Taglietti et al. Journal of Medical Case Reports 2010, 4:332 http://www.jmedicalcasereports.com/content/4/1/332 cells, many of them forming discrete clumps in zone three. They contained yellow-brown ceroid pigment, staining with PAS after diastase digestion. The portal tracts were expanded and slightly oedematous, and con- tained a moderate inflammatory cell infiltrate composed of lymphocytes and neutrophils, with many eosinophils and histiocytes. Focal interface hepatitis was present in some portal tracts. The interlobular bile ducts were pre- served, and ductular reaction was evident at the edge of portal tracts. Zone one hepatocytes were swollen, and staining was pale. Glycogenated nuclei were present in periportal hepatocytes (Figure 2). Finally, granules of stainable iron were seen in sinusoidal lining cells and in periportal hepatocytes, associated with a more diffuse staining indicative of ferritin deposits. Fatty changes and Mallory-Denk bodies were not seen. Mild pericellular fibrosis was present in perivenular areas. By day 22, our patient’s transaminase and bilirubin values were decreased and his clinical condition improved. The glycemic index and insulin index were normal. On day 30, the patient was discharged in good clinical condition. His final blood results were: ALT 76 U/L, AST 58 U/L, alkaline phosphatase 298 U/L, total bilirubin 6.0 mg/dL, direct bilirubin 4.1 mg/dL, GGT 98 U/L and C-reactive protein 0.10 mg/dL. At follow-up examination on day 90, our patient was asymptomatic and his liver blood tests gave normal results. The pat- tern of blood test results is shown in Table 1. Discussion Cholestatic hepatitis has previously been reported in one patient during HCTZ treatment [9]. In that paper, the diagnosis of HCTZ-induced cholestatic liver injury was based on the laboratory tests and the Naranjo probabil- ity scale, indicating a possible relationship between the Figure 2 Mild portal tract edema with a light mixed inflammatory cell infiltrate and periportal hyperglycogenated nuclei (hematoxylin and eosin). Page 3 of 4 drug and liver injury. However, to date no histopatholo- gical description of the associated liver changes has been reported, to the best of our knowledge, and our case represents the first documentation of clinical and histopathological liver damage in the course of HCTZ treatment. In our patient we excluded an obstruction of the bili- ary tract (for example, hepatic and pancreatic neo- plasm, biliary calculosis), primitive biliary cirrhosis, sclerosing cholangitis, autoimmune disorders of the liver and infective causes for the increased transami- nase values, including viral hepatitis. Based on our patient’s history and on his score on the Naranjo prob- ability scale, which indicated a probable relationship between HCTZ and development of liver injury [10], we suspected that his hepatic damage was probably related to the HCTZ therapy. To confirm our hypoth- esis, we examined a liver biopsy, which showed acute hepatocellular-cholestatic injury associated with altera- tions of glucose metabolism in the liver, which was consistent with our clinical hypothesis of liver toxicity by HCTZ. Because a recent article [11] had demonstrated how visceral fat redistribution, liver fat accumulation, low- grade inflammation, and aggravated insulin resistance are all adverse effects caused by HCTZ therapy, we plotted a glycemic index and an insulin index for our patient, which gave normal results. A possible explana- tion for this was the concomitant treatment with olme- sartan, which may prevent hyperglycemia [12]. In addition, the HCTZ treatment duration was relatively short (40 days), possibly too short to cause marked alteration of glucose metabolism, and our patient had no known risk factors for developing diabetes. Conclusion In conclusion, in the differential diagnosis of cholestatic hepatitis, clinicians should be aware of the possibility of liver damage in the course of HCTZ therapy. Consent Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Author details 1II Division of Infectious Diseases, Istituto Nazionale per le Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico ‘Lazzaro Spallanzani’, Rome, Italy. 2Department of Pathology, Istituto Nazionale per le Malattie Infettiv, Istituto di Ricovero e Cura a Carattere Scientifico ‘Lazzaro Spallanzani’, Rome, Italy. 3Laboratory of Electron Microscopy, Istituto Nazionale per le Malattie Infettive, Istituto di Ricovero e Cura a Carattere Scientifico ‘Lazzaro Spallanzani’, Rome, Italy. 4Radiology Department, San Camillo-Forlanini Hospital, Rome, Italy.