Liver histology in HIV/hepatitis C-coinfected and HCV-monoinfected patients with persistently normal alanine aminotransferases.

To the Editors: Information on liver histology of patients coinfected with HIV and hepatitis C virus who have persistently normal alanine aminotransferases (PNAL) is limited, and the data on the comparison of the liver histology between HIV/HCVcoinfected patients and HCV-monoinfected patients with PNAL come from a study involving only few cases. We describe a comparative investigation of 34 consecutive HIV/HCVcoinfected patients with PNAL (group HIV/HCV) and 30 HCV-monoinfected patients with PNAL (group HCV) who underwent liver biopsy (LB). The criteria used to define PNAL are those established in a previous study: normal alanine aminotransferase (ALT) serum levels in at least 3 consecutive determinations over a 1-year observation period before LB. Patients were enrolled at the time of the percutaneous LB from 1995 to 2005 at the Clinic of Infectious Diseases of San Raffaele University in Milan or at the Department of Infectious Diseases of the Second University of Naples. These 2 centers had been using the same laboratory and clinical approach for years and had cooperated in several investigations. Before LB, each patient signed an informed consent as established by the local ethics committee. For patients in group HIV/HCV, the epidemiological, clinical, and immunovirological data recorded at the baseline included risk factors for acquiring HIV and HCV infection, liver function tests, CD4 and CD8 cell counts, HCV genotype, HIV and HCV viral load, and routine tests. For patients in group HCV, the same data were recorded excluding those pertaining to HIV infection. The median duration of HCV infection in group HIV/HCV was 10.5 years (interquartile range: 5.8–14.04); it was impossible to calculate this parameter in group HCV because the time of infection was uncertain in most cases. Excluded from the study were patients treated with ainterferon (INF) or Peg-INF, alone or in combination with ribavirin (RBV), before LB was performed; those with an alcohol intake >40 g/daily for males and >30 g for females in the 6 months preceding LB; those circulating HBsAg or autoantibodies associated to autoimmune hepatitis; patients with genetic disorders inducing liver disease; and those who in the 6 months preceding enrollment had taken drugs known to potentially induce liver damage. Patients in group HIV/HCV were more frequently males (P < 0.02) and significantly younger than those in group HCV (P < 0.0001); more frequently they had HCV genotype 3 (38.2% vs 0%, P < 0.0001) or HCV genotype 4 (29.4% vs 0%, P < 0.0001); and more frequently stated a history of intravenous drug abuse (82.9% vs. 0%; P < 0.0001); conversely, HCV genotype 1 predominated in patients in group HCV (73.3% vs 32.2%, P < 0.0001) (Table 1). Patients in group HIV/HCV showed a good immunological status (CD4 = 564 6 314), but a nadir of CD4 #200 cells per microliter was recorded in 52.9% of cases. Of the 34 patients in group HIV/HCV, 27 (79.4%) were under effective highly active antiretroviral therapy at the time of LB, whereas 7 with a good immunovirological condition had been left untreated (Table 1). Patients in group HIV/HCV, compared with those in group HCV, showed a higher score of fibrosis (Ishak score) (2.16 1.5 vs 1.4 6 0.6, P < 0.05) and a higher prevalence of patients with fibrosis score 3–6 (23.5% vs 6.6%, P < 0.05) (see Figure, SupplementalDigital Content 1, http://links.lww.com/QAI/A34). A necroinflammation score <7 (Ishak score) was found in the majority of cases in both groups. Liver steatosis was graded as follows: score 1 = 1%–10% of hepatocytes with fatty deposition; score 2 = 11%–30%; score 3 = 31%–60%; score 4 $60%. The higher degrees of steatosis (scores 2–4) were more frequent in group HIV/HCV than in group HCV (32.4% vs 3.4%, P < 0.005). We also analyzed other histological liver lesions: lipogranulomas, portal eosinophils, portal neutrophils, portal plasma cells, parenchymal granulomas, hemosiderosis, mega mitochondria, Mallory bodies, germinal centers, multinucleated giant hepatocytes, hepatocytic dysplasia, sanded nuclei, ground-glass hepatocytes, glycogen nuclei, ballooning, sinusoidal lymphocytosis, acidophilic rhomboid-shaped hepatocytes, Kupffer cell hyperplasia, acidophil bodies, bile duct wall lesions, bile duct proliferation, pericellular fibrosis, perivenular fibrosis, and focal intralobular necrosis. These lesions were graded as absent, mild, moderate, or severe and named ‘‘overlapping liver lesions’’, according to Klatskin and Conn. A severe or more extensive expression of some overlapping liver lesions was more frequently observed in patients in group HIV/HCV than those in group HCV (Table 1): the differences were statistically significant for sinusoidal lymphocytosis (P = 0.031) and for acidophilic rhomboid-shaped hepatocytes (P = 0.0007) but not significant for acidophilic bodies, glycogen nuclei, ballooning, Kupffer cell hyperplasia, bile duct wall lesions, or bile duct proliferation (Table 1). The other overlapping liver lesions investigated were never or rarely observed. HCV viral load was not associated to adverse liver histology or to a particular HCV genotype or other parameters explored. The present study is, to our knowledge, the first performed on a substantial number of patients that compared the clinical presentation and liver histology of HIV/HCV-coinfected patients with PNAL with that of HCVmonoinfected patients with PNAL, and the only one investigating possible differences in the so-called ‘‘overlapping liver lesions’’ between these 2 groups. Of the previous studies, the study by Dr Gonzalez et al is the only Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions this article on the journal’s Web site (www.jaids.com).