A close relationship between viral hepatitis B and Toll-like receptor 2 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship of Toll-like receptor 2 (TLR2) and viral hepatitis B through testing the expression of TLR2 in liver tissues of patients infected with HBV and in HepG2 and HepG2.2.15 cell lines.</p><p><b>METHODS</b>Expression of TLR2 was determined by Elivision immunohistochemistry in liver tissues from patients with chronic viral hepatitis B (CHB), chronic severe hepatitis (CSH), from healthy controls and from cells of HepG2 and HepG2.2.15 hepatocellular carcinoma cell lines. Direct immunofluorescence flow cytometry was used to detect TLR2+ cell percentage and mean fluorescence intensity (MFI).</p><p><b>RESULTS</b>The intensity of TLR2 expression in liver tissues of CHB and CSH was significantly higher than that of the healthy controls (probability value less than 0.01). The positive staining was mainly located in the cytoplasm and on some cell membranes. In CHB, the intensity of TLR2 expression was positively correlated with the grade of necroinflammatory activity (r=0.597, P less than 0.01). There were significant differences of serum total bilirubin levels with different grades of positive staining of TLR2 (P less than 0.05). In liver tissues of the CHB patients, the positive staining of TLR2 was shown in small foci. MFI of TLR2 (10.7+/-2.8) and TLR2+ cell percentage (16.3%+/-7.0%) of HepG2.2.15 cells were both significantly higher than those of HepG2 cells (1.0+/-0.3, 0.4%+/-0.1%, P less than 0.01).</p><p><b>CONCLUSIONS</b>Expression of TLR2 is closely correlated with hepatitis B, especially to the grades of its necroinflammatory activity.</p>

Clinical characteristics of and the related factors to the relapse of chronic hepatitis B after lamivudine withdrawal / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the cases of chronic hepatitis B relapse after lamivudine withdrawal, and to find clinical characteristics and related factors to them.</p><p><b>METHODS</b>46 cases of chronic hepatitis B relapse after lamivudine withdrawal were investigated and followed up. The diagnosis and the course of the diseases before therapy with lamivudine, the dosage, effects, period of treatment, the reasons for lamivudine withdrawal, the biochemistry, immunological and virulogical data in each period, YMDD mutation, pre-C mutation and prognosis after relapse were recorded.</p><p><b>RESULTS</b>The periods of treatment of 32.6% of patients in this group were shorter than 52 weeks. The HBV DNA of 93.6% of patients turned negative at the time of lamivudine withdrawal and returned to positive in all of those patients when relapsed; of the 6.4% of patients who did not turn negative at the time of lamivudine withdrawal, their HBV DNA was elevated more than 2 log when relapsed. A majority of patients (71.7%) did not ask their physicians when they decided to withdraw from lamivudine. There were 61.5% of the other patients who withdrew from lamivudine on the advice of physicians but they were not followed up. The state of their illness in 71.7% (33/46) patients was more severe than before their lamivudine therapy. In these cases, the YMDD mutation was detected in 78.8% of patients (chi2 = 23.23, P<0.01), and pre-C mutation was detected in 84.8% of patients (chi2 = 21.04, P<0.01), higher than that in the cases with aggrevation of their illnesses before the lamivudine therapy. The median time between lamivudine withdrawal and relapse was 12 weeks; it was negatively correlated with ALT (r = 0.32, P<0.05) detected at the time of lamivudine withdrawal. The severity of the illness at the time of relapse was related with age (r = 0.40, P<0.01) and YMDD mutation (r = 0.31, P<0.05). The prognosis was related with the age of the patient (r = 0.49, P<0.01), the diagnosis (r = 0.39, P<0.01), TBil (r = 0.46, P<0.05) and ALT (r = 0.32, P<0.05) detected before lamivudine therapy, HBeAg became negative when lamivudine was withdrawn (r = 0.31, P<0.05), TBil (r = 0.55, P<0.01) and PTA (r = 0.57, P<0.01) detected when relapsed.</p><p><b>CONCLUSION</b>A majority of patients did not follow the lamivudine treatment recommendation of the experts group on lamivudine clinical practice in China. The major reason for relapse perhaps was revived HBV DNA multiplication, which induces damage of hepatocytes after lamivudine withdrawal. The YMDD mutation and/or pre-C mutation may be one of the factors that aggravate the damage of hepatocytes during the relapse. The factors including age of the patient, diagnosis before the treatment, TBil and ALT detected before lamivudine therapy, HBeAg turning to negative when lamivudine is withdrawn, and TBil and PTA detected during relapse may all impact the prognosis.</p>