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Pulmonary tuberculosis combined with hepatic tuberculosis: a case report and literature review1 Jiang-Rong Liao1M.D, Dan Zhang1M.D, Xue-Ling Wu2 M.D, Ph.D. 1. Institute of Respiratory Medicine,Guizhou Aerospace Hospital, Zunyi, 563000, Guizhou Province, P. R. China

2. Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China

Corresponding author: Xueling Wu, Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 China. Email: [email protected] Short Title: Pulmonary and hepatic tuberculosis Conflict of Interest Statement: The authors have no conflicting financial interests.

Source of Funding Statement: Financially supported by the National Natural Science Foundation of China 81270130 and 81070056 (X.L. Wu).

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/crj.12167 This article is protected by copyright. All rights reserved. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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ABSTRACT Background: Tuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis, may invade all organs but mainly affect lungs. Most hepatic tuberculosis

could be a part of systemic miliary tuberculosis. Methods: We reported a case of pulmonary tuberculosis combined with hepatic tuberculosis and reviewed the relevant literature. Results: A 40-year-old Chinese male with fatigue for half a year and cough as well as night sweat for 2 months was admitted to our ospital. The chest CT showed multiple nodules combined with bronchial stenosis and lymphadenectasis in the mediastina at the right hilum of lung. The epigastrium CT showed lumps in the liver and retroperitoneal lymphadenectasis in the peritoneal cavity. The abdominal color Doppler ultrasound revealed lumps in the liver. The lung and liver puncture biopsy

revealed granulomatous lesions, chronic inflammatory changes in the strip-like fibrous tissues and plenty of caseification, all of which suggest the diagnosis of tuberculosis. Conclusion: Hepatic tuberculosis is usually associated with atypical clinical manifestations. Imageological examination combined with imaging-guided fine needle aspiration biopsy may be the best method for the confirmed diagnosis. Keywords: pulmonary tuberculosis; hepatic tuberculosis; case report

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INTRODUCTION Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis and Tubercle bacillus. Tuberculosis may invade all organs but mainly affect lungs. Hepatic tuberculosis is relatively rare, and hence the clinical misdiagnosis rate and mistherapy rate are high due to lack of specific symptoms and signs.

Most hepatic tuberculosis belong to the category of systemic military tuberculosis. The main clinical manifestations are extrahepatic, secondary to pulmonary tuberculosis and intestinal tuberculosis. Clinically hepatic tuberculosis is normal, without apparent clinical symptoms of liver diseases, and hence it is difficult to be diagnosed. Herein we report a case of pulmonary tuberculosis combined with hepatic

tuberculosis.

CASE REPORT A 40-year-old Chinese male who had no chronic obstructive pulmonary diseases, diabetes mellitus, hepatitis or hepatic cirrhosis in the past medical history or any congenital disease in his family manifested loss of appetite, fatigue for half a year and cough as well as night sweat for 2 months. The body temperature was normal. The

patient developed normally with moderate nutritional status, chronic disease face and physical weakness. Neither xanthochromia nor enlargement of the superficial lymph nodes was found all over the body skin The breath sounds of right lung were weak without moist rales being heard. In addition, wheezing sounds could not be heard in both two lungs. No rebound tenderness and muscle tension were found on the abdomen which was smooth and

soft. The liver could be touched 3 cm under the xiphoid process and 3 cm under the rib. The patient was sensitive to be percussed at the renal regions especially at the right side. The abdominal examination revealed negative shifting dullness in the abdomen and normal bowel sounds. Our initial diagnosis was lung cancer with liver metastases,

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The blood routine test showed normal white blood cells (WBCs), hemoglobins, and platelets. The TB antibody test was positive. The results of liver function test showed ALT 13 U/L, AST 24 U/L, and GGT126U/L. The antibody titers of Hepatitis A, Hepatitis B and Hepatitis C were normal. The antibody titers of tuberculosis were

negative. The lung cancer biomarker spectrum and alpha-fetoprotein (AFP) levels were normal. No acid-fast bacillus could be found in the sputum. The tuberculin test was negative. The chest CT showed multiple nodules combined with bronchial stenosis and lymphadenectasis in the mediastina at the right hilum of lung. The epigastrium CT showed lumps in the liver and retroperitoneal lymphadenectasis in the peritoneal cavity.. The abdominal color Doppler ultrasound revealed lumps in the liver (figure 1). The flexible bronchofiberscopy revealed stenosis at the lateral segment of

