Bartonella and the Liver

Research on HIV patients in the 1990s revealed the bacterium, Bartonella henselae, as the causative agent of cat scratch disease (CSD). These studies also reported patients who developed atypical CSD symptoms, including bacillary peliosis, suggesting that chronic Bartonella species infections (bartonellosis) may lead to impaired liver function in immunosuppressed individuals. Since then, case studies of patients show Bartonella species are increasingly implicated in hepatic (liver-related) irregularities. 

The liver is a large vital organ that plays a major role in keeping people healthy. When liver function is disrupted due to infection or other diseases, patients may develop a variety of symptoms, including acute symptoms that are non-specific, such as abdominal pain or weight loss, or more severe symptoms like jaundice or hepatomegaly (enlarged liver). This means there is a spectrum of differential diagnoses that may be suspected before hepatic bartonellosis is even considered. Physicians typically require a high clinical suspicion of Bartonella species infection before testing for it. Because of this, it is important for patients and physicians to be aware of bartonellosis risk factors when trying to determine the underlying cause of liver disease.

Hepatic (liver) bartonellosis in human beings is rare, with an estimated occurrence of 1-2% across all reported CSD cases. It is unclear what factors lead Bartonella species to initiate pathology of the liver, but the host’s immune status seems to play a large role. Researchers hypothesize that the host’s genetic makeup and age as well as the virulence of the bacterial strain could affect patient susceptibility. All of these variables make it difficult to determine the pathogenicity (disease-causing role) of Bartonella species in specific patient populations.

When the liver is involved in Bartonella species infections, the resulting lesions typically appear as granulomatous (inflammatory) lesions. Further research suggests that Bartonella species may induce vascular endothelial growth factor (VEGF) in host cells that may lead to vascular tumors in the liver.

The Bartonella species that have been reported in hepatic bartonellosis of humans thus far include B. henselae and subspecies of B. vinsonii. The sections below describe some cases of confirmed hepatic bartonellosis.

Bartonella henselae

A case report from 2007 describes an immunosuppressed woman who developed hepatic bartonellosis three years after undergoing liver transplant surgery. She presented with a fever of unknown origin, leading physicians to locate multiple lesions on her liver. Bartonella henselae infection was confirmed using histological techniques (looking at the tissue under a microscope) and PCR on initial tissue biopsies. After treatment with antibiotics, the woman’s fever and lesions resolved. The authors noted the importance of cat scratch disease being considered in cases of liver disease where patients are immunocompromised and have exposure to cats.

In contrast, a 2012 case report describes an immunocompetent woman with no prior liver disease and no direct contact with cats who developed granulomatous lesions on her liver. The patient experienced recurring abdominal pain, fever spikes, and worsening liver values over a two-year period. Physicians struggled to determine Bartonella as the causative agent despite repeated testing of blood, tissue, and serum samples for vector-borne pathogens. Eventually, Bartonella henselae was detected using the patented ePCR technology that is now available at Galaxy Diagnostics. After treatment with combination antimicrobial therapy, her symptoms resolved and her liver values normalized. This case report included Galaxy Diagnostics scientists among the authors.

In some cases, the granulomas that form on the liver appear as masses that require surgery to remove them. This occurred when a 10-year old presented with persistent fever for 12 days as well as a headache and abdominal pain. After treatment with antibiotics for 10 days, the physician was able to feel a mass on the liver. The surgeons removed part of the affected liver and found that Bartonella henselae was present via PCR of the tissue samples.

Bartonella vinsonii

The other species of Bartonella that has been implicated in multiple case reports of hepatic bartonellosis is Bartonella vinsonii. B. vinsonii is a complex species with distinct subspecies of varying genotypes being reported.

B. vinsonii berkhoffii, a species typically isolated from dog samples, was discovered in lesions from a 13-year-old boy’s liver in 2008. The boy had a history of several months of fatigue and feeling ill, but these symptoms were attributed to a positive mononucleosis test earlier in the year. When he presented with severe abdominal pain and an enlarged liver, a CT scan revealed tumors throughout his liver. A sample from the liver revealed the tumors were epithelioid hemangioendothelioma (EHE). Further diagnostic testing of blood and tissue samples using standard PCR as well as the patented ePCR technology that is now available at Galaxy Diagnostics found B. vinsonii berkhoffii genotype II. The physician treated with combination antimicrobial therapy for 12 weeks, resulting in inhibition of tumor growth and the patient’s remaining asymptomatic over the following year. This case report included Galaxy Diagnostics scientists among the authors.

