosis with Hepatic and Multiorgan Involvement in an HIV-Positive Patient | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Fatal Isoniazid-Resistant Tuberculosis with Hepatic and Multiorgan Involvement in an HIV-Positive Patient Sahak Mkrtchyan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7668432/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A fatal case of multiorgan isoniazid-resistant tuberculosis (TB) involving the liver, lungs, urinary tract, intestine, and central nervous system is presented in a 38-year-old male with advanced human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The patient presented with systemic symptoms including fever, dyspnea, and right upper quadrant discomfort. Isoniazid resistance was confirmed using GeneXpert and Xpert MTB/XDR assays across multiple specimens. Despite targeted anti-tuberculosis therapy and initiation of antiretroviral treatment, the patient developed respiratory failure and a tension pneumothorax, resulting in death seven weeks after admission. This case highlights the diagnostic and therapeutic challenges of disseminated drug-resistant TB in severely immunocompromised individuals. The rare hepatic involvement emphasizes the importance of considering extrapulmonary manifestations in HIV-associated TB. Early molecular diagnostics, prompt initiation of therapy, and vigilant monitoring for complications are critical to improving outcomes. Clinician awareness of such complex presentations is essential, particularly in regions with a high prevalence of drug-resistant TB. Infectious Diseases Tuberculosis Liver Tuberculosis HIV Introduction Although preventable and curable, tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, with thousands of deaths occurring each day [ 1 ]. People living with human immunodeficiency virus (HIV) are at significantly increased risk of developing active TB due to impaired cellular immunity [ 2 ]. The combined impact of these two diseases complicates both diagnosis and treatment, leading to worse patient outcomes and placing a substantial burden on healthcare systems globally [ 3 ]. In advanced HIV infection, TB often presents as disseminated disease involving multiple organs beyond the lungs, including the liver, central nervous system (CNS), and genitourinary tract. Despite its rarity, hepatic TB presents a diagnostic challenge due to its nonspecific clinical symptoms and imaging findings [ 4 ]. Patients with isoniazid-resistant TB are at higher risk of unfavorable treatment outcomes compared to those with drug-sensitive TB, particularly among older individuals and those receiving injectable agents [ 5 ]. While molecular diagnostics, such as GeneXpert and Xpert MTB/XDR, have improved the early identification of drug resistance, timely clinical recognition and initiation of therapy remain critical. In patients with coexisting HIV and drug-resistant TB, delays in diagnosis or treatment initiation can lead to rapid clinical decline and fatal outcomes. This report presents a fatal case of multiorgan isoniazid-resistant TB involving the liver, lungs, urinary tract, intestine, and CNS in a patient with advanced HIV and Acquired Immunodeficiency Syndrome (AIDS). This case illustrates the diagnostic and therapeutic complexity of disseminated drug-resistant TB in immunocompromised individuals and emphasizes the need for heightened vigilance for extrapulmonary involvement in high-risk patients. Case Presentation A 38-year-old male with no documented history of TB presented with a 30-day history of progressive general weakness, intermittent high-grade fever, dyspnea, profuse sweating, chills, and discomfort in the right upper quadrant. He also reported a headache and occasional spasmodic cough. The patient had not been previously treated with antiretroviral therapy (ART). Initial outpatient evaluation was unrevealing, and the patient was referred for further assessment. Imaging studies, including contrast-enhanced computed tomography and abdominal ultrasound, revealed a round hypoechoic lesion in the liver. A percutaneous aspiration biopsy of the hepatic lesion was performed, and a drainage catheter was placed. Microscopic examination of the aspirate demonstrated acid-fast bacilli (AFB 3+), and molecular testing via GeneXpert and Xpert MTB/XDR confirmed isoniazid resistance with retained sensitivity to fluoroquinolones, aminoglycosides, and pretomanid. The patient was subsequently transferred to a specialized TB center for further diagnostic evaluation and initiation of treatment. On admission to the Tuberculosis Control Center, the patient was conscious but intermittently responsive. He appeared pale and moderately ill, with drainage devices in place in the right hypochondrium. Vital signs were as follows: blood pressure 110/80 mmHg, heart rate 127 beats per minute, and oxygen saturation of 72% on room air. The patient’s previously reported symptoms persisted without significant improvement. Initial chest radiography demonstrated increased interstitial vascular markings and bilateral disseminated pulmonary lesions. An infiltrative opacity was noted in the right lower lung field, accompanied by a small right-sided pleural effusion. The hilar regions appeared infiltrated and were poorly visualized. Additionally, there was relaxation of the right hemidiaphragm and a single small radiopaque foreign body projected over the lower right lung field. Unfortunately, the original imaging studies are unavailable for inclusion in this report, as they were retained by forensic authorities following the patient’s death. Initial laboratory analysis revealed a reduced red blood cell count and hemoglobin level, consistent with anemia. White blood cell and platelet counts were within normal limits, while inflammatory markers were mildly elevated. Biochemical evaluation demonstrated hypoalbuminemia and elevated liver transaminases, suggesting hepatic involvement. Coagulation parameters remained within the normal range. These findings were consistent with systemic inflammation in the setting of disseminated TB and advanced immunosuppression. A summary of the laboratory results is provided in Table 1 . Table 1 Summary of Laboratory Findings Test Result Units Reference