the right middle lobe, without any neoformation. The examination of bronchoalveolar lavage fluid revealed no acid-fast bacillus or tumor cells. The pathological examination of biopsy revealed granulomatous lesions in the bronchial mucosa of the right middle lobe suggesting the diagnosis of

tuberculosis (figure 2). The CT-guided

percutaneous lung puncture biopsy revealed granulomatous lesions, suggesting the possibility of tuberculosis(figure 3). Besides, the CT-guided percutaneous liver

puncture biopsy revealed chronic inflammatory changes in the strip-like fibrous tissues and plenty of caseification, suggesting more possibility of tuberculosis(figure 4). After the combined chemotherapy with INH, RFP, PZA, EMB (HRZE) for 10 days based on the confirmed diagnosis of pulmonary tuberculosis in the right middle lobar bronchus and hepatic tuberculosis, symptoms of the patient such as cough, expectoration night sweat and so on were relieved. The patient regained better appetite and better conditions, and then was discharged from hospital with discharge medication.

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DISCUSSION Hepatic tuberculosis is caused by Mycobacterium tuberculosis infection, invading the liver through hepatic artery, portal vein, umbilical vein, lymphatic system and direct extension. Though there is no generally accepted standard for the pathological classification of hepatic tuberculosis, it is usually divided into such types as nodules, abscess of liver, bile ducts and liver plasma membrane[1]. It may be difficult to be diagnosed clinically due to lack of specific clinical manifestations, and may be

unsuspected or confused with primary or metastatic carcinoma of the liver, especially when it coexists with other malignancies. The highly suspected cases

require

diagnostic confirmation based on the histological and bacteriological studies, as well as PCR analysis [2].

The main signs of hepatic tuberculosis include fever, poor appetite, fatigue, pain in the hepatic region or the epigastric region and hepatomegaly. It is often febrile in the afternoon with chills

and night sweat sometimes. Hepatomegaly is the main

symptom with more than half of patients having haphalgesia. Mild jaundice can be found in 15% patients due to the oppression of nodules against the hepatic ducts and bile ducts. Ascites can be found in 10% patients [1,3]. Diagnosis could be confirmed by liver biopsy through needle aspiration, diagnostic laparoscopy, exploratory laparotomy and finally autopsy.

The typical CT features of hepatic tuberculosis might be multiple lesions of varying density indicating that there are lesions in different pathologic stages coexisting in hepatic tuberculosis, including tuberculous granuloma, liquefaction necrosis, fibrosis or calcification [3]. Various types of hepatic tuberculosis have different imaging features, and typical CT and MR findings can be helpful for the diagnosis. However, these findings, though helpful for suggesting tuberculosis, can also be found in necrotic tumors such as metastatic carcinoma and hepatocellular carcinoma [4-5]. This article is protected by copyright. All rights reserved. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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According to the related domestic reports, hepatic tuberculosis is often misdiagnosed as liver cancer, liver abscess, benign tumor of liver, liver cysts, liver hydatid and so on, with the average rate of misdiagnosis of 93.1%. The CT-guided percutaneous transhepatic puncture biopsy of the liver has its satisfactory diagnostic value, which is generally recognized as one of the important ways for the diagnosis and differential diagnosis[5-6]. Compared with the percutaneous puncture biopsy of the lung guided by B-mode ultrasonography, CT has a high resolution and can clearly show the pathological changes of morphology, size, location and adjacent relationships of organs, tissues, and large blood vessels around it, with little influence on the imaging of the bones and gases, thus CT-guided percutaneous liver puncture biopsy can overcome the disadvantages such as inaccurate positioning, low success rate, and occurrence of complications when we need to take the focal biopsy hiding in the mediastinum and heart [7]. CT-guided percutaneous puncture biopsy of the liver is safe, efficient and minimally invasive. It can also play an irreplaceable role in the differential diagnosis and prognosis judgment of hepatic space occupying lesion. It can provide the pathological diagnosis of pathological changes, decrease the misdiagnosis rate, and guide the treatment regimens on the basis of the patients’ conditions. The CT-guided percutaneous puncture biopsy can also reduce the economic burden of the patients as well. It is also the internationally recognized gold standard. For the patients with hepatic space occupying lesions, we need to consider the whole body conditions of them in an all-inclusive manner. In addition to the consideration of solid lesions such as liver abscess and hepatic cancer, we need to exclude the possibility of hepatic tuberculosis. In this case reported, the clinical manifestations are characterized by the symptoms of digestive tract, with cough and night sweat. The tubercular antibody and tuberculin test are negative with no acid-fast bacillus in the sputum. The flexible

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bronchofiberscopy showed stenosis at the lateral segment of the right middle lobe, without neoformation, but pathological examination confirmed granulomatous lesions.

