Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects

Patients who were diagnosed with ALA at the National Taiwan University Hospital (a 2500-bed university hospital and largest referral center for HIV/AIDS in Taiwan) were enrolled from March 1, 1990 to February 28, 2006 in this retrospective study. Detailed medical records, including demographic data, disease status, clinical presentation, risk factors of HIV infection, laboratory findings, treatment, and outcome were reviewed. CD4 count, plasma viral load, and concomitant opportunistic infection(s) records were analyzed if HIV infection was diagnosed. The study described herein was approved by the Institutional Review Board and was in accordance with the Declaration of Helsinki.

Study patients were considered to have ALA if image studies had demonstrated the presence of intra-hepatic abscesses and were accompanied with histological, serological, or clinical evidence of amebic infection [4‐6]. Three typical conditions were classified as ALA. First, patients with histological evidence of erythrophagocytic trophozoites identified in aspirates or biopsy tissue were diagnosed with ALA. Second, patients with a titer over 1:128 in the indirect haemagglutination (IHA) serologic assay were also included in the group of ALA cases. Third, patients without underlying biliary tract disease who responded well to metronidazole monotherapy, but had positive image studies were also considered as ALA cases, even if their serum IHA titer was less than 1:128 (because the IHA titer assay only has an intermediate sensitivity). Patients who responded well to metronidazole monotherapy were defined as those individuals in which fever or other clinical symptoms/signs improved after 3 days of metronidazole monotherapy. In addition, patients who had specimen such as blood or aspiration fluid with fungus or bacteria pathogens that were concomitantly isolated, were excluded from this study to avoid the enrolment of patients with mixed infection. If ALA recurred during the study period, data for the first time diagnosis was collected.

Patients were considered to have concomitant amebic colitis if trophozoites were found in stools or biopsy specimens from colon fibroscopic examination.

During the study period, 37 patients met the diagnostic criteria for ALA. HIV serum test results were obtained in 33 patients. Five (15.2%) patients had negative HIV test results and 28 (84.8%) patients were HIV-positive. Between 1990 and 1994, there was only one case of ALA every year; most patients had an unknown HIV infection status. In 1995, three cases of ALA were recorded, two of which had HIV-coinfection. Since then, the number of ALA cases increased gradually. In 1999, six patients had ALA, with five (82.4%) being coinfected with HIV. After 2002, the rate of ALA patients coinfected with HIV increased to 100% (9/9) (Figure 1). This significant increase prompted us to determine the characteristics of ALA patients with and without HIV infection.

The demographic characteristics of patients with and without HIV infection are listed in Table 1. The mean age was 44.2 ± 10.3 years in HIV-negative patients and 36 ± 10.1 years in HIV-infected patients. No female patients were included in either of the above mentioned groups. The five HIV-negative patients had a history of traveling to or living in endemic areas, including Thailand (n = 1), Burma (n = 2), Pakistan (n = 1), and the Philippines (n = 1). Of the 28 HIV-infected patients, four (14%) had traveled to Thailand within one month of the ALA episode, and 24 (86%) had a history of homosexual behavior. Remarkably, more than half (15/28, 54%) of the HIV-infected ALA patients were found to have HIV infection after they were diagnosed with ALA. Ten (36%) patients developed ALA after HIV had been diagnosed (2 months to 10 years later). The remaining three (10%) patients were found to be HIV-infected 4 months to 3 years after the diagnosis of ALA. Among these three patients, one was diagnosed with HIV infection during the second recurrence of ALA while the other two were diagnosed with HIV infection during other opportunistic infection episodes.

Of the 28 HIV-infected patients, nine (32%) were hepatitis B virus (HBV) carriers and four (14%) were hepatitis C virus (HCV) carriers. One patient was co-infected with HBV and HDV (hepatitis D virus), and another patient was co-infected with HBV and HCV. Serum Venereal Disease Research Laboratory (VDRL) examination was also positive in 12 (43%) of the HIV-infected patients.

Fever (>38°C) was the most common clinical symptom in ALA patients (100% in the HIV-negative group and 64% in the HIV-infected group, P = 0.29). Other symptoms included abdominal pain (40% in the HIV-negative group and 57% in the HIV-infected group, P = 0.64) and diarrhea (20% in the HIV-negative group and 36% in the HIV-infected group, P = 0.64). Four patients initially presented with right-flank pain and were treated inappropriately for urinary tract infection. The correct diagnosis was obtained later after treatment failed and after image studies were obtained. Some non-specific complaints included cough (n = 6), abdominal fullness (n = 3), anorexia (n = 3), body weight loss (n = 3), and general malaise (n = 3).

Seven patients had amebic colitis diagnosed at the same time (two in the HIV-negative group; five in the HIV-infected group). Five patients were diagnosed with histological findings of amebic trophozoites (four patients via colonoscopy biopsy, one via laparotomy biopsy). Another two patients had trophozoites in their stool specimens. Three patients also had peritonitis complication (one in the HIV-negative group; two in the HIV-positive group). One case of peritonitis was caused by liver abscess rupture and the other case was caused by colitis rupture. None of these patients had empyema, pericarditis, or brain abscess complications.

All five HIV-negative ALA patients had IHA titers over 1:128 (from 1:512 to 1:16,384). Of the 28 HIV-infected patients, 24 had IHA titers over 1:128 at the onset of ALA. Four HIV-infected patients had IHA titers remaining below 1:64 during the entire treatment course, but had typically good responses to metronidazole monotherapy.

In the HIV-infected group, the mean CD4 count (data of 24 patients) was 266.95/μL (14 to 798/μL) at the time of ALA diagnosis. Five patients had CD4 counts higher or equal to 350/μL (20%). Nine patients had CD4 counts between 200 and 349/μL (38%). Ten patients (42%) had CD4 counts below 200/μL. Plasma viral loads (data of 18 patients) ranged from undetectable levels (< 400 copies/mL) to > 750,000 RNA copies/mL. Further comparison between patients with IHA titers > 1:128 and patients with IHA titers < 1:64 revealed no significant different in the distribution of CD4 (P = 0.39) (Table 2). Five patients developed an opportunistic infection at the same time. One patient had a hairy leukoplakia and his CD4 count was 223/μL. The other four patients had oral candidiasis and their CD4 counts were 14/μL, 84/μL, 229/μL, and 367/μL, respectively.

All patients had a good response to metronidazole monotherapy; the mean treatment duration was 14.9 days (range: 7–33 days; 17 ± 3.7 days in HIV-negative patients and 14.4 ± 5.6 days in HIV-infected patients). Eradication therapy with idoquinol was also used in one (20%) HIV-negative patient and 22 (79%) HIV-infected patients (one of whom did not receive idoquinol during the first infection but only when the infection recurred).

The condition of the patients during hospitalization was benign, and all patients were alive at the time of discharge. Follow-up was generally uneventful. ALA recurred in only three patients (one HIV-negative patient and two HIV-positive patients). Of the two HIV-infected patients who had recurrence of ALA, one never received eradication therapy with idoquinol in the first episode. In addition, one patient had recurrent amebic colitis, but no liver abscess despite receiving eradication therapy with idoquinol during the first infection episode.