Range Complete Blood Count Red Blood Cells 3.02 ×10¹²/L 4.7–6.1 (men); 4.2–5.4 (women) Hemoglobin 82 g/L 135–175 (men); 120–160 (women) White Blood Cells 10.51 ×10⁹/L 4.0–10.0 Platelets 143 ×10⁹/L 150–400 Erythrocyte Sedimentation Rate 10 mm/hr < 20 Biochemistry Total Protein 74.8 g/L 64–83 Albumin 27.7 g/L 35–50 Urea 6.8 mmol/L 2.5–7.1 Creatinine 63 µmol/L 60–110 Alanine Aminotransferase 27.8 U/L < 40 Aspartate Aminotransferase 76.5 U/L < 40 Total Bilirubin 13.3 µmol/L 5–21 Magnesium 0.74 mmol/L 0.7–1.1 Coagulation Profile Prothrombin Time 14.1 sec 11–15 Fibrinogen 3.3 g/L 2.0–4.0 Thrombin Time 18.4 sec 14–21 Activated Partial Thromboplastin Time 35.4 sec 25–35 International Normalized Ratio 1.1 0.9–1.1 Prothrombin Index 86.5 % 70–120 Further investigations confirmed HIV infection, with a viral load of 30,000 copies/mL and a CD4 + T-cell count of < 200 cells/mm³, indicating advanced immunosuppression. The patient was diagnosed with disseminated isoniazid-resistant TB involving multiple organ systems. Isoniazid-resistant, AFB-positive Mycobacterium tuberculosis was identified in both liver aspirate and urine samples. Although sputum smear microscopy was negative, culture confirmed AFB growth with isoniazid resistance. CNS involvement was supported by cerebrospinal fluid GeneXpert testing, which also revealed isoniazid resistance. Polymerase chain reaction detected co-infection with Epstein-Barr virus and cytomegalovirus. Urinary lipoarabinomannan testing was positive. On hospital day 30, Pneumocystis jirovecii was identified in sputum, further indicating profound immunodeficiency. A reactive rapid plasma reagin test (titer: 1:4) raised suspicion for concurrent syphilis. Abdominal ultrasound revealed hepatomegaly (up to 22.8 cm), splenomegaly (20.4 × 7.4 cm), sonographic features consistent with cholangitis, and cystic lesions suggestive of hepatic tuberculosis in segments VI and VII, one of which had been previously drained. Minimal ascites and bilateral minimal pleural effusions were also noted. No evidence of biliary or portal hypertension was observed. Repeat ultrasound during the second week of admission showed minimal improvement in hepatosplenomegaly and resolution of ascites. Echocardiography on admission revealed borderline right atrial enlargement, mild pulmonary hypertension with an estimated pulmonary artery pressure of 33–34 mmHg, and moderate biventricular function with an ejection fraction of 46–47%. A circumferential pericardial effusion measuring approximately 160 mL was also noted and remained stable throughout the hospitalization. The patient was initiated on a second-line anti-tuberculosis regimen consisting of rifampin, pyrazinamide, ethambutol, and levofloxacin due to concerns about drug resistance and the disseminated nature of the disease. One week later, cycloserine and clofazimine were added to broaden antimicrobial coverage and address the case's complexity. Concurrently, the patient received prophylactic co-trimoxazole to prevent Pneumocystis jirovecii pneumonia, along with supportive care and oxygen supplementation for respiratory compromise. Given the patient’s underlying HIV infection and immunocompromised status, ART was initiated on day 14 of hospitalization with tenofovir, lamivudine, and dolutegravir. Valganciclovir was started the following day in response to confirmed CNS cytomegalovirus infection. Despite the initiation of comprehensive antimicrobial and supportive therapies, the patient’s clinical condition continued to deteriorate. By day 18 of hospitalization, he showed signs of progressive respiratory failure, including worsening hypoxia, with oxygen saturation dropping to 79% despite high-flow oxygen therapy at 10 liters per minute via face mask. Given the severity of his respiratory compromise and the risk of imminent decompensation, he was urgently transferred to the intensive care unit for closer monitoring and advanced respiratory support. Subsequent diagnostic evaluations revealed ongoing systemic involvement and hemodynamic stress. Transthoracic echocardiography demonstrated sinus tachycardia and progression of tricuspid regurgitation to grade II-III, along with more than 50% collapse of the inferior vena cava-findings consistent with volume depletion or elevated intrathoracic pressure. The pericardial effusion remained stable at approximately 70 mL. Follow-up abdominal ultrasound on day 42 demonstrated minimal changes compared to prior imaging. Marked lipodystrophy and cholangitis persisted, with no evidence of portal or biliary hypertension. The kidneys showed preserved corticomedullary differentiation without signs of flow obstruction. Ascites was absent; however, meteorism and periportal lymphadenopathy were noted, along with minimal bilateral maxillary sinus fluid. Laboratory results obtained on day 47 of hospitalization are summarized in Table 2 . Table 2 Laboratory Results on Day 47 of Hospitalization Test Result Unit Reference Range Complete Blood Count Red Blood Cells 2.78 ×10¹²/L 4.5–5.9 (men) 4.1–5.1 (women) Hemoglobin 85 g/L 130–170 (men) 120–150 (women) White Blood Cells 3.41 ×10⁹/L 4.0–11.0 Platelets 176 ×10⁹/L 150–400 Erythrocyte Sedimentation Rate 79 mm/hr 0–20 (men) 0–30 (women) Biochemistry Total Protein 61.9 g/L 60–80 Albumin 22.9 g/L 35–50 Urea 3.5 mmol/L 2.5–7.5 Creatinine 47 µmol/L 62–106 (men) 44–80 (women) Alanine Aminotransferase 10.8 U/L 7–56 Aspartate Aminotransferase 31.3 U/L 10–40 Coagulation Profile Prothrombin Time 14.5 sec 11–15 Fibrinogen 3.65 g/L 2.0–4.0 Thrombin Time 20 sec 14–21 Activated Partial Thromboplastin Time 26.5 sec 25–35 International Normalized Ratio 1.21 0.8–1.2 Index of Prothrombin 79.2 % 70–130 Chest imaging on day 49 revealed partial resorption of prior pulmonary infiltrates and lesions. However, a dramatic deterioration occurred the following day, with complete collapse of the left lung and a mediastinal shift toward the right, consistent with a spontaneous tension pneumothorax. On day 50 of hospitalization, the patient experienced a sudden cardiovascular collapse. At approximately 11:10, bradycardia rapidly progressed to asystole. Blood pressure and oxygen saturation became unmeasurable. Immediate advanced cardiopulmonary resuscitation was