Chronic Active Hepatitis and Giant Multinucleated Hepatocytes in Adults Treated with Clometacin

Pessayre, Dominique; Degos, Françoise; Feldmann, Gérard; Degott, Claude; Bernuau, Jacques; Benhamou, Jean‐Pierre

doi:10.1159/000198597

Cited by 34 publications

(7 citation statements)

References 12 publications

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“…In addition to medications, such as clometacin, 50 diclofenac, 51 doxycycline, 11 , 17 amoxicillin/clavulanate, 12 dehydrocholic acid, 11 and testosterone analogue, 52 herbal remedies, 53 – 55 and dietary supplements 56 were also reported to have an association with PIGCH. The most commonly associated malignancy with PIGCH appeared to be chronic lymphocyte leukemia (CLL).…”

Section: Resultsmentioning

confidence: 99%

“…Instead, they had the appearance of active cells with abundant endoplasmic reticulum and numerous mitochondria, thus indicating that giant multinucleated hepatocytes were regenerative rather than degenerative cells, and the formation of giant multinucleated hepatocytes was due to nuclear division without cytoplasmic division. 50 However, in PIGCH associated with HCV, CLL, 37 and autoimmune hepatitis, 23 giant cells were strongly positive for keratin 8/18 (mature hepatocyte marker) and cyclin D1 (G1 phase marker), 37 and negative for Ki-67 (proliferation marker) and keratin 19/keratin 7 (intermediate hepatocyte makers), 23 hence indicating that nuclear division was a less likely explanation for the giant cell formation. On the other hand, the identification of intracellular plasma membrane remnants in the giant multinucleated hepatocytes indicated that the fusion of hepatocytes was a more likely mechanism for giant cell formation.…”

Section: Discussionmentioning

confidence: 99%

“…20 Some cases of PIGCH had features of autoimmune disorders (e.g., elevated autoantibodies) and improved after immunosuppressive therapy without having a specific autoimmune disease diagnosed. 11,36 Viruses associated with PIGCH included hepatitis C (HCV), 15,16,29,[37][38][39] human immunodeficiency virus (HIV), 16,28,39 human herpes virus-6 (HHV-6), 40 cytomegalovirus (CMV), 14,41,42 Epstein-Barr virus (EBV), 43,44 herpes simplex virus (HSV), 29 paramyxoviruses, 8,33,43,45 hepatitis A, 38,46,47 hepatitis B, 38 and hepatitis E. 48,49 In addition to medications, such as clometacin, 50 diclofenac, 51 doxycycline, 11,17 amoxicillin/clavulanate, 12 dehydrocholic acid, 11 and testosterone analogue, 52 herbal remedies, [53][54][55] and dietary supplements 56 were also reported to have an association with PIGCH. The most commonly associated malignancy with PIGCH appeared to be chronic lymphocyte leukemia (CLL).…”

Section: Distribution Of the Etiologymentioning

confidence: 99%

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Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis

Jiao¹,

Zhang²

2022

J Clin Transl Pathol

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Post-infantile giant cell hepatitis (PIGCH) is a rare disease entity in adults with a multifactorial etiology and widely variable clinical courses and outcomes. The factors associated with the worse outcomes of this disease entity are still unclear. We identified 68 PIGCH patients by searching PubMed and performed meta-analysis. Among the 68 patients, 32% of the cases were associated with autoimmune disorders, followed by 21% associated with viral infections, 10% with medication, and 7% with malignancy. Twenty-four percent of the patients had more than one etiological factor, and 6% had other uncommon etiologies or an etiology that could not be identified. At the time of this report, 17 patients had died of the disease (poor outcome), and 51 patients remained alive with the disease (good outcome). Compared to the patients with a good outcome, the patients with a poor outcome were characterized by older age, lower levels of platelets and albumin, higher level of total bilirubin, and a diffuse distribution pattern of giant cells in the liver. There were no differences in gender distribution, aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, etiological distribution, or other histological features, including interface hepatitis, necrosis, lobular inflammation, portal inflammation, cholestasis, or fibrosis. Further studies would be needed to better understand the disease mechanisms and unmask any additional etiological factors and targeted therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Distribution Of the Etiologymentioning

confidence: 99%

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Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis

Jiao¹,

Zhang²

2022

J Clin Transl Pathol

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“…Drug-induced autoimmune hepatitis (DIAH) has been reported for a number of agents (5), the most common of which are currently methyldopa (6-8), nitrofurantoin (9)(10)(11)(12)(13)(14), minocycline (15)(16)(17)(18)(19)(20)(21), and clometacin (22,23). Interferon is increasingly being cited as a possible cause (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Hepatitis and Thyroiditis Associated with Rifampin and Pyrazinamide Prophylaxis: An Unusual Reaction

et al. 2005

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KEY WORDS: autoimmune hepatitis; autoimmune thyroiditis; rifampin prophylaxis; pyrazinamide prophylaxis.Drug-induced autoimmune hepatitis (DIAH) and thyroiditis with rifampin and pyrazinamide has not been reported to our knowledge. We report on a 25-year-old male who presented with signs of acute anicteric hepatitis and subclinical thyroiditis 3 weeks after starting antituberculosis (anti-TB) prophylaxis. After discontinuation of the rifampin and pyrazinamide prophylaxis, his symptoms of hepatitis resolved, and liver enzymes and thyroid tests returned to normal after several months. Since neither rifampin nor pyrazinamide has been described so far as a triggering factor for autoimmune hepatitis and thyroiditis, the case is discussed and the literature reviewed. CASE REPORTA 25-year-old man in otherwise excellent health presented 3 weeks after the start of anti-TB prophylaxis. He was found to have a positive purified protein derivative (PPD) in May 2002 that was performed as part of a routine employment physical examination. A PPD 2 years earlier had been negative. He was unable to recall any exposure to TB, but he was a medical student at an urban medical center. A chest x-ray taken after the PPD was found to be unremarkable. The patient chose not to start anti-TB prophylaxis at this time, as he was asymptomatic. However, in October 2002, he was convinced to start a 2-month regimen of rifampin and pyrazinamide prophylaxis, which was the guideline at that time for treatment of latent TB (1). Three weeks after beginning prophylaxis, he presented with anorexia, fever, fatigue, and right upper quadrant pain. Physical examination was unremarkable except for mild right upper quadrant tenderness on deep palpation. No organomegaly or tenderness Manuscript . was noted. No skin eruption was present. The patient was a nonsmoker, but did consume alcohol, up to two six-packs of beer on the weekends. He had no other comorbid conditions. Aminotransferases at presentation were elevated, with an ALT of 749 IU/L (normal, 0-40 IU/L) and an AST of 938 IU/L (normal, 0-40 IU/L). Preprophylaxis baseline ALT and AST had been normal (12 and 22 IU/L, respectively). Serum total protein was 6.7 g/dL (normal, 6.0-8.5 g/dL), serum albumin was 3.8 g/dL (normal, 3.5-5.0 g/dL), and serum globulin was 2.9 g/dL (1.5-3.0 g/dL). Blood work also revealed an eosinophil count of 15%. Serological studies showed a positive antinuclear antibody (ANA) of >1:640 in a speckled pattern. Anti-smooth muscle antibody (ASMA) was elevated, at 1:80. Tests for acute and chronic viral infection, including hepatitis A, B, and C, mononucleosis, and cytomegalovirus, were all negative. Iron and copper studies were normal, and an abdominal ultrasound was unremarkable with normal echogenicity of the liver. One week after discontinuation of rifampin and pyrazinamide, the ALT was further elevated, to 1256 IU/L, and AST was 695 IU/L. INR was slightly prolonged, at 1.4 (normal, 0.9-1.1), but the bilirubin level was normal at 0.4 mg/dL (normal, 0.1-1.0 mg/dL). No liver biopsy w...

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“…In humans, the liver lesion characterized by formation of multinucleated hepatocytes is often found in neonates and infants and is called post-infantile giant cell hepatitis(PIGCH) [5], whereas it is very rare in adults. The cause of PIGCH has been considered to be viral infection [7,8], drug intoxication [6,8], or autoimmunity [1,3], but it is still obscure in some cases [4,8]. On the other hand, reports of giant cell hepatitis are strikingly few in animals [2].…”

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confidence: 99%

Giant Cell Hepatitis in Two Young Cats.

Suzuki

Nakayama

Doi

2001

The Journal of Veterinary Medical Science

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A very rare case of the liver lesion characterized by formation of multinucleated giant hepatocytes with inflammatory cell infiltration were observed in two young (1.5 years and 2 years old) cats bearing thymic malignant lymphoma. Histopathological features of this liver lesion were very similar to giant cell hepatitis (GCH) in human neonates and infants. Therefore, the lesion was diagnosed as feline GCH.

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Chronic Active Hepatitis and Giant Multinucleated Hepatocytes in Adults Treated with Clometacin

Cited by 34 publications

References 12 publications

Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis

Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis

Autoimmune Hepatitis and Thyroiditis Associated with Rifampin and Pyrazinamide Prophylaxis: An Unusual Reaction

Giant Cell Hepatitis in Two Young Cats.

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