A case study from 2015 describes how B. vinsonii arupensis contributed to inflammatory lesions found on the liver of an 11-year old girl presenting with high fever. The physicians had a high clinical suspicion of systemic cat scratch disease because the girl had recently gotten a kitten. Importantly, they decided to test samples from both the girl’s liver and the cat’s blood for Bartonella. The reference lab found B. vinsonii arupensis in both samples via PCR.

Conclusion

Overall, the risk of hepatic involvement in cases of bartonellosis is low, but the impact can be severe. More research is needed on specific factors that may increase the risk of hepatic involvement for a particular patient. Meanwhile, bartonellosis should be considered in unexplained liver disease, especially when there has been exposure to animals.

 

References

Álvarez-Fernández, A. et al. (2018). Bartonella infections in cats and dogs including zoonotic aspects. Parasites & Vectors, 11, 624. doi:10.1186/s13071-3152-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280416/#CR14

Breitschwerdt, E. B. (2017). Bartonellosis, One Health and all creatures great and small. Veterinary Dermatology, 28(1), 96-106 (e21). doi:10.1111/vde.12413 https://www.ncbi.nlm.nih.gov/pubmed/28133871/

Mazur-Melewska, K. et al. (2015). Cat-scratch disease: A wide spectrum of clinical pictures. Postepy Dermatologii i Allergologii, 32(3), 216-220. doi:10.5114/pdia.2014.44014 https://www.ncbi.nlm.nih.gov/pubmed/26161064/

Beerlage, C. et al. (2012). Bartonella vinsonii subsp. berkhoffii and Bartonella henselae as potential causes of proliferative vascular diseases in animals. Medical Microbiology and Immunology, 201(3), 319-326. doi:10.1007/s00430-012-0234-5 https://www.ncbi.nlm.nih.gov/pubmed/22450733/

Cheslock, M. A., & Embers, M. E. (2019). Human bartonellosis: An underappreciated public health problem? Tropical Medicine and Infectious Disease, 19(4), E69. doi:10.3390/tropicalmed4020069 https://www.ncbi.nlm.nih.gov/pubmed/31010191-

Breitschwerdt, E. B. et al. (2009). Isolation of Bartonella vinsonii subsp. berkhoffii genotype II from a boy with epithelioid hemangioendothelioma and a dog with hemangiopericytoma. Journal of Clinical Microbiology, 47(6), 1957-1960. doi:10.1128/JCM.00069-09 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691088/-

VanderHeyden, T. R. et al. (2012). Granulomatous hepatitis due to Bartonella henselae infection in an immunocompetent patient. BMC Infectious Diseases, 12, 17. Available at: https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-12-17

Iannaccone, R. et al. (2006). Peliosis hepatis: Spectrum of imaging findings. American Journal of Roentgenology, 187(1), W43-W52. doi:10.2214/AJR.05.0167 https://www.ajronline.org/doi/full/10.2214/AJR.05.0167

Thudi, K. R. et al. (2007). Cat scratch disease causing hepatic masses after liver transplant. Liver International, 27(1), 145-148. doi:10.1111/j.1478-3231.2006.01386.x https://www.ncbi.nlm.nih.gov/pubmed/17241393?dopt=Abstract

Murano, I. et al. (2001). Giant hepatic granuloma caused by Bartonella henselae. The Pediatric Infectious Disease Journal, 20(3), 319-320.  https://journals.lww.com/pidj/Fulltext/2001/03000/GIANT_HEPATIC_GRANULOMA_CAUSED_BY_BARTONELLA.23.aspx

Melzi, M. L. et al. (2015). Hepatic granulomatous lesions caused by systemic Bartonella vinsonii subsp. arupensis infection in a child. The Pediatric Infectious Disease Journal, 34(12), 1416-1417. doi:10.1097/INF.0000000000000904 https://journals.lww.com/pidj/fulltext/2015/12000/Hepatic_Granulomatous_Lesions_Caused_by_Systemic.36.aspx

Kempf, V. A. J. et al. (2001). Evidence of a leading role for VEGF in Bartonella henselae-induced endothelial cell proliferations. Cellular Microbiology, 3(9). https://doi.org/10.1046/j.1462-5822.2001.00144.x https://onlinelibrary.wiley.com/doi/full/10.1046/j.1462-5822.2001.00144.x

Dehio, C. (2003). Recent progress in understanding Bartonella-induced vascular proliferation. Current Opinion in Microbiology, 6(1), 61-65. https://www.ncbi.nlm.nih.gov/pubmed/12615221