initiated and continued for approximately 30 minutes. Despite aggressive resuscitative efforts, there was no return of spontaneous circulation, and the patient was pronounced dead. The final diagnosis was acute respiratory failure secondary to disseminated isoniazid-resistant tuberculosis involving the lungs, liver, urinary tract, intestines, and central nervous system, complicated by Epstein-Barr virus co-infection, cytomegalovirus CNS co-infection, Pneumocystis pneumonia, stage IV HIV/AIDS with severe immunodeficiency, spontaneous tension pneumothorax, and anemia with pancytopenia. Discussion Hepatic TB is an uncommon yet critical manifestation of extrapulmonary TB, particularly among patients with HIV infection and severe immunosuppression (CD4 < 200). In such individuals, hepatic involvement typically occurs as part of disseminated TB rather than as an isolated lesion [ 6 ]. In this case, the patient’s profound immunosuppression (CD4 count < 200 and an HIV viral load of 30,000 copies/mL) was consistent with the typical risk profile for miliary hepatic TB. Clinically, hepatic TB often presents with nonspecific features such as hepatomegaly, fever, right upper quadrant pain, elevated alkaline phosphatase, gamma-glutamyl transferase, hypoalbuminemia, and mild transaminase elevation [ 7 ]. In this case, several of these findings were observed, including hepatomegaly, cholangitis, hypoalbuminemia, and elevated aspartate aminotransferase. These clinical and laboratory abnormalities, although nonspecific, were consistent with disseminated hepatic involvement and highlighted the diagnostic complexity in immunocompromised patients with advanced HIV. Identification of hepatic TB required a high index of suspicion due to the patient’s immunocompromised state and residence in a TB-endemic region. Imaging via ultrasound revealed hypoechoic lesions in the liver, which are known to be nonspecific and may mimic hepatic abscesses or malignancies [ 8 ]. To clarify the etiology, percutaneous aspiration was performed, and smear microscopy demonstrated acid-fast bacilli. Confirmation was subsequently obtained through molecular testing using GeneXpert and Xpert MTB/XDR, which detected Mycobacterium tuberculosis and confirmed isoniazid resistance. This case highlights the diagnostic complexity of hepatic TB, particularly in HIV-positive patients, and emphasizes the importance of integrating clinical suspicion with imaging, image-guided biopsy, and microbiologic and molecular diagnostics [ 9 ], even when histopathological analysis is not available. Isoniazid monoresistance complicated the use of the standard four-drug TB regimen by diminishing early bactericidal activity, which is critical during the initiation phase of treatment [ 10 ]. According to WHO guidelines, treatment duration should be extended and supplemented with additional agents such as fluoroquinolones [ 11 ]. The patient was initially treated with rifampicin, pyrazinamide, ethambutol, and levofloxacin, with cycloserine and clofazimine added subsequently. In cases of HIV/TB coinfection, early initiation of ART within 2–8 weeks of starting anti-TB treatment has been shown to significantly reduce mortality [ 12 ]. ART was initiated on day 14 in this case, aligning with established best practices. Despite adherence to guideline-directed therapy, disseminated and drug-resistant TB in immunocompromised individuals remains associated with high mortality. A study from South Africa reported high mortality rates in HIV-positive patients with hepatic TB, even under standard treatment [ 13 ]. In this patient, extensive multiorgan involvement and the presence of additional opportunistic infections-such as cytomegalovirus, Pneumocystis jirovecii pneumonia, and complications like tension pneumothorax-likely contributed to the fatal outcome. Conclusions This case highlights the deadly nature of disseminated isoniazid-resistant tuberculosis in advanced HIV/AIDS. Hepatic involvement, often subtle, signals systemic spread and complicates diagnosis and treatment. Clinicians should suspect hepatic TB in HIV patients with liver lesions and confirm with biopsy and molecular testing. Rapid drug-resistance diagnostics enable timely, tailored therapy. Management must include second-line TB drugs, early ART, and close monitoring for opportunistic infections and complications. Despite appropriate treatment, mortality remains high in patients with severe immunosuppression and multiorgan disease. This case reinforces the importance of early recognition, multidisciplinary care, and the need to suspect extrapulmonary TB in high-risk patients, even in the absence of classic symptoms. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written or verbal informed consent was obtained from the patient for publication of this case report. Availability of data and materials Not applicable. Competing interests The author declare that they have no competing interests. Funding No external funding was received for this study. Authors’ contributions Sahak Mkrtchyan was responsible for the conception, drafting, and approval of the final manuscript. References Global TB, Epidemic (2025) Accessed: July 24, 2025: https://www.cdc.gov/global-hiv-tb/php/globaltb/index.html TB Risk and People with HIV (2025) Accessed: July 24, 2025: https://www.cdc.gov/tb/risk-factors/hiv.html Patel A, Pundkar A, Agarwal A et al (2024) A Comprehensive Review of HIV-Associated Tuberculosis: Clinical Challenges and Advances in Management. Cureus 16:9. 10.7759/cureus.68784 Ch'ng LS, Amzar H, Ghazali KC et al (2018) Imaging appearances of hepatic tuberculosis: experience with 12 patients. Clin Radiol 73:321e11. 10.1016/j.crad.2017.10.016 Xiao W, Chen J, Rao L et al (2025) Treatment outcomes and key factors contributing to unfavourable outcomes among isoniazid-resistant pulmonary tuberculosis patients in Shanghai, China. J Glob Antimicrob Resist 42:177–186. 10.1016/j.jgar.2025.02.003 Amarapurkar DN, Patel ND, Amarapurkar AD (2008) Hepatobiliary tuberculosis in western India. Indian J Pathol Microbiol 52:175–181. 10.4103/0377-4929.41644 Hickey AJ, Gounder L, Moosa MYS et al (2015) A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection. BMC Infect Dis 15:209. 