In 2016, the World Health Organization set an ambitious goal of reducing viral hepatitis-related deaths by 65% by 2030. The key to this goal is to reduce viral hepatitis-related HCC deaths. Liver cancer is the fourth most common malignant tumor and the second leading cause of cancer death in China. The onset of HCC is insidious, and most patients are already in the middle and late stage when diagnosed. Despite the great progress on management of HCC, the therapeutic effect and prognosis of HCC are still unsatisfactory. Therefore, multi-dimensional and comprehensive analysis of the mechanism of liver cancer, improving the early screening, diagnosis and treatment rate of liver cancer are the key points of reducing the harm of liver cancer in China. In recent years, multi-omics studies have been widely applied in the field of liver cancer, providing a basis for the pathogenesis of liver cancer, early detection and diagnosis, development of individual treatment strategies and prognosis assessment. This issue will focus on the application of genomics, proteomics, metabolomics and imaging omics in early screening, diagnosis and treatment of liver cancer.
Carcinoma, Hepatocellular/therapy* ; Early Detection of Cancer/methods* ; Hepatitis, Viral, Human ; Humans ; Liver Neoplasms/therapy* ; Prognosis

OBJECTIVE: This study aimed to investigate DNA sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These DNA sequences are present in the whole DNA extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5'-noncoding region (5'-NCR) homologous DNA sequences could be contained in the extrachromosomal circular DNA (eccDNA) fraction as part of the whole cellular DNA. METHODS: Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccDNA, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed. RESULTS: The PCR tests revealed DNA sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5'-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5'-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the DNA sequences of the 5'-NCR revealed a broad diversity of individual patterns of methylation. CONCLUSIONS The experimental results confirm our assumption that parts of the HCV 5'-NCR genomic RNA sequences are present at the DNA level in the eccDNA fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.
Computational Biology ; DNA Methylation ; DNA, Circular/genetics* ; DNA, Viral/genetics* ; Genome, Human ; Genomics ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/virology* ; Humans ; Leukocytes, Mononuclear/virology* ; Polymerase Chain Reaction ; RNA, Viral/genetics* ; Sequence Alignment

Communicable Disease Control ; methods ; trends ; Disease Eradication ; organization & administration ; Hepatitis, Viral, Human ; epidemiology ; prevention & control ; Humans ; Public Health ; Singapore ; epidemiology

Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV-related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/microg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis.
Aged ; Anemia, Aplastic/*complications ; Carbapenems/therapeutic use ; Chronic Disease ; DNA, Viral/blood ; Epstein-Barr Virus Infections/complications/*diagnosis/pathology ; Female ; Hepatitis/*complications ; Herpesvirus 4, Human/*genetics/isolation & purification ; Humans ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Urinary Tract Infections/drug therapy

OBJECTIVETo investigate the malondialdehyde (MDA) level and paraoxonase-1 (PON-1) activity in the serum and seminal plasma of infertile men with chronic viral hepatitis and their influence on the semen parameters of the patients.

METHODSWe collected serum and semen samples from 42 infertile men, 45 infertile males with chronic viral hepatitis, and 50 healthy fertile men as controls. We measured the MDA level in the serum and seminal plasma by spectrophotometry, detected the PON-1 activity by spectrophotometry, and determined the sperm DNA fragmentation index (DFI) by acridine orange fluorescence staining.

RESULTSThe MDA level was significantly higher but the PON-1 activity remarkably lower in the serum and seminal plasma of the infertile males with chronic viral hepatitis than in the healthy controls and infertile patients (P <0.01 or P <0.05). Total sperm motility and sperm survival rate were significantly lower while the sperm DFI markedly higher in the former than in the latter two groups (P <0.01 or P <0.05). No statistically significant difference was found among the three groups in sperm concentration (P >0.05). The WBC counts in the semen of the infertile and infertile with chronic viral hepatitis groups were significantly higher than that in the health controls (P <0.05). The MDA level and PON-1 activity in the seminal plasma were positively correlated with those in the serum in the infertile males with chronic viral hepatitis (r=0.57 or 0.48, P <0.01).

CONCLUSIONVirus-induced chronic active hepatitis enhances oxidative stress in the reproductive system, aggravates sperm damage, and affects sperm quality parameters.

