A hiddenly high hepatitis C virus related liver disease burden among Chinese patients with non-liver disease complaints: A hospital based study from 2013 to 2017

Objective:To determine the frequency of anti-HCV antibody positivity in patients with non-liver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status.Methods:A hospital based survey of non-liver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1. were the patients adequately advised of the implication of anti-HCV positive finding; 2. to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists.Results:A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive (0.94%). However, only 45.10% (1 253/2 778) of the anti-HCV antibody (+) patients were referred to hepatologists and received HCV RNA test. In addition, 34.10% (312/915) and 1.42% (13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma (HCC), respectively. Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases. Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines. Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection.Conclusions:Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.

A hiddenly high hepatitis C virus related liver disease burden among Chinese patients with non-liver disease complaints: A hospital based study from 2013 to 2017

Objective: To determine the frequency of anti-HCV antibody positivity in patients with non-liver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status. Methods: A hospital based survey of non-liver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1. were the patients adequately advised of the implication of anti-HCV positive finding; 2. to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists. Results: A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive (0.94%). However, only 45.10% (1 253/2 778) of the anti-HCV antibody (+) patients were referred to hepatologists and received HCV RNA test. In addition, 34.10% (312/915) and 1.42% (13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma (HCC), respectively. Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases. Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines. Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection. Conclusions: Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.

Depression and anxiety caused by pegylated interferon treatment in patients with chronic hepatitis B and the therapeutic effects of escitalopram and alprazolam / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam.</p><p><b>METHODS</b>A total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments.</p><p><b>RESULTS</b>In the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010).</p><p><b>CONCLUSION</b>Psychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.</p>

Entecavir combined with Fufang Biejia Ruangan tablet in treatment of chronic hepatitis B patients with liver fibrosis: 96-week efficacy analyses / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis.</p><p><b>METHODS</b>A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging.</p><p><b>RESULTS</b>Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate.</p><p><b>CONCLUSION</b>The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.</p>

Relationship between single nucleotide polymorphisms in IL28B gene and response to interferon treatment in chronic hepatitis B patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship between the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 in IL28B gene and the response to interferon treatment in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B patients.</p><p><b>METHODS</b>Peripheral blood samples were collected from 82 HBeAg-positive patients with chronic hepatitis B receiving interferon treatment, including 38 with favorable response to the treatment and 44 without response. IL28B gene was amplified from the chromosomal DNA, and rs8099917 SNP was genotyped based on PCR-RLFP and rs12979860 SNP by sequencing.</p><p><b>RESULTS</b>In the responsive patients, the distribution frequencies of TT and TG+GG genotypes and allele G in SNPrs8099917 were 81.6% (31/38), 18.4% (7/38), and 9.2% (7/76), as compared to the frequencies of 97.7% (43/44), 2.3% (1/44), and 1.1% (1/88) in nonresponsive patients, respectively. The frequencies showed significant differences between the responsive and nonresponsive patients (P=0.014 for genotypes and P=0.025 for allele G). The distribution frequencies of CT genotypes and allele T in SNPrs12979860 showed no differences between the responsive and nonresponsive patients (P<0.05).</p><p><b>CONCLUSION</b>rs8099917 SNP is probably associated with the response to interferon treatment in HBeAg-positive patients with chronic hepatitis B, and Allele G may be predictive of the treatment success.</p>

Preparation of human anti-HBs from volunteers with hepatitis B vaccine boost vaccination by modified B-cell immortalization technique / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish immortalized B lymphoblast cell lines (B-LCLs) from healthy anti-HBs antibody (anti-HBs)-positive volunteers and screen for human anti-HBs and the antibody-secreting cells.</p><p><b>METHODS</b>The peripheral blood mononuclear cells (PBMC) isolated from 3 healthy volunteers positive for anti-HBs with hepatitis B vaccine boost vaccination were infected with Epstein-Barr virus (EBV) and incubated in the presence of CpG DNA motifs and cyclosporin A (CyA). The anti-HBs in the culture supernatant of the immortalized B-cells was quantified by Architect anti-HBs assay with chemiluminescent microparticle technique. Immunocytochemistry was performed to identify the differentiation of the cell clones expressing anti-HBs.</p><p><b>RESULTS</b>Immortalized B-cell culture was successfully established from the cell clones secreting anti-HBs with EBV infection and CpG DNA stimulation. The titer of anti-HBs in the culture supernatant was at its peak at 3 weeks of cell culture and then decreased gradually. At 3 months of cell culture, the cells still retained the capacity of anti-HBs production as verified by the results of immunocytochemistry for CD20 and CD138.</p><p><b>CONCLUSION</b>Immortalized B-cell culture secreting anti-HBs from volunteers receiving boost hepatitis B vaccination has been successfully established by modified EBV immortalization technique.</p>

Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China.</p><p><b>METHODS</b>Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations.</p><p><b>RESULTS</b>Amongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes.</p><p><b>CONCLUSIONS</b>The MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.</p>

A novel method for hepatitis C virus genotyping using RT-PCR reverse dot blot hybridization technique / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop a rapid and specific method for hepatitis C virus ( HCV) genotyping using reverse dot blot hybridization technique and investigate the distribution of HCV genotypes and subtypes in Guangdong.</p><p><b>METHODS</b>The primers and the probes targeting the 5'untranslated region (5'UTR) and core region of HCV genotypes 1b, 2a, 3a, 3b and 6a were designed, and the RT-PCR reverse dot blot hybridization (PCR-RDH) method for HCV genotyping was established. A total of 115 patients with hepatitis C were genotyped using this method, and 38 of them were also genotyped by sequencing and phylogenetic analysis to evaluate the accuracy and specificity of the method.</p><p><b>RESULTS</b>Of the 115 patients, 111 were successfully genotyped to be 1b, 2a, 3a, 3b, 6a and mix-infection of 1b/2a at frequencies of 56.8%, 8.1 %, 3.6%, 5.4%, 25.2% and 0.9% respectively, and all the 15 healthy control samples showed negative results. The accuracy and reliability of the genotyping method of PCR-RDH was confirmed in 38 cases by amplification of HCV core and NS5B regions followed by DNA sequencing and phylogenetic analysis.</p><p><b>CONCLUSION</b>This method for HCV genotyping, with high reliability and specificity, is suitable for clinical and epidemiological investigations. The prevalence of HCV genotypes 1b and 2a decreases while 1b remains the dominant genotype in Guangdong, where the prevalence of 6a significantly increases as compared with that 10 years ago.</p>

Influence of chronic HBV infection in the husband on the outcome of IVF-ET treatment / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the outcome of in vitro fertilization and embryo transfer (IVF-ET) in couples with the husband positive for chronic infection of hepatitis B virus (HBV).</p><p><b>METHODS</b>This study involved 102 infertile couples receiving IVF-ET with the husbands(but not the wives) positive for hepatitis B surface antigen (HBsAg), and another 204 couples negative for HBsAg receiving the treatment served as the control group. The cumulative embryo score, fertilization rate, cleavage rate, rate of good quality embryos, implantation rate, clinical pregnancy rate, first trimester and late miscarriage rates, delivery rate, and neonatal malformation rate were recorded and compared between the two groups.</p><p><b>RESULTS</b>Between the HBsAg-positive and the control groups, the cumulative embryo score (52.8-/+18.7 vs 55.4-/+16.9), insemination rate (66.9% vs 66.1%), cleavage rate (97.6% vs 97.2%), rate of good quality embryos (34.0% vs 37.1%), implantation rate (40.9% vs 34.6%), clinical pregnancy rate (56.9% vs 50%), first trimester miscarriage rate (6.9% vs 5.9%) and late pregnancy miscarriage rate (8.6% vs 4.9%), delivery rate (40.2% vs 43.6%) and neonatal malformation rate (0 vs 0) were all similar (P>0.05;).</p><p><b>CONCLUSION</b>Chronic HBV infection in the husband might not affect the outcome of IVF-ET treatment.</p>

Therapy effect of lamivudine combination with alpha interferon on patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the short-term therapeutic efficacy and safety of lamivudine (LAM) combining with alpha interferon (IFNalpha) on patients with chronic hepatitis B.</p><p><b>METHODS</b>90 chronic hepatitis B patients with HBV DNA and HBeAg positive were subdivided by 1:1:1 proportion into three groups: (1) LAM+IFN group: 6 months therapy of IFNalpha plus lamivudine followed by 6 months of lamivudine; (2) LAM group: lamivudine alone for 12 months; (3)IFN group: IFNalpha alone for 6 months.</p><p><b>RESULTS</b>At the end of treatment, the HBV DNA undetectable rate in LAM+IFN group (90.0%) was much higher than that in LAM group (80.0%) and IFN group (46.7%) (chi2 = 13.017, P < 0.001). ALT normalization occurred 90.0%, 80.0%, and 53.3% in LAM+IFN group, LAM group, and IFN group, respectively (chi2 = 9.932, P = 0.002). HBeAg/anti-HBe seroconversion rates achieved 46.7%, 13.3%, and 33.3% in LAM+IFN group, LAM group, and IFN group, respectively (chi2 = 7.937, P = 0.005). YMDD mutation was not detected in serum samples from LAM+IFN group patients.</p><p><b>CONCLUSIONS</b>LAM+IFN therapy for chronic hepatitis B is tolerated and more effective than IFN monotherapy in inhibiting viral replication and getting ALT normalization. The HBeAg/anti-HBe seroconversion rate with LAM+IFN therapy is higher than that with lamivudine monotherapy. LAM+IFN combination therapy seems to inhibit or postpone YMDD variants appearing in patients with chronic hepatitis B.</p>