10.1186/s12879-015-0944-6 Sharma V, Ahuja V (2025) Hepatic tuberculosis. Treatment and Management of Tropical Liver Disease. Debes J (ed): Elsevier B.V., Amsterdam, Netherlands; 104–110. 10.1016/B978-0-323-87031-3.00022 – 6 Wu Z, Wang WL, Zhu Y et al (2013) Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. Int J Clin Exp Med 6:845–850 Padda IS, Reddy KM (2025) Antitubercular Medications. StatPearls (Internet). StatPearls Publishing, Treasure Island, Florida (FL), USA World Health Organization (2018) WHO Treatment Guidelines for Isoniazid-Resistant Tuberculosis: Supplement to the WHO Treatment Guidelines for Drug-Resistant Tuberculosis. World Health Organization, Geneva. https://www.ncbi.nlm.nih.gov/books/NBK531418/ Tuberculosis/HIV Coinfection (2024) Accessed: July 25, 2025: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tuberculosishiv-coinfection Gounder L, Moodley P, Drain PK et al (2017) Hepatic tuberculosis in human immunodeficiency virus co-infected adults: a case series of South African adults. BMC Infect Dis 17:115. 10.1186/s12879-017-2222-2 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7668432","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":518343172,"identity":"023baab3-b784-44da-a9bb-93919b3318e9","order_by":0,"name":"Sahak Mkrtchyan","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0004-3157-5285","institution":"Department of Tuberculosis, Yerevan State Medical University after Mkhitar Heratsi","correspondingAuthor":true,"prefix":"","firstName":"Sahak","middleName":"","lastName":"Mkrtchyan","suffix":""}],"badges":[],"createdAt":"2025-09-21 20:01:27","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7668432/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7668432/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91985060,"identity":"92a9d491-05bf-489a-a4cd-c122f0b45da7","added_by":"auto","created_at":"2025-09-23 11:48:39","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29247,"visible":true,"origin":"","legend":"","description":"","filename":"Researchsquare.docx","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/ed8b8f5e9af7189a5ffb9bae.docx"},{"id":91985054,"identity":"5cc166d5-7f0a-44e1-b020-c8a521fc017c","added_by":"auto","created_at":"2025-09-23 11:48:39","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs7668432.json","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/0af0c26a7c2b81661cddc10d.json"},{"id":91985045,"identity":"94399794-ecaa-4532-bc23-f8334f1e6ff4","added_by":"auto","created_at":"2025-09-23 11:48:38","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48226,"visible":true,"origin":"","legend":"","description":"","filename":"rs76684320enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/91ae6b0c8a685378ab25d623.xml"},{"id":91985053,"identity":"920cec79-abcc-4263-8b33-cd08b57a7a05","added_by":"auto","created_at":"2025-09-23 11:48:39","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":46711,"visible":true,"origin":"","legend":"","description":"","filename":"rs76684320structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/a894307101cf77a17501a1da.xml"},{"id":91985033,"identity":"9fb8d60a-0f3a-4144-801e-7e41cc054711","added_by":"auto","created_at":"2025-09-23 11:48:37","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":50720,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/8d370808d709b412149a6a6b.html"},{"id":91985074,"identity":"9b75f4f7-b9ce-4630-b104-c5d96e9ea8d8","added_by":"auto","created_at":"2025-09-23 11:48:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":378320,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7668432/v1/a22b00f6-5fb5-4dd2-8c1b-96fe0b367303.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eFatal Isoniazid-Resistant Tuberculosis with Hepatic and Multiorgan Involvement in an HIV-Positive Patient\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAlthough preventable and curable, tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, with thousands of deaths occurring each day [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. People living with human immunodeficiency virus (HIV) are at significantly increased risk of developing active TB due to impaired cellular immunity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The combined impact of these two diseases complicates both diagnosis and treatment, leading to worse patient outcomes and placing a substantial burden on healthcare systems globally [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In advanced HIV infection, TB often presents as disseminated disease involving multiple organs beyond the lungs, including the liver, central nervous system (CNS), and genitourinary tract. Despite its rarity, hepatic TB presents a diagnostic challenge due to its nonspecific clinical symptoms and imaging findings [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePatients with isoniazid-resistant TB are at higher risk of unfavorable treatment outcomes compared to those with drug-sensitive TB, particularly among older individuals and those receiving injectable agents [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While molecular diagnostics, such as GeneXpert and Xpert MTB/XDR, have improved the early identification of drug resistance, timely clinical recognition and initiation of therapy remain critical. In patients with coexisting HIV and drug-resistant TB, delays in diagnosis or treatment initiation can lead to rapid clinical decline and fatal outcomes.\u003c/p\u003e\u003cp\u003eThis report presents a fatal case of multiorgan isoniazid-resistant TB involving the liver, lungs, urinary tract, intestine, and CNS in a patient with advanced HIV and Acquired Immunodeficiency Syndrome (AIDS). This case illustrates the diagnostic and therapeutic complexity of disseminated drug-resistant TB in immunocompromised individuals and emphasizes the need for heightened vigilance for extrapulmonary involvement in high-risk patients.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 38-year-old male with no documented history of TB presented with a 30-day history of progressive general weakness, intermittent high-grade fever, dyspnea, profuse sweating, chills, and discomfort in the right upper quadrant. He also reported a headache and occasional spasmodic cough. The patient had not been previously treated with antiretroviral therapy (ART).