Adult ; Aryldialkylphosphatase ; analysis ; Case-Control Studies ; DNA Fragmentation ; Fertility ; Hepatitis, Viral, Human ; complications ; Humans ; Infertility, Male ; blood ; Male ; Malondialdehyde ; analysis ; blood ; Oxidative Stress ; Semen ; Sperm Count ; Sperm Motility ; Spermatozoa

BACKGROUND AND AIMS: The precise identification of true inactive hepatitis B carrier is difficult due to frequent fluctuations in Hepatitis B virus (HBV) DNA and serum transaminase levels, needing serial determinations for a period of at least one year. Hence we correlated the hepatitis B surface antigen (HBs Ag) titer of untreated Hepatitis B e Antigen (HBe Ag)-negative patients with their corresponding HBV DNA and alanine aminotransferase (ALT) levels, classified these patients as either inactive carrier or patients in the reactivation phase using the American Association for the Study of Liver Diseases (AASLD) guidelines and finally determined if there was a significant difference in HBs Ag titer between these groups.
METHODS: A cross sectional retrospective study was done. All HBe Ag- negative Chronic hepatitis B (CHB) patients who had their HBs Ag titer, HBV DNA and ALT done at National Kidney and Transplant Institute (NKTI) were obtained and clinical information was abstracted from their case records. A total of 40 patients were included in the study.
RESULTS: The mean HBs Ag titer among untreated HBe Ag negative CHB patients was 3037.04 IU/mL (SD +/- 8718.94 IU/mL). Using Spearman's coefficient of correlation, HBs Ag was found to be directly correlated with HBV DNA (R = 0.821, p = 0 < 0.05) and serum ALT (R = 0.654, p = 0 < 0.05). Moreover, using Mann Whitney T Test, the mean difference in HBs Ag titer between inactive carrier group (mean 103.72 IU/mL, SD +/- 144.25) and reactivation phase group (mean 5690.99 IU/mL, SD +/- 11517.39) was significant (p value = 0 < 0.05).
CONCLUSION: HBs Ag titer was found to be directly correlated with HBV DNA and ALT. To our knowledge, this is the first local study done that supports the concept that HBs Ag titer can provide complementary information in differentiating patient as true inactive carrier from those in the reactivation phase.

Human ; Male ; Female ; Middle Aged ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic ; Alanine Transaminase ; Hepatitis B Virus ; Dna, Viral ; Serum

BACKGROUND/AIMS: It is well-known that patients with chronic liver disease commonly have nutritional deficiency. In the present study, we investigated the differences in malnutrition risk between patients with liver cirrhosis and viral hepatitis carrier. METHODS: Patients with chronic liver disease who have been hospitalized at Konyang University Hospital from May 2012 to April 2013 were analyzed retrospectively. The malnutrition risk was divided into three categories (low, intermediate, and high) according to Konyang University Hospital Malnutrition Screening, which include BMI, serum albumin, total lymphocyte count (TLC), hemoglobin, weight change, appetite, and dysphagia, within 24 hours of hospitalization. RESULTS: Among a total of 460 patients, 313 had liver cirrhosis (LC), and 147 were viral hepatitis carriers. Age (p<0.001), serum albumin level (p<0.001), TLC (p=0.011), hemoglobin (p<0.001) and serum cholesterol level (p=0.005) were significant different between the two groups. However, there were no difference in height, weight, and BMI. The malnutrition risk of the patients with viral hepatitis carrier was significantly lower than that of the patients with LC (p<0.001). In addition, among 313 patients with LC, malnutrition risk of the patients with Child-Pugh class A (n=150) was significantly lower than that of the patients with class B (n=90) or C (n=73) (p<0.001). CONCLUSIONS: Viral hepatitis carrier group had significantly lower malnutrition risk than LC group. The risk of malnutrition in Child-Pugh class A group was significantly lower than that in class B or C group.
Adult ; Aged ; Body Mass Index ; Cholesterol/blood ; Female ; Hemoglobins/analysis ; Hepatitis, Viral, Human/*pathology ; Hospitals, University ; Humans ; Liver Cirrhosis/*pathology ; Lymphocyte Count ; Male ; *Malnutrition ; Middle Aged ; Nutritional Status ; Retrospective Studies ; Risk ; Serum Albumin/analysis ; Severity of Illness Index

OBJECTIVETo explore the pathological and clinical characteristics of children with liver diseases by retrospective study on clinical and liver biopsy pathological data of children with liver diseases.

METHODThis retrospective analysis was performed at Beijing No. 302 Hospital among 3 932 children with liver diseases who visited the hospital from January 2001 to December 2012. The kinds of diseases were compared with the results of 1983-2000.

