Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.

Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase.

Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (≤ 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change.

High-intensity focused ultrasound in the treatment of experimental liver tumour.

This project aimed to determine the adequacy and accuracy of high-intensity focused ultrasound (HIFU) for ablating experimental liver tumour, and to assess imaging methods for monitoring the therapeutic results. The rabbit liver pseudotumour model was established by injection of Freund's complete adjuvant into the liver; the animals then received HIFU therapy via laparotomy at the focal point of the beam (1.1 MHz, 500 W/cm2, 20 s). The rabbits were sacrificed at scheduled times after treatment and liver tumours were examined histologically. Sequential imaging of the liver tumour was performed before and after HIFU treatment. HIFU accurately destroyed the rabbit liver tumour and induced coagulation necrosis 24 h later. Sonographic imaging studies revealed that characteristic changes occurred. A hyperechoic mass turned to a hypoechoic lesion with no Doppler signal, and a high echogenic rim appeared 24 h after HIFU treatment, correlating well with the pathological changes of a sonoablated lesion. These results verify that HIFU has the power to ablate liver tumour quite adequately and accurately, and that sonography is useful for monitoring sonoablated liver tumour.

Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer.

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P = 0.0008 and P = 0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P = 0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4 implanted subcutaneously, were randomly divided into four groups. Group I (n = 12) were the controls, group II (n = 12) were injected with iodized oil alone, group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P < 0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P < 0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.

Ultrastructural observation of liver tissue ablation induced by high-intensity focused ultrasound.

AIM: To observe the ultrastructural changes of liver tissues on normal rabbit ablated by high-intensity focused ultrasound (HIFU). METHODS: A single shot of 1.1 MHz focused ultrasound at an intensity of 500 W/cm(2) with 20-s duration of continuous exposure was applied intraoperatively in normal rabbit livers. Ultrastructural changes of the sonoablated lesion, as viewed by light and electron microscopy, were observed. RESULTS: Liver cells at the center of the sonoablated lesion showed irreversible degeneration immediately after HIFU treatment; electron microscopy showed that although the liver cells appeared normal histologically, irregularly shaped cavities of about 0.3-0.5 µm in diameter were present in the cytoplasm. CONCLUSION: Thermal damages may be the main mechanism of HIFU-induced ablation of liver tissues besides cavitation effect.

Elevated MHC class I and II antigens in cultured human embryonic myoblasts following stimulation with gamma-interferon.

The expression of major histocompatibility complex (MHC) antigens on the surface of cultured human embryonic myoblasts was studied by fluorescence microscopy. Class I or II MHC antigens were detected by monoclonal antibodies (MoAb) recognizing monomorphic determinants on HLA-A, B and C (class I), or HLA-DP, DQ and DR (class II) and a secondary fluorescein-labelled sheep anti-mouse immunoglobulin (Ig) antibody. Myoblasts were simultaneously identified using a MoAb directed against myosin light chains 1 and 2 (MLC1 and MLC2) and a combination of biotin-labelled sheep anti-mouse Ig antibody and Texas Red labelled streptavidin. We found that myoblasts demonstrated only very weak expression of either class of MHC but that, in the presence of more than 100 units of gamma-interferon (gamma-IFN) for 56-72 h, both class I and II MHC antigen expression increased significantly. During this time, class I antigen increased more than class II and at lower gamma-IFN concentrations. The implications of these findings for myoblast transfer therapy in Duchenne muscular dystrophy patients is discussed.

[Surgical treatment of old dislocation of radial head in children].

Isolated dislocation of radial head in 8 children, aged 2 to 12 years, was reported. Prominence of the dislocated radial head at the cubital fossa was the sign in common, either in fresh case (1) or in old one (7). The elbow function was normal except short of less than 30 degrees of flexion in 2 cases. The 1 fresh dislocation was treated by manual reduction and cast immobilization; while the old ones were reduced operatively without fascial reconstruction of annular ligament, followed by immobilizing cast which, if necessary, should be windowed over the area of radial head to apply pressure to keep the not-well seated radial head into place. Follow-up of 7 patients for a period of 2 to 15 years, averaging 5 years, showed normal anatomy and normal function in 6 patients and failure (redislocation) in 1. The operative technic and the post-operative management are described in the paper.