\u003c/p\u003e\u003cp\u003eInitial outpatient evaluation was unrevealing, and the patient was referred for further assessment. Imaging studies, including contrast-enhanced computed tomography and abdominal ultrasound, revealed a round hypoechoic lesion in the liver. A percutaneous aspiration biopsy of the hepatic lesion was performed, and a drainage catheter was placed. Microscopic examination of the aspirate demonstrated acid-fast bacilli (AFB 3+), and molecular testing via GeneXpert and Xpert MTB/XDR confirmed isoniazid resistance with retained sensitivity to fluoroquinolones, aminoglycosides, and pretomanid. The patient was subsequently transferred to a specialized TB center for further diagnostic evaluation and initiation of treatment.\u003c/p\u003e\u003cp\u003eOn admission to the Tuberculosis Control Center, the patient was conscious but intermittently responsive. He appeared pale and moderately ill, with drainage devices in place in the right hypochondrium. Vital signs were as follows: blood pressure 110/80 mmHg, heart rate 127 beats per minute, and oxygen saturation of 72% on room air. The patient\u0026rsquo;s previously reported symptoms persisted without significant improvement.\u003c/p\u003e\u003cp\u003eInitial chest radiography demonstrated increased interstitial vascular markings and bilateral disseminated pulmonary lesions. An infiltrative opacity was noted in the right lower lung field, accompanied by a small right-sided pleural effusion. The hilar regions appeared infiltrated and were poorly visualized. Additionally, there was relaxation of the right hemidiaphragm and a single small radiopaque foreign body projected over the lower right lung field. Unfortunately, the original imaging studies are unavailable for inclusion in this report, as they were retained by forensic authorities following the patient\u0026rsquo;s death.\u003c/p\u003e\u003cp\u003eInitial laboratory analysis revealed a reduced red blood cell count and hemoglobin level, consistent with anemia. White blood cell and platelet counts were within normal limits, while inflammatory markers were mildly elevated. Biochemical evaluation demonstrated hypoalbuminemia and elevated liver transaminases, suggesting hepatic involvement. Coagulation parameters remained within the normal range. These findings were consistent with systemic inflammation in the setting of disseminated TB and advanced immunosuppression. A summary of the laboratory results is provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of Laboratory Findings\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTest\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResult\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnits\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReference Range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete Blood Count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRed Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10\u0026sup1;\u0026sup2;/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.7\u0026ndash;6.1 (men); 4.2\u0026ndash;5.4 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e135\u0026ndash;175 (men); 120\u0026ndash;160 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.0\u0026ndash;10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e150\u0026ndash;400\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythrocyte Sedimentation Rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emm/hr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiochemistry\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64\u0026ndash;83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35\u0026ndash;50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5\u0026ndash;7.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026micro;mol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60\u0026ndash;110\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlanine Aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspartate Aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026micro;mol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5\u0026ndash;21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u0026ndash;1.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoagulation Profile\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProthrombin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u0026ndash;15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026ndash;4.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u0026ndash;21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eActivated Partial Thromboplastin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25\u0026ndash;35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternational Normalized Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.9\u0026ndash;1.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProthrombin Index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e86.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70\u0026ndash;120\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFurther investigations confirmed HIV infection, with a viral load of 30,000 copies/mL and a CD4\u0026thinsp;+\u0026thinsp;T-cell count of \u0026lt;\u0026thinsp;200 cells/mm\u0026sup3;, indicating advanced immunosuppression. The patient was diagnosed with disseminated isoniazid-resistant TB involving multiple organ systems. Isoniazid-resistant, AFB-positive \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e was identified in both liver aspirate and urine samples. Although sputum smear microscopy was negative, culture confirmed AFB growth with isoniazid resistance. CNS involvement was supported by cerebrospinal fluid GeneXpert testing, which also revealed isoniazid resistance. Polymerase chain reaction detected co-infection with Epstein-Barr virus and cytomegalovirus. Urinary lipoarabinomannan testing was positive. On hospital day 30, \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e was identified in sputum, further indicating profound immunodeficiency. A reactive rapid plasma reagin test (titer: 1:4) raised suspicion for concurrent syphilis.