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Acute hepatitis A virus (AHAV) infection is a self-limited condition that usually spontaneously recovers in 2–8 weeks. While in children under 6 years of age AHAV is often asymptomatic, >70% of adults manifest symptoms together with typical laboratory findings [1]. AHAV is serologically diagnosed by the detection of anti-HAV IgM, which persists 2–6 months after infection. Laboratory results during AHAV show a marked increase (usually 10 to 40 times the upper reference limit [URL]) in serum alanine aminotransferase (ALT) activity, together with high total bilirubin (TB) (average peak of 171.0 μmol/L, mainly consisting of the conjugated form) and moderately (<3 URL) increased alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) [2]. With resolution of AHAV, conjugated bilirubin (CB) is rapidly cleared and its serum concentrations return to normal quickly. However, 10%–20% of patients develop prolonged cholestasis lasting for >6 months [1]. Bilirubin, which is a major end-product of heme breakdown, is physiologically glucuronidated in the liver and then excreted into the bile. The mechanisms of bilirubin excretion, and of hyperbilirubinemia causes, are largely understood. Unconjugated bilirubin (UB) enters the hepatocyte by passive transmembrane diffusion combined with active mediated transport. In the hepatocyte, UB is bound to ligandin and transported to the endoplasmic reticulum, where it is conjugated into bilirubin glucuronide by UDP glucuronosyltransferase (UGT) 1A1, and excreted into the bile by ATP-binding cassette (ABC) transporters ABCC2 and, to a lesser extent, by ABCG2. Under pathophysiological conditions, such as acute hepatitis or cholestasis, the CB back into blood by the basolateral ABCC3 transporter and then the solute carrier organic anion (SLCO) transporters 1B1 and 1B3 mediate its hepatic reuptake [3]. Several inherited disorders characterized by impaired bilirubin conjugation or transport result in various degrees of unconjugated or conjugated hyperbilirubinemia, respectively [4]. Here, we report a case of prolonged severe hyperbilirubinemia in a patient with pre-existing AHAV, in which we were however, unable to show an evident persistence of cholestasis. A 33-year-old man was admitted at the Emergency Department of our hospital on April 7, 2017, 6 weeks after an AHAV diagnosis performed in another hospital. The patient, strongly jaundiced, presented asthenia, nausea, diarrhea, pruritus and hyperchromic urine. Blood tests revealed a moderate increase of serum ALT activity (202 U/L; URL: 59 U/L), in line with the expected AHAV resolution, but an unexpectedly markedly elevated serum TB (625.9 μmol/L, with CB of 480.5 μmol/L; TB URL: 20.5 μmol/L, CB URL: 5.1 μmol/L). The presence of antiHAV IgM (slightly positive) and anti-HAV IgG confirmed the previous AHAV diagnosis. Other concomitant conditions (such as hepatitis B and C infection, syphilis, autoimmune disease and drug toxicity) were excluded. Steroid therapy was immediately started, but without any clinical improvement or significant decrease in serum TB/CB concentrations (Figure 1). A magnetic resonance cholangiopancreatography (MRCP) was therefore carried out, revealing no signs of intraor extra-hepatic cholestasis, besides those already suggested by the steadily normal values of GGT and the only slight (≤2 times the URL) *Corresponding author: Felicia Stefania Falvella, UOC Patologia Clinica, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, 20157, Milan, Italy, E-mail: stefania.falvella@asst-fbf-sacco.it Elena Angeli and Laura Cordier: UOC Malattie Infettive I, ASST Fatebenefratelli-Sacco, Milan, Italy Emilio Clementi: Dipartimento di Scienze Biomediche e Cliniche ‘Luigi Sacco’, Università degli Studi, Milan, Italy Mauro Panteghini: UOC Patologia Clinica, ASST FatebenefratelliSacco, Milan, Italy; and Dipartimento di Scienze Biomediche e Cliniche ‘Luigi Sacco’, Università degli Studi, Milan, Italy

An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?