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 Table of Contents  
Year : 2021  |  Volume : 10  |  Issue : 3  |  Page : 320-323

Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice

1 Department of GI Surgery, School of Digestive and Liver Diseases, IPGME and R, Kolkata, West Bengal, India
2 Department of Gastroenterology, School of Digestive and Liver Diseases, IPGME and R, Kolkata, West Bengal, India
3 Department of GI Pathology, School of Digestive and Liver Diseases, IPGME and R, Kolkata, West Bengal, India
4 Department of GI Radiology, School of Digestive and Liver Diseases, IPGME and R, Kolkata, West Bengal, India

Date of Submission28-Apr-2021
Date of Acceptance26-May-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Arkadeep Dhali
Department of GI Surgery, School of Digestive and Liver Diseases, IPGME and R, Kolkata, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmy.ijmy_92_21

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Granulomatous hepatitis is an uncommon presentation of tuberculosis (TB). It is even more peculiar to have TB confined to the liver alone with no pulmonary or a disseminated form. In either form, there is the usual presentation of nonprogressive cholestatic jaundice, but no documented case with fluctuating jaundice in the literature was found. In order to highlight this rare presentation aiding the right diagnosis, we present one such case of a 46-year-old woman with no known comorbidities, who complained of fluctuating and painless type of jaundice, associated with fatiguability, pruritus, and weight loss. Preliminary blood investigations showed anemia and cholestatic pattern of jaundice. Ultrasonography and computed tomography imaging showed hepatomegaly with heterogeneous texture. Magnetic resonance cholangiopancreatography further revealed features of cholecystitis with hepatic ducts near proximal common bile duct showing postinflammatory change. The periampullary region was normal. Sputum acid-fast staining and cartridge-based nucleic acid amplification test were negative. Eventually, liver biopsy was done which showed caseating granulomas with Langhans giant cells. The tissue was abundant in acid-fast bacilli. The patient was started on a 9-month course of first-line Antitubercular treatment (ATT) and responded well. Fluctuating jaundice is a rare and undocumented presentation of primary hepatic TB and can cause diagnostic dilemmas.

Keywords: Antitubercular treatment, fluctuating jaundice, primary hepatic tuberculosis

How to cite this article:
Dhali A, Dhali GK, Ghosh R, Sarkar A. Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice. Int J Mycobacteriol 2021;10:320-3

How to cite this URL:
Dhali A, Dhali GK, Ghosh R, Sarkar A. Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice. Int J Mycobacteriol [serial online] 2021 [cited 2022 Dec 2];10:320-3. Available from: https://www.ijmyco.org/text.asp?2021/10/3/320/325508

  Introduction Top

Granulomatous hepatitis refers to the presence of granulomas in the liver, caused by multiple etiologies including primary biliary cholangitis, tuberculosis (TB), drug induced, Crohn's disease, collagen vascular diseases, lymphoreticular malignancies, sarcoidosis, paraneoplastic, and primary immune deficiency disorders. The most common cause among these worldwide is TB.[1],[2],[3] TB is a disease of global importance, with the Indian subcontinent estimated to bear 20% of the global burden.[4] Even though TB is predominantly known to involve the lungs, it can affect several other organ systems. Involvement of liver as a part of disseminated TB is seen in up to 50%–80%, but localized hepatobiliary TB is very uncommon.[5] Even though the occurrence of localized hepatic TB is uncommon, a comparative study by Chien et al. suggests that miliary and local forms of TB have similar clinical presentation and pathological features.[6] Granulomatous hepatitis usually presents with cholestatic jaundice. However, there is no documented case of granulomatous hepatitis presenting as fluctuating jaundice – a feature of periampullary carcinoma. We describe a unique case of primary granulomatous hepatitis with fluctuating jaundice.

  Case Report Top

A 46-year-old woman with no known comorbidities came with the complaints of recurrent on and off yellowish discoloration of the skin and sclera for 2 years. The jaundice was painless and fluctuating (periods of anicteric phase in between icteric phase), associated with itching – a cholestatic feature. The patient also complained of fatigue and undocumented but significant weight loss. On examination, the patient was malnourished, with mild pallor. There was hepatomegaly, a firm and nontender liver with sharp margins and regular surface palpable 4 cm below the right costal margin in the midclavicular line. There were no other palpable masses, and examination of other systems was unremarkable. There were no signs of liver cell failure. At the end of clinical examination, the main differential diagnoses considered were periampullary carcinoma, common bile duct (CBD) calculi, HIV cholangiopathy, autoimmune hepatitis, chronic viral hepatitis (hepatitis B and C), hemobilia with hepatocellular carcinoma, and ascariasis of the liver.