RESULT(1) Liver biopsy was successful in 99.72% (3 932/3 943) of cases of 2001-2012 group, complications occurred in 31 children only. (2) Of the 3 932 cases, 2 647 (67.32%) had hepatitis , non-hepatotropic viral hepatitis and non viral liver disease were seen in 365 cases (9.28%), and 920 cases (23.4%), respectively. Among 2 647 cases with viral hepatitis, 2 115 were hepatitis B (79.90%), 521 hepatitis C (19.69%), 7 were hepatitis A (0.26%) and 4 hepatitis E (0.15%), respectively. (3) In 2001-2012 group, the degrees of inflammatory activity (>G2) of liver were seen in 9.57% (202/2 111) patients with hepatitis B, while 23.57% (132/560) in 1983-2000 group. There was significant difference between the two groups (χ(2)=80.36, P=0.00 ). (4) Significant difference was observed in the rate of non viral liver disease between 2001-2012 group (23.40%, 920/3 932) and 1983-2000 group (9.61%, 98/1 020) (χ(2)=93.46, P=0.00). In 2001-2012 group, including 46 kinds of diseases, which were significantly higher than those of 1983-2000 group (18 kinds). In 2000-2012, the main causes of diseases were liver degeneration (18.26%, 168/920), drug-induced liver injury (13.59%, 125/920), fatty liver (8.80%, 81/920) and liver glycogen accumulation disease (8.70%, 80/920). While in 1983-2000 group, the main causes were liver degeneration (20.41%, 20/98), fatty liver (16.33%, 16/98), glycogen storage disease (10.20%, 10/98) and myopathy (9.18%, 9/98).

CONCLUSIONLiver biopsy in children is safe and feasible. Hepatitis B virus was ranked first in children with liver diseases in 2001-2012 group. The kinds of non viral hepatic disorders had changed and extended.

Adolescent ; Biopsy, Needle ; Child ; Child, Preschool ; Female ; Hepatitis B ; pathology ; Hepatitis, Viral, Human ; pathology ; Hepatolenticular Degeneration ; epidemiology ; pathology ; Humans ; Infant ; Liver ; pathology ; Liver Diseases ; pathology ; Liver Function Tests ; Male ; Retrospective Studies

OBJECTIVETo systematically evaluate the efficacy and safety of diammonium glycyrrhizinate enteric-coated capsules versus diammonium glycyrrihizinate in patients with chronic viral hepatitis.

METHODSThe Chinese Biomedical Literature Database (CBM on CD-ROM) and the China Academic Journals Full-Text Database (Chinese National Knowledge Infrastructure, CNKI) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of diammonium glycyrrhizinate entetic-coated capsules versus diammonium glycyrrihizinate in treatment (less than 2 months) of chronic viral hepatitis published between 2005 and 2012. A meta-analysis was performed on the selected RCTs to determine the effects on alanine aminotransferase (ALT) normalization, serum levels of ALT, aspartate aminotransferase (AST), total bilirubin (TBil) and albumin, as well as rates of adverse reactions.

RESULTSNine RCTs, involving 687 patients, were included in the meta-analysis. Compared to the patients treated with diammonium glycyrrihizinate, the patient treated with diammonium glycyrrhizinate enteric-coated capsules had a significantly better recovery rate of ALT (relative risk (RR) =4.15, 95% confidence interval (CI):1.55 to 11.15, P less than 0.01) and significantly more robust decreases in ALT (weighted mean difference (WMD) = -32.75, 95% CI:-46.67 to-18.83, P less than 0.01) and AST (WMD = -12.70, 95% CI:-21.13 to-4.27, P less than 0.01). In contrast, the patients treated with diammonium glycyrrihizinate showed more robust improvements in the TBil level (WMD = -0.74, 95% CI:3.98 to 2.49, P =0.653) and albumin (WMD =1.03, 95% CI:-1.03 to 3.09, P =0.326), but the differences did not reach the threshold for statistical significance (P less than 0.05). Only four adverse reactions were reported, all of which were related to the lipid complex nature of the diammonium glycyrrhizin enteric-coated capsules and were mild, including dry mouth, dizziness and mild gastrointestinal discomfort and reactions.

CONCLUSIONDiammonium glycyrrhizinate enteric-coated capsules elicited superior anti-inflammatory and liver protection effects than diammonium glycyrrihizinate, and produced only mild side effects that are tolerable to the patients.

Capsules ; Glycyrrhizic Acid ; administration & dosage ; therapeutic use ; Hepatitis, Chronic ; drug therapy ; Hepatitis, Viral, Human ; drug therapy ; Humans ; Randomized Controlled Trials as Topic

Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.
Antiviral Agents/therapeutic use ; Hepatitis B/drug therapy/pathology/surgery ; Hepatitis C/drug therapy/pathology/surgery ; Hepatitis E/drug therapy/pathology/surgery ; Hepatitis, Viral, Human/drug therapy/pathology/*surgery ; Humans ; *Liver Transplantation ; Recurrence