\u003c/p\u003e\u003cp\u003eAbdominal ultrasound revealed hepatomegaly (up to 22.8 cm), splenomegaly (20.4 \u0026times; 7.4 cm), sonographic features consistent with cholangitis, and cystic lesions suggestive of hepatic tuberculosis in segments VI and VII, one of which had been previously drained. Minimal ascites and bilateral minimal pleural effusions were also noted. No evidence of biliary or portal hypertension was observed. Repeat ultrasound during the second week of admission showed minimal improvement in hepatosplenomegaly and resolution of ascites.\u003c/p\u003e\u003cp\u003eEchocardiography on admission revealed borderline right atrial enlargement, mild pulmonary hypertension with an estimated pulmonary artery pressure of 33\u0026ndash;34 mmHg, and moderate biventricular function with an ejection fraction of 46\u0026ndash;47%. A circumferential pericardial effusion measuring approximately 160 mL was also noted and remained stable throughout the hospitalization.\u003c/p\u003e\u003cp\u003eThe patient was initiated on a second-line anti-tuberculosis regimen consisting of rifampin, pyrazinamide, ethambutol, and levofloxacin due to concerns about drug resistance and the disseminated nature of the disease. One week later, cycloserine and clofazimine were added to broaden antimicrobial coverage and address the case's complexity. Concurrently, the patient received prophylactic co-trimoxazole to prevent \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia, along with supportive care and oxygen supplementation for respiratory compromise.\u003c/p\u003e\u003cp\u003eGiven the patient\u0026rsquo;s underlying HIV infection and immunocompromised status, ART was initiated on day 14 of hospitalization with tenofovir, lamivudine, and dolutegravir. Valganciclovir was started the following day in response to confirmed CNS cytomegalovirus infection.\u003c/p\u003e\u003cp\u003eDespite the initiation of comprehensive antimicrobial and supportive therapies, the patient\u0026rsquo;s clinical condition continued to deteriorate. By day 18 of hospitalization, he showed signs of progressive respiratory failure, including worsening hypoxia, with oxygen saturation dropping to 79% despite high-flow oxygen therapy at 10 liters per minute via face mask. Given the severity of his respiratory compromise and the risk of imminent decompensation, he was urgently transferred to the intensive care unit for closer monitoring and advanced respiratory support.\u003c/p\u003e\u003cp\u003eSubsequent diagnostic evaluations revealed ongoing systemic involvement and hemodynamic stress. Transthoracic echocardiography demonstrated sinus tachycardia and progression of tricuspid regurgitation to grade II-III, along with more than 50% collapse of the inferior vena cava-findings consistent with volume depletion or elevated intrathoracic pressure. The pericardial effusion remained stable at approximately 70 mL.\u003c/p\u003e\u003cp\u003eFollow-up abdominal ultrasound on day 42 demonstrated minimal changes compared to prior imaging. Marked lipodystrophy and cholangitis persisted, with no evidence of portal or biliary hypertension. The kidneys showed preserved corticomedullary differentiation without signs of flow obstruction. Ascites was absent; however, meteorism and periportal lymphadenopathy were noted, along with minimal bilateral maxillary sinus fluid. Laboratory results obtained on day 47 of hospitalization are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLaboratory Results on Day 47 of Hospitalization\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTest\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResult\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnit\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReference Range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete Blood Count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRed Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10\u0026sup1;\u0026sup2;/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.5\u0026ndash;5.9 (men) 4.1\u0026ndash;5.1 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e130\u0026ndash;170 (men) 120\u0026ndash;150 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.0\u0026ndash;11.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026times;10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e150\u0026ndash;400\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythrocyte Sedimentation Rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emm/hr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u0026ndash;20 (men) 0\u0026ndash;30 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiochemistry\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60\u0026ndash;80\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35\u0026ndash;50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5\u0026ndash;7.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026micro;mol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62\u0026ndash;106 (men) 44\u0026ndash;80 (women)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlanine Aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7\u0026ndash;56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspartate Aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10\u0026ndash;40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoagulation Profile\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProthrombin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u0026ndash;15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u0026ndash;4.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u0026ndash;21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eActivated Partial Thromboplastin Time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25\u0026ndash;35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternational Normalized Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.8\u0026ndash;1.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex of Prothrombin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70\u0026ndash;130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eChest imaging on day 49 revealed partial resorption of prior pulmonary infiltrates and lesions. However, a dramatic deterioration occurred the following day, with complete collapse of the left lung and a mediastinal shift toward the right, consistent with a spontaneous tension pneumothorax.