Preliminary blood investigations [Table 1] showed mild anemia, elevated levels of liver enzymes, and conjugated hyperbilirubinemia, with normal coagulation profile. Viral hepatitis markers were negative. HIV ELISA was negative. An ultrasonography of the abdomen was done as the initial imaging and it showed hepatomegaly with coarse echotexture, with partially contracted and thick-walled gallbladder. There was no evidence of any obstructive biliopathy or periampullary pathology. A multidetector computed tomography (CT) was performed which showed hepatomegaly with heterogeneous texture, with a few prominent vessels in the left lobe, possibly collaterals [Figure 1]. To completely rule out a periampullary pathology, a magnetic resonance cholangiopancreatography (MRCP) was performed which confirmed the hepatomegaly with heterogeneous signal changes and features suggestive of cholecystitis (gallbladder wall thickening). MRCP also revealed narrowing of proximal CBD with void signals – favoring possible collateral formation narrowing the CBD. A triple-phase CT with thin slicing (slice thickness 1.5 mm) showed similar findings, with no evidence of features suggestive of hepatic malignancy.
Figure 1: Computed tomography image showing hepatomegaly with heterogeneous texture

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Table 1: Serial biochemical parameters suggestive of fluctuating jaundice

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Upper gastrointestinal (GI) endoscopy had no contributory findings. With periampullary pathology being unlikely and the evidence from imaging, inflammatory conditions such as autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and infiltrative pathologies of the liver such as sarcoidosis and TB were considered. The patient was tested for autoimmune markers (anti-liver/kidney microsomal antibodies, anti-mitochondrial antibodies, antinuclear antibodies, anti-smooth muscle antibodies, serum immunoglobulin G) which were negative. Chest X-ray [Figure 2] was normal. Serum angiotensin-converting enzyme levels were within normal limits ruling out sarcoidosis. Sputum was tested for TB by microscopy for acid-fast bacilli (AFB) and cartridge-based nucleic acid amplification test (CBNAAT) which were both negative. With the etiology still inconclusive, a percutaneous liver biopsy was taken and sent for histopathological examination, showing large confluent caseating granulomas in both lobules and portal triad with Langhans giant cells suggestive of TB [Figure 3]. Other causes of granulomatous hepatitis such as collagen vascular diseases, drug-induced hepatitis, lymphoreticular malignancies, primary immune deficiencies, and toxin ingestion were highly unlikely in this case as preliminary examination and investigations were not suggestive of any of those. The tissue was tested for AFB, and it was abundant in it. CBNAAT performed with the tissue sample also detected tubercular bacilli with no rifampicin resistance. Line probe assay was done to rule out any other resistance to first-line drugs, as in India, isolated isoniazid resistance is documented in many cases. With the diagnosis of TB, and no pulmonary, abdominal, or central nervous system involvement, this was considered a primary TB of the liver.
Figure 2: Chest X-ray within normal limits

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Figure 3: H and E image of liver biopsy showing caseating granuloma with Langhans giant cell

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The patient was started on the antitubercular treatment (ATT) consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol regimen for the intensive phase of 2 months and HRE regimen for the continuous phase for 7 months. The treatment given was the full dose as per the regimen, even though the liver enzymes were elevated. Ursodeoxycholic acid was given for controlling pruritus. Clinically symptoms such as easy fatiguability and yellowish discoloration of eyes improved.

Serial monitoring of the biochemical and hematological parameters was done during the course of treatment to look for prognosis, and a decreasing trend in the levels of deranged biochemical parameters was seen. Hence, the treatment with ATT was established to be beneficial. A close eye was kept on serum aspartate transaminase and alanine transaminase levels for possibility of ATT-induced transaminitis/hepatitis. A repeat CT imaging of the abdomen was done after 1 year, which was found to be normal, and hence, repeat liver biopsy was not performed to establish microbiological eradication of the disease. The patient recovered with no other complications.

