Incidence and characteristics of benign liver space-occupying mass in 17 721 patients with chronic hepatitis B: a color Doppler ultrasound-based case-control study / 南方医科大学学报

OBJECTIVE@#To analyze the incidence and risk factors of benign liver space-occupying mass in patients with chronic hepatitis B (CHB) and the ultrasound features that differentiate these masses from small hepatocellular carcinoma.@*METHODS@#We retrospectively analyzed the color Doppler and clinical data of 17 721 patients with CHB treated in the Hepatology Unit of Nanfang Hospital between January, 2016 and December, 2017. The data were compared with those of 21629 healthy control subjects undergoing routine physical examination in the Center of Heath Management of Nanfang Hospital during the same period.@*RESULTS@#Compared with the control subjects, the patients with CHB had significantly higher incidences of hepatic cysts (11.8% 8.7%, 0.05). Sonographically, the benign liver masses commonly showed homogeneous echo within the lesion with clear boundaries and regular shape. Hepatic hemangioma was distinctively hyperechoic in 83.32% (1579/1895) of the patients, while small hepatocellular carcinoma presented with weaker peripheral and internal blood flow signals with a lower flow velocity in the arteries and a higher flow velocity in the portal vein. Liver cirrhosis nodules mostly showed a mixture of strong and weak echoes (79.60%; 7637/9595) without blood flow signal within or around the nodule; an increased volume of the nodule accompanied by heterogeneous echoes within the nodule indicated an increased probability of malignant lesion. Hepatic cysts often displayed no echo within the lesion, but the echo could be enhanced posteriorly.@*CONCLUSIONS@#The patients with CHB are at a significantly higher risk of developing hepatic cysts, hepatic hemangiomas and hepatic cirrhosis nodules than the control population, and an older age and the male gender are associated with a higher incidence of hepatic cysts or cirrhosis. The differences in the sonographic and hemodynamic features can help to differentiate hepatic benign mass from malignant lesions, and kinetic changes in sonography can be used to monitor potential malignant transformation of the cirrhotic lesions.

The MRI characteristics of intraspinal extramedullary epidural lesions / 实用放射学杂志

Objective To explore the imaging characteristics and make the differential diagnosis of intraspinal extramedullary epidural lesions. Methods 23 cases with intraspinal extramedullary epidural lesions confirmed by puncture or surgical pathology were selected for retrospective analysis of the lesion morphology,MRI signs and the relationship between the lesion and surrounding tissues.Results Intraspinal extramedullary epidural lesions were more often located at thoracic spinal canal.The shapes of lesions were always various.The malignant tumors were irregular.It could damage the adjacent bone and grew surrounding the spinal cord.Leaping growth and multiple vertebral involvements could be seen in metastasis.The complex components of lesions were related to heterogeneous signal intensity on MRI,which could be presented with hypoGto hyperGintense on T1 WI and T2 WI.The angiolipoma showed hypoGto hyperGintense on T1 WI,and the hyperGintense signal could be suppressed with fatGsuppressed sequence.Meningioma tended to present with homogeneous signal on both T1 WI and T2 WI, with dural tail on contrast MRI.All of the lesions were moderately or significantly enhanced on contrast MRI.Conclusion Intraspinal extramedullary epidural lesions include a wide range of lesions,and the components of lesions are very complex.Among them,the distinctive MRI characteristics include the lesions containing fat and vascular components,besides malignant lesions invading adjacent tissues.Comprehensive analysis of the shape and signal of lesions,as well as the relationship between lesions,and surrounding structures is very helpful in differential diagnosis of intraspinal extramedullary epidural lesions.

Analysis of clinical characteristics of 22 906 gravidas with Hepatitis B Virus infection / 实用医学杂志

Objective To analyze the clinical characteristics of gravidas with HBV in Nanfang Hospital from 2008 to 2014. Methods 22 906 gravidas were retrospectively investigated. Results The HBsAg positive rates were 11.64% and 6.16% when the gravidas were divided into Cantonese and non-Cantonese groups (χ2 =193.370, P < 0.005). The ALT abnormal rates in HBeAg positive and HBeAg negative gravidas were 17.96% and 6.68% (χ2=62.594, P<0.005). Conclusion The HBsAg positive rate of gravidas in Guangdong and the ALT abnormal rate of HBeAg positive gravidas are higher.

