Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

Canh, Hiep Nguyen; Harada, Kenichi; Ouchi, Hirofumi; Sato, Yasunori; Tsuneyama, Koichi; Kage, Masayoshi; Nakano, Masayuki; Yoshizawa, Kaname; Takahashi, Atsushi; Abe, Masanori; Kang, Jong Hon; Koike, Kazuhiko; Inui, Ayano; Fujisawa, Tomoo; Takaki, Akinobu; Arinaga‐Hino, Teruko; Torimura, Takuji; Suzuki, Yoshiyuki; Fujiwara, Keiichi; Zeniya, Mikio; Ohira, Hiromasa; Tanaka, Atsushi; Takikawa, Hajime

doi:10.1136/jclinpath-2016-204271

Cited by 67 publications

(59 citation statements)

References 74 publications

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“…In our model of TCE‐induced AIH, immune cells infiltrate the liver leading to a cascade of inflammatory events that are counter‐balanced by an increase in interleukin (IL)‐6‐related signaling molecules that are important in liver regeneration and repair (Gilbert et al, ). Similar findings have been reported idiopathic AIH in humans (Nguyen Canh et al, ). The bi‐directional interaction between the gut and liver has been documented.…”

Section: Introductionsupporting

confidence: 90%

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

Khare

Gokulan

Williams

et al. 2018

J of Applied Toxicology

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The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)-induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500 μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154 days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue-associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high-dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high-dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin-33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin-3, granulocyte-macrophage colony-stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.

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Section: Introductionsupporting

confidence: 90%

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

Khare

Gokulan

Williams

et al. 2018

J of Applied Toxicology

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“…The severity of each pathological finding varies among individual cases. Among these features, prominent lobular and perivenular necroinflammatory activity, pigmented macrophages, cobblestone appearance of hepatocytes, plasma cell infiltration, and emperipolesis are useful for the pathological diagnosis of AIH with acute presentation . Moreover, plasma cell infiltration could be a diagnostic requirement for AIH with acute presentation as previous reports and our present survey have revealed plasma cell infiltration in over 80% of biopsy samples …”

Section: Autoimmune Hepatitis With Acute Presentationsupporting

confidence: 67%

“…37,38 Alternatively, the histogenesis of CN in AIH with acute presentation is not related to the autoimmune process. 44 According to our survey of Japanese patients, 45 the histological features of AIH with acute presentation include several that overlap with those of classical AIH: (i) lobular (parenchymal) changes including CN (collapse and lytic type), centrilobular congestion/hemorrhage, centrilobular endothelial cell injury/central vein endothelitis, cobblestone appearance of hepatocytes, pigmented macrophages, and centrilobular fibrosis; and (ii) portal/periportal changes, including portal inflammation, interface hepatitis, portal plasma cell infiltration, hepatic rosette formation in periportal areas, bile duct injury, and portal/periportal fibrosis. The severity of each pathological finding varies among individual cases.…”

Section: Histology Of Aih With Acute Presentationmentioning

confidence: 99%

Challenges and difficulties in pathological diagnosis of autoimmune hepatitis

Harada

Canh

Ohira

2017

Hepatology Research

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Autoimmune hepatitis (AIH) with acute presentation is widely recognized as a distinct clinical entity, and its clinicopathology has been extensively studied. In most cases, AIH with acute presentation is merely acute exacerbation of classical chronic AIH, but pure acute-onset AIH without previous symptoms of chronic liver disease is also encountered. Rapid diagnosis and initiation of immunosuppressive treatment are necessary for both acute exacerbation and acute-onset to prevent fatal liver failure. The diagnostic criteria commonly used for classical AIH are generally applicable to acute exacerbation, but acute-onset AIH may present with additional pathological features. These features include an acute hepatitis phase characterized by centrilobular necrosis. However, centrilobular necrosis is also a feature of drug-induced liver injury, and there are no known histological characteristics exclusive to acute-onset AIH. Moreover, the possibilities of drug-induced AIH and immune-mediated drug-induced liver injury make diagnosis even more difficult. At present, liver biopsy is mandatory for the diagnosis of AIH with acute presentation, but careful consideration of all clinicopathological signs is necessary for differential diagnosis.

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“…35 In another recent retrospective histological evaluation of 87 Japanese patients with acute AIH, it was shown that, in accordance with the US-ALFSG findings, 3 the patients had prominent lobular and perivenular necroinflammation (including centrilobular necrosis), pigmented macrophages, and cobblestone appearance of hepatocytes along with typical AIH features, like plasma cell infiltration and emperipolesis. 38 All 34 AS-AIH patients were promptly treated within 7-10 days after the onset of symptoms. Of note, the patients had a median INR of 1.52, which shows that they were not "too sick" and that treatment was initiated promptly enough in order to interrupt the catastrophic process and prevent deterioration of liver function and ALF development.…”

Section: Figurementioning

confidence: 99%

Prompt initiation of high‐dose i.v. corticosteroids seems to prevent progression to liver failure in patients with original acute severe autoimmune hepatitis

Zachou

Arvaniti

Lygoura

et al. 2018

Hepatology Research

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Aims: The definition of original acute severe autoimmune hepatitis (AS-AIH) is unclear. However, its rapid recognition and early treatment is potentially life-saving. Therefore, we present herein an open, real-world observational study for the assessment of the efficacy and safety of early high-dose i.v. corticosteroids in original AS-AIH patients.Methods: Prospectively collected data from 184 AIH patients were analyzed retrospectively. Original AS-AIH defined as an acute symptomatic presentation of newly diagnosed AIH (transaminases >10× upper limit of normal, bilirubin >4 mg/dL, and international normalized ratio [INR] ≥1.5) without histological lesions of chronic disease.Results: Thirty-four of 184 (18.5%) patients had original AS-AIH.These patients were promptly treated with i.v. corticosteroids (either 1 g methylprednisolone for 3 consecutive days followed by i.v. 1 mg/kg/day prednisolone or i.v. 1.5 mg/kg/day prednisolone from the beginning). Only 1/34 (2.9%) died due to sepsis; none required liver transplantation during follow-up (65 [1-175] months). No significant differences were detected in baseline characteristics between original AS-AIH patients and those with insidious presentation (not-AS-AIH; n = 117) apart from antinuclear antibodies negativity (P = 0.038), and higher immunoglobulin G, transaminases, INR, and bilirubin in original AS-AIH patients (P = 0.001 for all). Complete response and corticosteroids withdrawal (for patients treated >12 months) were significantly more frequent in original AS-AIH (n = 28) than in not-AS-AIH (n = 79; P = 0.026 and P = 0.016, respectively). Presence of original AS-AIH was the only independent predictor for achieving complete response.Conclusions: Prompt initiation of high-dose i.v. corticosteroids in original AS-AIH seems safe and efficient as it prevents disease deterioration and the need for liver transplantation. The long-term overall survival of these patients was high (97% for 5.3 years), and the long-term treatment response and corticosteroids withdrawal rates were higher compared to not-AS-AIH patients.

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Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

Cited by 67 publications

References 74 publications

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

Challenges and difficulties in pathological diagnosis of autoimmune hepatitis

Prompt initiation of high‐dose i.v. corticosteroids seems to prevent progression to liver failure in patients with original acute severe autoimmune hepatitis

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