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Infections and fever due to bacterial infections are well‐known complications of liver cirrhosis, and often trigger decompensation and death.1 Visceral leishmaniasis (VL), a protozoan infection endemic in the Mediterranean area, causes a febrile disease, the clinical and laboratory features (splenomegaly, pancytopenia, reduced serum albumin and increased γ‐globulin concentrations) of which largely overlap with those of cirrhosis.2,3 Although the areas where VL is endemic coincide with areas where the prevalence of cirrhosis is high, no study has described VL in patients with cirrhosis.
During a 12‐year period, all patients with cirrhosis admitted for decompensation and fever lasting more than 1 week, unresponsive to broad‐spectrum antibiotics, underwent diagnostic procedures for VL. For each case diagnosed as VL, three consecutive cases of bacterial infection observed in the same period were enrolled. Cirrhosis was defined by liver histology or clinical, laboratory, ultrasonographic and endoscopic findings. VL was diagnosed by the immunofluorescent‐specific antibody test (IFAT) and confirmed by the identification of Leishmania from Giemsa‐stained smears of bone marrow or spleen aspirates.4 Bacterial infections were diagnosed by standard clinical procedures. All patients were followed up for 6 months after diagnosis.
In total, 11 patients with VL and 33 with bacterial infections were enrolled. Table 11 summarises the main clinical and laboratory data at presentation.
Patients with VL received standard‐dose liposomal‐amphotericin B (l‐AmB; nine cases)5 or meglumine antimoniate (two cases). Fever resolved within 72 h in patients receiving l‐AmB and after 7 days in those receiving antimonials. No severe drug‐related adverse reaction was recorded. Improvement in haematological parameters and reduction in liver enzymes, spleen diameter and anti‐Leishmania antibody titre were recorded during the follow‐up period in all patients with VL. The Child–Pugh class rapidly and stably improved in patients with VL (fig 11).). The mortality was 17% for patients with bacterial infections and 0% for patients with VL.
VL was a troublesome diagnosis in patients with cirrhosis, as shown by the time from the onset of symptoms and diagnosis. This delay resulted from failure to consider this unusual diagnosis and was responsible for a progressive worsening in liver function. Indeed, once VL was cured, cirrhosis reverted to Child class A in all but one patient.
Apart from a long‐lasting fever, there were no clear‐cut clues to suspect VL. Some significant differences in the presentation data between VL and bacterial infections were found (table 11),), but their clinical use is hampered by a substantial overlap of the laboratory values between VL and bacterial infection cases. Only white blood cell and γ‐globulin data are of potential value.
IFAT serology is a sensitive and specific test for the diagnosis of VL in patients with cirrhosis; notably, IFAT was negative in all patients with bacterial infections and in 51 additional patients with cirrhosis without fever (table 11).). In a series including 16 patients with cirrhosis, a strip test using Leishmania K39 antigen was sensitive and specific.6 The diagnostic flow‐chart for patients with cirrhosis with unexplained fever should include the anti‐VL antibody test, thus avoiding the routine use of invasive diagnostic techniques. Once the diagnosis is established, l‐AmB is a safe and effective treatment.
The study was not designed to assess whether the patients with cirrhosis are at a higher risk of acquiring VL than those without cirrhosis. Assuming that there are 10000–20000 patients with cirrhosis per year in our area, the annual incidence of VL among patients with cirrhosis was 0.5–1/10000—that is, 8–17‐fold higher than the incidence (0.06/10000) among the adult population in the same area (p<0.001).7,8,9
Overall, the study underlines the need to consider this unusual cause of fever and decompensation in patients with cirrhosis when they are living in or have travelled through an area endemic with VL.
The study is part of a research project supported by Ministero Università e Ricerca Scientifica e Tecnologica (MURST), Rome, Italy.
Competing interests: None.