Association between viral load and gestational diabetes mellitus in women with chronic hepatitis B / 实用医学杂志

Objective To analyze the GDM of 336 cases with chronic HBV in pregnancy. Methods According to HBV DNA≥1.0 × 103 IU/mL, participants were divided into HBV DNA (+) or (-) group. 409 cases without HBV were selected as control group. Differences on GMD incidence between groups and virus load and OGTT blood sugar correlation were compared. Results The incidence of GDM of HBV DNA (+) or (-) group was 16.77% and 17.71%, which is higher than that in HBV group (10.27%). The difference is significant (P < 0.05). The correlation index between HBV DNA and fasting blood-glucose is r = 0.005, P = 0.610, the result of which is not statistically significant. But correlation index between HBV DNA and blood sugar at 1 h , 2 h are r = 0.082, 0.086; P = 0.000, 0.000, the result of which is statistically significant. Conclusion The oc-currence of GDM were higher in HBV DNA (+) or (-) group. The viral load is positively related with blood sugar of glucose tolerance at 1 h or 2 h.

Treatment options in HBeAg-positive chronic hepatitis B patients with a poor response to 24-week interferon monotherapy / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of 4 treatment options for HBeAg-positive chronic hepatitis B (CHB) patients following a suboptimal response to 24-week interferon monotherapy.</p><p><b>METHODS</b>The data of 193 HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy were collected from Nanfang Hospital between September, 2010 and January, 2013. According to the subsequent treatments, the patients were divided into group A with additional entecavir or adefovir, group B with further interferon monotherapy, group C with conversion to NAs therapy, and group D with direct therapy withdrawal, and the biochemical and virological results at weeks 24, 48 and 72 were analyzed in the 4 groups.</p><p><b>RESULTS</b>At week 48, the HBV DNA negative rates and serum alanine aminotransferase (ALT) normalization rates were both significantly higher in group A and C than in group B (P<0.05); in group A, ETV therapy subgroup had a significantly higher HBV DNA negative rate than ADV therapy subgroup at week 48 (90.3% vs 59.5%, Χ=8.255, P=0.004). At week 72, 39.7%(27/68) of the patients in group A achieved HBeAg seroconversion, a rate significantly higher than those in groups B (Χ=4.238, P=0.040) and C (Χ=7.681, P=0.006); the HBV DNA negative rate and ALT normalization rate in group A were 85.3%(58/68) and 86.8%(59/68), respectively, both significantly higher than those in group B (Χ=23.018, P<0.001; Χ=5.987, P=0.014) but comparable to those in group C (P>0.05). In the two subgroups in group A, the HBV DNA negative rate and HBeAg seroconversion rate were both significantly higher in ETV subgroup (Χ=9.823, P=0.002; Χ=5.450, P=0.020). In group D, all the patients remained HBeAg-positive with abnormal ALT levels and high level of HBV DNA.</p><p><b>CONCLUSION</b>For HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy, combined treatment with NAs (especially ETV) and extension of the treatment course can significantly improve the HBeAg seroconversion rates, HBV DNA negative rates, and ALT normalization rates.</p>

Clinical analysis of chronic hepatitis B with concurrent hepatitis e antigen and antibody during antiviral therapy / 实用医学杂志

Objective To evaluate the clinical significance of chronic hepatitis B (CHB) with concurrent hepatitis e antigen (HBeAg) and antibody (anti-HBe) during antiviral therapy. Methods A total of 115 CHB patients with concurrent HBeAg and anti-Hbe detection during antiviral therapy were enrolled in this retrospective study. All patients received pegylated-IFN-alpha-2a (Peg-IFNα-2a, n = 50) or entecavir (ETV, n = 65) for antiviral treatment. Their biochemical virological and serological response and clinical outcome were detected and analyzed. Results Among the patients treated with Peg-IFNα-2a, 31 (62.0%) achieved HBeAg seroconversion and 6 (12.0%) achieved HBsAg seroconversion at the end of treatment. About 35.4% of patients, who received ETV, achieved HBeAg seroconversion and none of them achieved HBsAg seroconversion at the end of treatment (P < 0.05). Conclusion High rates of HBeAg seroconversion and HBsAg loss could be achieved in CHB patients, with co-existence of HBeAg and anti-HBe, who received Peg-IFNα-2a, but not ETV therapy.

Construction of full-length human bladder cancer-specific antibody libraries based on mammalian display technology / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct full-length human bladder cancer-specific antibody libraries for efficient display of full-length antibodies on the surface of mammalian cells.</p><p><b>METHODS</b>The total RNA was isolated from peripheral blood mononuclear cells from patients with bladder cancer. The repertoires of IgG1 heavy chain variable region (VH) and Kappa light chain were amplified by RT-PCR using specific primers. The antibody genes were inserted into the vector pDGB-HC-TM to construct the bladder-cancer-specific antibody libraries of heavy chains and light chains. Ten clones from each library were randomly picked for gene sequencing and transient transfection into FCHO cells to analyze antibody display on mammalian cell surface by flow cytometry after staining with corresponding fluorescent labeled antibodies.</p><p><b>RESULTS</b>The libraries of bladder-cancer-specific antibody heavy chain (IgG1) and light chain (LCk) were successfully constructed. Seven out of the 10 clones randomly selected from the heavy chain library and 9 out of the 10 clones from the light chain library showed correct open reading frame, coding for 7 unique VH and 9 unique LCk. The combinatory library size reached 3.32×10(11).</p><p><b>CONCLUSION</b>We have successfully constructed a full-length human bladder-cancer-specific antibody library with a combinatory diversity of 3.32×10(11) based on mammalian display technology, which can be used for screening monoclonal antibodies against bladder-cancer-associated antigens.</p>

