C. Hoang

Cryoglobulinemia in chronic liver diseases: Role of hepatitis C virus and liver damage

BACKGROUND/AIMS Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study. METHODS The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. RESULTS The prevalence of mixed cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. CONCLUSIONS These findings suggest that HCV is a major cause of cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.

AIDS-related cholangiopathy. Critical analysis of a prospective series of 26 patients.

Several types of biliary tract abnormality of undertermined origin have been described among AIDS patients. The aims of this study are (1) to evaluate whether biliary tree involvement is in fact one or several homogeneous morphological entities, (2) to specify the role of CMV orCryptosporidium sp. infection, and (3) to evaluate the possible efficacy of treatment. Since ultrasound had revealed abnormality in the biliary tree, 26 consecutive AIDS patients underwent cholangiography. Cholangiograms enabled us to distinguish between two types of biliary tract involvement: (1) gradual and regular stenosis of the terminal portion of the common bile duct associated with dilation but without irregularity of the intrahepatic biliary ducts was present in 27% of our cases, and (2) distal stenosis of the extrahepatic biliary ducts combined with diffuse irregularity of the caliber of the intrahepatic bile ducts was present in 73% of our cases. Concomitant infection by CMV orCryptosporidium sp. was significantly more frequent when intrahepatic duct irregularities were present (94%) than when absent (14%,P<0.001). Anti-CMV treatment and sphincterotomy were unsuccessful in treating anomalies of the intrahepatic biliary tract. Conversely, sphincterotomy caused rapid and lasting disappearance of pain in all our patients. In conclusion, biliary tract involvement in AIDS patients is of two types. CMV infection and infection byCryptosporidium sp. are most frequent when the large intrahepatic ducts are implicated.

Inefficacy of intestinal secretory immune response to Cryptosporidium in acquired immunodeficiency syndrome

BACKGROUND/AIMS An alteration of the secretory immune response has been forwarded to explain frequent and chronic mucosal infections in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to explore the intestinal immunoglobulin (Ig) secretions in patients with AIDS and their relationships to cryptosporidiosis. METHODS Patients with AIDS and enteric cryptosporidiosis (n = 12), other enteric infections (n = 10), and no identifiable enteric pathogen (n = 10) and human immunodeficiency virus-seronegative controls (n = 18) were studied. The number of intestinal IgA and IgM plasma cells of the duodenal lamina propria mucosa and total and anti-Cryptosporidium IgA, IgM, and IgG were measured in serum and feces. RESULTS Although not significantly increased, the number of IgA and IgM plasma cells was greater in patients with AIDS (n = 20) than in controls (n = 5). In feces, total IgA outputs and specific anti-Cryptosporidium IgA levels were significantly higher in patients with AIDS and cryptosporidiosis than in the two other groups of patients with AIDS (P < 0.05 and P < 0.01, respectively) and controls (P < 0.001 and P < 0.01, respectively). Total fecal IgM output and specific anti-Cryptosporidium IgM coproantibodies were increased only in the Cryptosporidium-infected patients relative to the controls (P < 0.05). CONCLUSIONS Despite the development of pathogen-specific mucosal antibody responses, patients with AIDS and cryptosporidiosis fail to clear the parasite.

Long-term effects of interferon-α in five HIV-positive patients with chronic hepatitis B

Summary. Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long‐term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co‐infected with HIV and hepatitis B virus (HBV) (mean age 2 7 years) were given a 6‐month course of interferon (IFN)‐α2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340–553 mm‐3, their CDC stage was IIa‐III; all had histologically proven chronic hepatitis, with Knodells score ranging from 6–10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis δ virus (HδV) or hepatitis C virus (HCV) infection. Follow‐up was for 53 months on average (24–74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) sero‐conversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow‐up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well as in HIV‐negative patients.

Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective, double-blind, placebo-randomized study.

Background. Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. Methods. Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. Results. At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and &ggr;-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. Conclusions. A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.