  Discussion Top

This case is a unique presentation of a rare condition. With primary tubercular granulomatous hepatitis itself being uncommon and there being a few documented cases in the current medical literature, all rare presentations must be kept in mind to aid the diagnosis as it is a treatable disease but without prompt intervention can cause mortality. With the initial presentation of painless fluctuating jaundice, anemia, and weight loss, there was a high suspicion of adenocarcinoma of the ampulla of Vater. However, with no evidence of any periampullary pathology in imaging and endoscopy, a liver pathology had to be considered. Due to the CT pointing toward an infiltrative liver pathology, a triple-phase CT was done which pointed more toward an inflammatory etiology. Due to the endemicity of TB in India, sputum was tested for AFB and CBNAAT which being negative excluded a primary pulmonary TB. Radiological imaging, upper GI endoscopy, and colonoscopy showed no evidence of a primary abdominal TB or tubercular peritonitis. The diagnosis of granulomatous hepatitis was only made after histopathological evidence, pointing the etiology toward TB. Keeping this in mind, it was warranted to search for unusual presentations of this condition. Hence, a PubMed search was conducted with the keywords “primary granulomatous hepatitis,” “tuberculosis,” and “fluctuating jaundice.” The more common presentations of tubercular granulomatous hepatitis were easy fatiguability, fever of unknown origin, and hepatomegaly and less commonly progressive obstructive jaundice.[7] Other presentations documented were that of acute liver failure[6] and masquerading as intrahepatic cholangiocarcinoma.[8] To the best of our knowledge, localized granulomatous hepatitis presenting with fluctuating jaundice has not been documented before.

Comparing existing medical literature, we have found that isolated granulomatous hepatitis due to TB does not cause hyperbilirubinemia to the extent of 12 mg/dl which was found in our case because of which we came to the conclusion that it was not only granulomatous hepatitis but also tubercular cholangiopathy which created the unusual clinical picture. Furthermore, in the absence of immunodeficiency, abundance of AFB on tissue sample of granulomatous hepatitis is very rare. In the presence of immunodeficiency, a much-disseminated form was expected.[9]

Nontuberculous mycobacteria, although a rare causative organism for similar presentation, mostly presents skin and soft-tissue infection or disseminated infection.[10] These infections are seen mostly in immunocompromised state or patients with underlying malignancy, which was not the case for us. On biopsy, they can show they show fibrin-ring granuloma whereas Mycobacterium tuberculosis shows caseating granuloma.[11] Often, these hepatic granulomas mimic metastasis on radiological imaging, and misdiagnosis or delayed diagnosis can result in serious morbidity.[12],[13]

Hepatobiliary TB is a treatable disease. Even though liver enzymes are elevated, treatment with antitubercular drugs is warranted. A close eye has to be kept on the transaminases to pick up ATT-induced hepatotoxicity.[14],[15] Hasanain et al. have proposed the use of cholecalciferol in prophylaxis of ATT-induced liver injury.[16] The earlier the treatment is initiated, the better the outcome. If undiagnosed, it may warrant a liver transplant or even lead to mortality. Hence, it is very important that the right diagnosis is made early in the disease progression. In order to do this, it is imperative that all kinds of presentations and diagnostic dilemmas of this uncommon condition be made available in the literature to aid the clinician.

Learning points

  • TB, being an endemic disease of the Indian subcontinent, should be considered while enlisting the differential diagnoses
  • Fluctuating jaundice is a rare and undocumented presentation of primary hepatic TB and can cause diagnostic dilemmas
  • Abundance of AFB in the absence of immunodeficiency is a very unique occurrence
  • Full dose of ATT is recommended in the treatment of primary tubercular granulomatous hepatitis even in the setting of elevated enzymes, with close follow-up.

Ethical consideration

This case report is presented in accordance with the Declaration of Helsinki and with informed consent of the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Doppalapudi H, Markus JT, Parekh U. Granulomatous Hepatitis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 5, 2021.  Back to cited text no. 1
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Prabhudesai R, Lawande D, Gondal G, Keny S. Primary hepatic tuberculosis masquerading as intrahepatic cholangiocarcinoma. Indian J Tuberc 2019;66:310-3.  Back to cited text no. 3
Santra G. Etiological spectrum of recurrent jaundice in adults: A retrospective observational study from a tertiary care center. International Journal of Medicine and Public Health. 2016;6(1):35-39.  Back to cited text no. 4
Culver EL, Watkins J, Westbrook RH. Granulomas of the liver. Clin Liver Dis (Hoboken) 2016;7:92-6.  Back to cited text no. 5
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Chien RN, Lin PY, Liaw YF. Hepatic tuberculosis: Comparison of miliary and local form. Infection 1995;23:5-8.  Back to cited text no. 7
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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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