Analysis of the factors for predicting the outcomes of interferon-α and entecavir treatments for chronic hepatitis B with positive HBeAg / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the predictive factors of the therapeutic effects of interferons (IFNs) and entecavir (ETV) treatments for 48 weeks in patients with chronic hepatitis B (CHB) positive for HBeAg.</p><p><b>METHODS</b>This retrospective analysis compared the treatment efficacy of IFNs and ETV in 129 CHB patients positive for HBeAg. Twenty-seven of the patients were treated with PEG-IFNα-2a (180 µg once a week, PEG-IFN group), 51 patients with conventional IFNα (5 MIU three times a week, IFN group), and 51 with ETV (0.5 mg once daily, ETV group) for 48 weeks.</p><p><b>RESULTS</b>After completion of the treatment cycles, the patients in ETV group showed a significantly higher HBV DNA undetectable rate and a significantly lower HBeAg seroconversion rate than those in PEG-IFN and IFN groups (P<0.05); HBeAg seroconversion rates were similar between PEG-IFN group and IFN group (Χ(2)=0.709, P=0.400). In PEG-IFN and ETV groups, HBeAg seroconversion rates were not associated with age, gender, baseline HBeAg, baseline HBV DNA and baseline ALT. In IFN group, HBeAg seroconversion rates were associated with baseline HBeAg (P=0.048) but not with age, gender, baseline HBV DNA and baseline ALT. In PEG-IFNα-2a group, ROC analysis showed that the sensitivity and specificity of HBeAg seroconversion at 48 weeks were 0.778 and 0.889, respectively, when the decline rate of HBeAg between baseline and week 24 exceeded 97.81%, with the corresponding positive and negative predictive values (PPV and NPV) of 0.778 and 0.889, respectively; the sensitivity and specificity of HBeAg seroconversion at 48 weeks were 0.889 and 0.722, respectively, when the decline rate of HBeAg between week 12 and week 24 was over 42.75%, with the corresponding PPV and NPV of 0.615 and 0.929, respectively.</p><p><b>CONCLUSION</b>Treatments with PEG-IFNα-2a and conventional IFNα for 48 weeks can achieve a higher HBeAg seroconversion rate than ETV, but the latter produces a higher HBV DNA undetectable rate. For PEG-IFNα-2a treatment, the decline rate of HBeAg between baseline and week 24 over 97.81% is the best predicting factor for HBeAg seroconversion at week 48 in CHB patients positive for HBeAg.</p>

The preliminarily investigation of therapeutic effects of mesenchymai stem cells on rat fulminant hepatic failure / 中华传染病杂志

Objective To investigate the therapeutic effects of mesenchymal stem cells (MSC) on rat fulminant hepatic failure (FHF). Methods The rat MSC were separated and purified by adherent culture of whole bone marrow cells. The rat FHF models were established by CCl4 intragastric administration.The rats were divided into experimental group (n=20) and model control group (n=20).And the same dose of saline was administered to rats as normal controls (n=8).Dosage of 1.0 × 106 4',6-diamidino-2-phenylindole (DAPI) labeled MSC were transplanted into rats in experimental group and normal control group through caudal veins,and the same dose of saline was given intravenously in model control group.Part of rats in each group were sacrificed after 7 days and 14 days of injection to evaluate the general condition,survival rate,liver function,tumor necrosis factor (TNF)-α level,liver pathology and MSC homing to the liver between experimental group and model control group.Normal distribution data were compared by independent-sample t test and nonnormal distribution data were analyzed by non-parameter test.ResultsAfter 3 days of injection,the generalcondition of experimental group were better than the model control group. After 7 days of injection,there were 15 and 8 survival rats,the survival rates were statistically different between experimental group and model control group (x2 =4.122,P＜0.05).After 7 days and 14 days of injection,the liver function and TNF-α levels were statistically different between experimental group and model control group (both P ＜0.05),and liver pathology improvement in experimental group was more significant than model control group.DAPI labeled cells increased after transplantation in experimental group, whilefewDAPIlabeledcellswere observedinnormalcontrolgroup.ConclusionsMSC can home to liver of FHF rats after MSC allogeneic transplantation through caudal veins,which can improve liver immunity and liver tissue necroinflammation,and facilitate recovery of liver function.Therefore,it is demonstrated that MSC transplantation has obvious therapeutic effect on rat FHF.