\u003c/p\u003e\u003cp\u003eOn day 50 of hospitalization, the patient experienced a sudden cardiovascular collapse. At approximately 11:10, bradycardia rapidly progressed to asystole. Blood pressure and oxygen saturation became unmeasurable. Immediate advanced cardiopulmonary resuscitation was initiated and continued for approximately 30 minutes. Despite aggressive resuscitative efforts, there was no return of spontaneous circulation, and the patient was pronounced dead.\u003c/p\u003e\u003cp\u003eThe final diagnosis was acute respiratory failure secondary to disseminated isoniazid-resistant tuberculosis involving the lungs, liver, urinary tract, intestines, and central nervous system, complicated by Epstein-Barr virus co-infection, cytomegalovirus CNS co-infection, Pneumocystis pneumonia, stage IV HIV/AIDS with severe immunodeficiency, spontaneous tension pneumothorax, and anemia with pancytopenia.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHepatic TB is an uncommon yet critical manifestation of extrapulmonary TB, particularly among patients with HIV infection and severe immunosuppression (CD4\u0026thinsp;\u0026lt;\u0026thinsp;200). In such individuals, hepatic involvement typically occurs as part of disseminated TB rather than as an isolated lesion [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this case, the patient\u0026rsquo;s profound immunosuppression (CD4 count\u0026thinsp;\u0026lt;\u0026thinsp;200 and an HIV viral load of 30,000 copies/mL) was consistent with the typical risk profile for miliary hepatic TB.\u003c/p\u003e\u003cp\u003eClinically, hepatic TB often presents with nonspecific features such as hepatomegaly, fever, right upper quadrant pain, elevated alkaline phosphatase, gamma-glutamyl transferase, hypoalbuminemia, and mild transaminase elevation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this case, several of these findings were observed, including hepatomegaly, cholangitis, hypoalbuminemia, and elevated aspartate aminotransferase. These clinical and laboratory abnormalities, although nonspecific, were consistent with disseminated hepatic involvement and highlighted the diagnostic complexity in immunocompromised patients with advanced HIV.\u003c/p\u003e\u003cp\u003eIdentification of hepatic TB required a high index of suspicion due to the patient\u0026rsquo;s immunocompromised state and residence in a TB-endemic region. Imaging via ultrasound revealed hypoechoic lesions in the liver, which are known to be nonspecific and may mimic hepatic abscesses or malignancies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. To clarify the etiology, percutaneous aspiration was performed, and smear microscopy demonstrated acid-fast bacilli. Confirmation was subsequently obtained through molecular testing using GeneXpert and Xpert MTB/XDR, which detected \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e and confirmed isoniazid resistance. This case highlights the diagnostic complexity of hepatic TB, particularly in HIV-positive patients, and emphasizes the importance of integrating clinical suspicion with imaging, image-guided biopsy, and microbiologic and molecular diagnostics [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], even when histopathological analysis is not available.\u003c/p\u003e\u003cp\u003eIsoniazid monoresistance complicated the use of the standard four-drug TB regimen by diminishing early bactericidal activity, which is critical during the initiation phase of treatment [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. According to WHO guidelines, treatment duration should be extended and supplemented with additional agents such as fluoroquinolones [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The patient was initially treated with rifampicin, pyrazinamide, ethambutol, and levofloxacin, with cycloserine and clofazimine added subsequently. In cases of HIV/TB coinfection, early initiation of ART within 2\u0026ndash;8 weeks of starting anti-TB treatment has been shown to significantly reduce mortality [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. ART was initiated on day 14 in this case, aligning with established best practices.\u003c/p\u003e\u003cp\u003e Despite adherence to guideline-directed therapy, disseminated and drug-resistant TB in immunocompromised individuals remains associated with high mortality. A study from South Africa reported high mortality rates in HIV-positive patients with hepatic TB, even under standard treatment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this patient, extensive multiorgan involvement and the presence of additional opportunistic infections-such as cytomegalovirus, \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia, and complications like tension pneumothorax-likely contributed to the fatal outcome.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case highlights the deadly nature of disseminated isoniazid-resistant tuberculosis in advanced HIV/AIDS. Hepatic involvement, often subtle, signals systemic spread and complicates diagnosis and treatment. Clinicians should suspect hepatic TB in HIV patients with liver lesions and confirm with biopsy and molecular testing. Rapid drug-resistance diagnostics enable timely, tailored therapy. Management must include second-line TB drugs, early ART, and close monitoring for opportunistic infections and complications. Despite appropriate treatment, mortality remains high in patients with severe immunosuppression and multiorgan disease. This case reinforces the importance of early recognition, multidisciplinary care, and the need to suspect extrapulmonary TB in high-risk patients, even in the absence of classic symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten or verbal informed consent was obtained from the patient for publication of this case report.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe author declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eSahak Mkrtchyan was responsible for the conception, drafting, and approval of the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal TB, Epidemic (2025) Accessed: July 24, 2025: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/global-hiv-tb/php/globaltb/index.