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Mycobacterium chimaera Hepatitis

A New Disease Entity

Shafizadeh, Nafis, MD*; Hale, Gillian, MD, MPH; Bhatnagar, Julu, PhD; Alshak, Najeeb S., MD*; Nomura, Jim, MD

The American Journal of Surgical Pathology: February 2019 - Volume 43 - Issue 2 - p 244–250
doi: 10.1097/PAS.0000000000001179
Original Articles
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Mycobacterium chimaera was identified as a species within the Mycobacterium avium complex in 2004. Until recently, it was predominantly seen in immunocompromised patients. In 2015, an outbreak of disseminated M. chimaera disease was described in European patients after undergoing open-heart surgery in which contaminated heater-cooler water units were used. Using whole genomic sequencing and phylogenetic analysis, investigators found a highly clonal outbreak from the German manufacturing site of the heater-cooler water units. This outbreak has now proven to be world-wide. Patients present with fever, fatigue, and weight loss months to many years after surgery. They are found to have systemic manifestations, including endocarditis, pancytopenia, renal dysfunction, chorioretinitis, and hepatitis. Preliminary reports suggest a high mortality rate despite aggressive treatment. In some patients, the predominant laboratory abnormalities are elevations in liver function tests, leading to diagnostic hepatobiliary work-ups, including liver biopsy. The pathologic changes in the liver have not yet been described. Herein, we report the clinicopathologic findings of the largest series of M. chimaera liver disease in the United States to date: 7 cases within a large, multihospital health care network. Five (71%) patients died of disease, despite aggressive treatment. Liver function test abnormalities were predominantly biliary: mean values of alkaline phosphate 288 U/L, aspartate aminotransferase 79 U/L, alanine aminotransferase 64 U/L. All 7 biopsies showed a consistent and characteristic dual pattern of injury: small, ill-formed collections of sinusoidal histiocytes with rare multinucleated giant cells, and scattered architectural changes of venous outflow obstruction. Two (29%) cases showed mild pericellular fibrosis. Nodular regenerative hyperplasia was seen in 2 (29%) cases, consistent with a sinusoidal/venous obstructive pattern of injury. We postulate that the sinusoidal location of the granulomas contributes to the venous obstructive changes. Recognition of this characteristic dual pattern of injury can allow pathologists to suggest the diagnosis and prompt the appropriate diagnostic and therapeutic interventions.

*Department of Pathology

Division of Infectious Diseases, Kaiser Permanente Southern California, Los Angeles, CA

Division of High-Consequence Pathogens and Pathology, Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, GA

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Nafis Shafizadeh, MD, Department of Pathology, Kaiser Permanente Southern California, Woodland Hills Medical Center, Woodland Hills, CA, 91365 (e-mail: nafis.x.shafizadeh@kp.org).

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