Effect of different therapeutic regimens on serum interleukin-21 levels in patients with chronic hepatitis B / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect serum interleukin-21 (IL-21) levels in patients with chronic hepatitis B receiving different therapeutic regimens.</p><p><b>METHODS</b>A total of 198 patients with inactive chronic hepatitis B were divided into 3 groups according to the therapeutic regimens, namely interferon (IFN)-treated group (IFN group, n∓38), nucleoside analogue-treated group (NA group, n∓72) and untreated group (control group, n∓88). IL-21 and serum hepatitis B virus (HBV) markers were detected in these patients using enzyme-linked immunosorbent assay (ELISA), and the liver function indices were measured with an auto-biochemical analyzer.</p><p><b>RESULTS</b>The serum IL-21 levels in Con and IFN groups were significantly higher than those in NA group (102.29∓14.03, 123.01∓38.26, and 48.10∓7.06 pg/ml, respectively, P<0.05). When all the patients were regrouped according to the status of HBeAg, serum IL-21 level was 114.83∓19.88 pg/ml in HBeAg-negative group (n∓105), significantly higher than that of 61.53∓6.61 pg/ml in HBeAg-positive group (n∓93) (P<0.05). Bivariate correlation analysis showed no significant correlations between IL-21 and liver function indices.</p><p><b>CONCLUSION</b>The immunomodulator IFN might be capable of increasing serum IL-21 levels, while nucleoside analogues can decrease IL-21 level in patients with chronic hepatitis B. HBeAg-negative patients have a significantly higher serum IL-21 level, suggesting that the expression of HBeAg might result in IL-21 depression.</p>

Construction and sequence analysis of recombinant HCV-1b replicon by replacing NS5A region / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct the recombinant HCV-1b replicon by replacing NS5A region using serum samples from patients with chronic hepatitis C (CHC) in South China and explore the biological characteristics of NS5A protein in response to antiviral therapy.</p><p><b>METHODS</b>The on-off plasmid containing the cutting sites of the restriction endonucleases MIu I and Bcl I was designed based on the backbone of robust HCV 1b replicon. The full-length fragments of HCV NS5A were amplified from different CHC patients by RT-PCR and cloned into pMD-18 vector, followed by sequence analysis of amino acid mutation of ISDR, PKRBD, V3 and IRRDR within the NS5A region. If the amplicon obtained contained no MIu I or Bcl I cutting sites, the NS5A fragment was re-amplified using primers containing the cutting sites and inserted into the replicon for replacement.</p><p><b>RESULTS</b>The full-length fragments of NS5A were obtained successfully from CHC patients. The core region of ISDR-V3 of NS5A was replaced in the HCV replicon plasmid and showed correct sequences. The amino acid mutations of ISDR and PKRBD within NS5A were more frequent in patients with sustained viral response (SVR) than those without SVR. A high variability in the amino acid sequence was observed in both IRRDR and V3 regions.</p><p><b>CONCLUSION</b>The plug-in type recombinant HCV replicon for replacement of NS5A region in the virus from CHC patients has been successfully constructed, which provides a basis for further investigation of the biological characteristics of NS5A protein, the mechanisms of interferon-resistance, and antiviral therapy of difficult-to-treat CHC.</p>

Correlation of Pathology and Serology of Fibrosis in Patients with Viral Hepatitis / 中山大学学报(医学科学版)

【Objective】 To study the relationship of pathologic changes and serologic markers of fibrosis in patients with viral hepatitis. 【Me thods】 Liver s pecimens were obtained by percutaneous needle biopsy under color Doppler ultras ound guidance in 299 patients with viral hepatitis. The specimens were stained b y hematoxylin and eosin (HE), Gordon and Sweet's reticulum methods (RT), in orde r to determine the degree and the stage of pathologic changes with microscopy. H yaluronic acid(HA), collagen type Ⅳ(Ⅳ-C) and human precollagen type Ⅲ（HPCⅢ ）as serum fibrous markers were detected by radioimmunoassay. 【Results】 The se rum levels serologic markers were slightly increased in 97 patients with mild ch ronic hepatitis, moderately increased in 126 patients with moderate chronic hepa titis, and significantly increased in 29 severe cases and 47 subjects with cirrh osis. Both the grade of inflammatory activity and the stage of fibrosis were clo sely related to the levels of serum fibrous markers. 【Conclusion】 Chronic vira l hepatitis pathologic feature and levels of serum markers of fibrosis change al ong with clinical process of patients. The combination of liver biopsy and detec tion of serum markers of fibrosis might be highly valuable for the diagnosis.