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/global-hiv-tb/php/globaltb/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTB Risk and People with HIV (2025) Accessed: July 24, 2025: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/tb/risk-factors/hiv.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/tb/risk-factors/hiv.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatel A, Pundkar A, Agarwal A et al (2024) A Comprehensive Review of HIV-Associated Tuberculosis: Clinical Challenges and Advances in Management. Cureus 16:9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.68784\u003c/span\u003e\u003cspan address=\"10.7759/cureus.68784\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCh'ng LS, Amzar H, Ghazali KC et al (2018) Imaging appearances of hepatic tuberculosis: experience with 12 patients. Clin Radiol 73:321e11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.crad.2017.10.016\u003c/span\u003e\u003cspan address=\"10.1016/j.crad.2017.10.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXiao W, Chen J, Rao L et al (2025) Treatment outcomes and key factors contributing to unfavourable outcomes among isoniazid-resistant pulmonary tuberculosis patients in Shanghai, China. J Glob Antimicrob Resist 42:177\u0026ndash;186. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jgar.2025.02.003\u003c/span\u003e\u003cspan address=\"10.1016/j.jgar.2025.02.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmarapurkar DN, Patel ND, Amarapurkar AD (2008) Hepatobiliary tuberculosis in western India. Indian J Pathol Microbiol 52:175\u0026ndash;181. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0377-4929.41644\u003c/span\u003e\u003cspan address=\"10.4103/0377-4929.41644\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHickey AJ, Gounder L, Moosa MYS et al (2015) A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection. BMC Infect Dis 15:209. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12879-015-0944-6\u003c/span\u003e\u003cspan address=\"10.1186/s12879-015-0944-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSharma V, Ahuja V (2025) Hepatic tuberculosis. Treatment and Management of Tropical Liver Disease. Debes J (ed): Elsevier B.V., Amsterdam, Netherlands; 104\u0026ndash;110. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/B978-0-323-87031-3.00022\u0026thinsp;\u0026ndash;\u0026thinsp;6\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-323-87031-3.00022\u0026thinsp;\u0026ndash;\u0026thinsp;6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu Z, Wang WL, Zhu Y et al (2013) Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. Int J Clin Exp Med 6:845\u0026ndash;850\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePadda IS, Reddy KM (2025) Antitubercular Medications. StatPearls (Internet). StatPearls Publishing, Treasure Island, Florida (FL), USA\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization (2018) WHO Treatment Guidelines for Isoniazid-Resistant Tuberculosis: Supplement to the WHO Treatment Guidelines for Drug-Resistant Tuberculosis. World Health Organization, Geneva. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK531418/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK531418/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTuberculosis/HIV Coinfection (2024) Accessed: July 25, 2025: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tuberculosishiv-coinfection\u003c/span\u003e\u003cspan address=\"https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tuberculosishiv-coinfection\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGounder L, Moodley P, Drain PK et al (2017) Hepatic tuberculosis in human immunodeficiency virus co-infected adults: a case series of South African adults. BMC Infect Dis 17:115. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12879-017-2222-2\u003c/span\u003e\u003cspan address=\"10.1186/s12879-017-2222-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tuberculosis, Liver Tuberculosis, HIV","lastPublishedDoi":"10.21203/rs.3.rs-7668432/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7668432/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA fatal case of multiorgan isoniazid-resistant tuberculosis (TB) involving the liver, lungs, urinary tract, intestine, and central nervous system is presented in a 38-year-old male with advanced human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The patient presented with systemic symptoms including fever, dyspnea, and right upper quadrant discomfort. Isoniazid resistance was confirmed using GeneXpert and Xpert MTB/XDR assays across multiple specimens. Despite targeted anti-tuberculosis therapy and initiation of antiretroviral treatment, the patient developed respiratory failure and a tension pneumothorax, resulting in death seven weeks after admission. This case highlights the diagnostic and therapeutic challenges of disseminated drug-resistant TB in severely immunocompromised individuals. The rare hepatic involvement emphasizes the importance of considering extrapulmonary manifestations in HIV-associated TB. Early molecular diagnostics, prompt initiation of therapy, and vigilant monitoring for complications are critical to improving outcomes. Clinician awareness of such complex presentations is essential, particularly in regions with a high prevalence of drug-resistant TB.\u003c/p\u003e","manuscriptTitle":"Fatal Isoniazid-Resistant Tuberculosis with Hepatic and Multiorgan Involvement in an HIV-Positive Patient","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-23 11:48:12","doi":"10.21203/rs.3.rs-7668432/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"224f76cf-2195-4e4b-8f09-07bbf0c6c334","owner":[],"postedDate":"September 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55191366,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2025-09-23T11:48:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-23 11:48:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7668432","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7668432","identity":"rs-7668432","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}