Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B

YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.published_or_final_versio

A one-year trial of lamivudine for chronic hepatitis B

Background and Methods: In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. Results: Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events. Conclusions: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.published_or_final_versio

T lymphocyte activation in chronic hepatitis B infection: Interleukin 2 release and its receptor expression

The present study was undertaken to examine early T lymphocyte activation in chronic hepatitis B virus (HBV) carriers. Nineteen hepatitis B surface antigen-positive patients (eight with liver cirrhosis and 11 with chronic hepatitis) and 18 healthy controls were studied in a period free of other infection. Mitogen-stimulated cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production were studied in peripheral blood mononuclear cells cultured for 24 h. No difference was demonstrated between the patients and healthy controls in the cellular interleukin 2 receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production. Pokeweed mitogen-stimulated interleukin 2 production in lymphocytes from cirrhotic patients was significantly lower than that of the noncirrhotic patients. However, the cellular and soluble interleukin 2 receptor levels did not differ between the two groups of chronic HBV carriers. Despite the fact that is has been suggested that autoreactive T cells have a role in mediating the development of chronic liver diseases associated with HBV infection, this study fails to demonstrate a defective T lymphocyte activation in these patients. The observed reduction of interleukin 2 production from activated lymphocytes may be related to the severity of liver impairment, rather than the HBV infection itself.link_to_subscribed_fulltex

Effects of α-interferon and prednisone on serum-soluble interleukin-2 receptor (sIL-2R) in chronic hepatitis B infection

The level of serum-soluble interleukin-2 receptor (sIL-2R) was measured in 32 patients to investigate the effect of prednisone and α-interferon therapy on chronic hepatitis B virus infection. All the patients were seropositive for hepatitis B surface antigen and hepatitis B e antigen, with histological evidence of chronic persistent or chronic active hepatitis. Twenty-six patients received oral prednisone, followed by subcutaneous recombinant α- interferon, and six patients received multivitamin tablets and served as controls. After 4 wk of prednisone in reducing dosage, serum sIL-2R fell significantly from 673.6 ± 52.9 U/ml to 584.8 ± 39.4 U/ml (mean ± SE, p < 0.05). It rose to 733.4 ± 45.7 U/ml (p < 0.05) on the 4th wk of interferon, but returned to pretreatment level at completion of interferon. There was a significant correlation between serum sIL-2R and alanine aminotransferase levels (r = 0.36, p < 0.001). The level of serum sIL-2R before treatment and its response to prednisone and interferon were not useful in predicting seroconversion of hepatitis B e antigen and anti-hepatitis B e.link_to_subscribed_fulltex

Lamivudine for chronic hepatitis B [2] (multiple letters)

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The effect of a combined visual efficiency and perceptual-motor training programme on the handwriting performance of children with handwriting difficulties : a pilot study

Title on author’s file: The effect of a combined visual efficiency and perceptual perceptual-motor training programme on the handwriting performance of children with handwriting difficulties202205 bcfcAccepted ManuscriptOthersPolyU Central Research GrantPublishe

Anti-Neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in chinese

Inflammatory bowel diseases are uncommon in the Chinese, but the incidence is rising. Their differentiation from infective colitis is often not clear-cut and diagnosing inflammatory bowel diseases can be difficult in Asia. We have studied Chinese patients with ulcerative colitis (N = 19) and Crohn's disease (N = 12) for anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA). Patients with enteric fever (N = 29) and irritable bowel syndrome (N = 24) were recruited as controls. Seventy-three percent of ulcerative colitis patients exhibited either p-ANCA (31%) or c-ANCA (42%) by IIF. Twenty-five percent of Crohn's disease patients were found to be p-ANCA positive. However these ANCA were nonreactive to anti-α granule, antiproteinase 3, antimyeloperoxidase, or antilactoferrin. All positive patients had extensive colitis. Sera collected from patients suffering from enteric fever and irritable bowel syndrome were negative for ANCA by IIF and ELISA. We concluded that the detection of ANCA is helpful in diagnosing inflammatory bowel diseases. Further attempts to characterize these autoantibodies are needed.link_to_subscribed_fulltex