CT-guided percutaneous transhepatic biopsy of the lung and liver revealed granulomatous lesions and confirmed the diagnosis of pulmonary tuberculosis combined with hepatic tuberculosis. The clinical manifestations of hepatic tuberculosis which is easily confused by the signs of extrahepatic tuberculosis are non-specific and often misdiagnosed [8-9]. With the development of the technology of

CT-guided percutaneous transhepatic puncture biopsy, it will be of great importance in finding lesions timely to make diagnosis, giving effective treatment early to improve the cure rate of tuberculosis and reducing the germination of drug-resistant tuberculosis. In conclusion, hepatic tuberculosis is usually associated with atypical clinical manifestations. Imageological examination combined with imaging-guided fine needle aspiration biopsy may be the best method for the confirmed diagnosis. Anti-tuberculosis treatment is effective in most cases.

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References [1] Tang SJ,Gao W. Clinical TB learning [M]. Beijing: people's medical publishing

house 2011; 443-443.

[2] Huang WT, Wang CC, Chen WJ,

et al.The nodular form of hepatic tuberculosis:

a review with five additional new cases. J Clin Pathol. 2003 November; 56 (11): 835–839. [3]Vimalraj V, Jyotibasu D, Rajendran S, et al. Macronodular hepatic tuberculosis necessitating hepatic resection: a diagnostic conundrum. Can J Surg. 2007 Oct 10;50(5):E7-8. [4]Yu RS, Zhang SZ, Wu JJ, et al. Imaging diagnosis of 12 patients with hepatic tuberculosis. World J Gastroenterol. 2004 Jun 1;10(11):1639-42. [5] Zhang XZ, Lu Y. CT-guided transcutaneous fine-needle aspiration biopsy. Chin Med J. 1990.103:599-603

[6] Zhang XZ. Chest puncture biopsy by CT guidance. Chin J Tub Resp Dis, 2001,V24(4): 194-195 [7] Li C C,Liu S Y,Zhang DB. CT guided percutaneous lung biopsy .[J] Chin J Radiol.1998 V6(32):427-428 [8]Singh R, Kumar N, Sundriyal D, et al.Mixed pyogenic and tuberculous liver abscess: clinical suspicion is what matters. BMJ Case Rep.2013 Jun 28;2013. [9]Wu Z, Wang WL, Zhu Y, et al. Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. Int J Clin Exp Med. 2013,6(9):845-50.

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Figure legend Figure 1: Enhancement CT of thorax and epigastric region A

Enhancement CT of thorax displays: the right side of hilum of lung exists

multiple nodules combing with bronchial stenosis and mediastinum exists intensive shadow of multiple lymph nodes swelling. B The per cutem Puncture Biopsy on lung by CT-guided C

Enhancement CT of abdomen: liver exists multiple low-density shadows, which

are of uneven size with uneven and mild-to-moderate enrichment. D The per cutem Puncture Biopsy on liver by CT-guided

Figure 2: A,B:

the pathological tissues of bronchial mucous

Chronic

granulomatous

inflammation

comprehend

epithelioid

cells,

lymphocytes, Langerhans’ giant cells and caseous necrosis.

Figure 3

the tissues of lung by Puncture Biopsy

C,D: Caseous necrosis, surrounded by epithelioid cells, Lang-Han-Shi giant cells and lymphocytes. Figure 4 E,F:

the tissues of liver by Puncture Biopsy

Chronic granulomatous inflammation comprehend caseous necrosis epithelioid

cells and lymphocytes.

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Pulmonary tuberculosis combined with hepatic tuberculosis: a case report and literature review.

Tuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis, may invade all organs but mainly affect lungs. Most hepatic tuberculo...
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