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ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.
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Objective To investigate the status and molecular epidemiology of hepatitis D virus (HDV) infection in the gathering area of Mongolian population in Inner Mongolia Autonomous Region of China. Methods A total of 230 patients with positive hepatitis B surface antigen (HBsAg) who attended Inner Mongolia International Mongolian Hospital from April 2019 to October 2020 were enrolled, and according to related information, they were divided into hepatitis B+liver cirrhosis group( n =18) and hepatitis B group( n =212). According to HBsAg quantification with a cut-off value of 250 IU/mL, the patients were divided into HBsAg < 250 IU/mL group( n =104) and HBsAg ≥250 IU/mL group( n =126). ELISA was used to detect HDV antibody, and quantitative real-time PCR was used to measure HDV RNA in patients with positive HDV antibody. Genotyping was performed for HDV RNA-positive samples. The chi-square test was used for comparison of categorical data between two groups. Results The positive rate of HDV antibody was 16.09%, and among the patients with positive HDV antibody, the positive rate of HDV RNA was 91.89%. Among the 18 patients with hepatitis B and liver cirrhosis, the positive rate of HDV antibody was 44.44%, and among the patients with positive HDV antibody, the positive rate of HDV RNA was 100%. There were 104 patients with HBsAg < 250 IU/mL, among whom only 3 patients (2.88%) were positive for hepatitis D antibody, and there were 126 patients with HBsAg ≥250 IU/mL, with a positive rate of HDV antibody of 26.98%. Genotype 1 was observed in all the samples that could be genotyped. Conclusion There is a relatively high infection rate of HDV in Inner Mongolia Autonomous Region, especially in patients with HBsAg ≥250 IU/mL or those with liver cirrhosis. It is necessary to strengthen the detection of hepatitis D in HBsAg-positive patients and perform early diagnosis and treatment to prevent the further progression of hepatitis.
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Hepatitis D virus (HDV) infection requires the participation of hepatitis B virus (HBV), which accelerates disease progression after infection and induces a high risk of progression to end-stage liver diseases such as liver cirrhosis and liver cancer. With the gradual increase in the understanding of hepatitis D in the whole society, some therapeutic drugs for hepatitis D have become a research hotspot in recent years, and with the further improvement in clinical testing methods, researchers have started to pay attention to the epidemiological investigation of hepatitis D. Although many studies have been conducted for the specific situation of HDV infection in China, large data deviation is observed due to small cohorts with strong regional features. This article briefly reviews the population, methods, and indicators in the current epidemiological investigation of hepatitis D and discusses related key issues, in order to obtain more accurate epidemiological data, effectively screen out HDV infection, and provide help for early clinical intervention and treatment.
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Hepatocellular carcinoma (HCC) often has an insidious onset, and most patients are in the advanced stage and have lost the best opportunity for treatment at the time of diagnosis, resulting in a poor prognosis. As a multifunctional transcription factor, Yin Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a key role in various tumors. Previous studies have shown that YY1 affects many biological behaviors such as proliferation, apoptosis, migration, and angiogenesis and is closely associated with drug resistance and poor prognosis of HCC. This article reviews the research advances in the role of YY1 in the development and progression of HCC, so as to provide a theoretical basis for the treatment of HCC.
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In November 2018, the U.S. food and drug administration (FDA) issued guidance for the development of drugs for chronic hepatitis B virus infection (draft for comments) (hereinafter referred to as draft for comments), and in April 2022, the FDA issued Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment, which has been updated with some details based on the Draft for Comments. This guidance further emphasizes the importance of HBsAg clearance in clinical trials, and classifies chronic suppressive therapy into two categories, namely noninferiority (NI) (or superiority) test with nucleos(t)ide analogues as control and add-on superiority trial with nucleos(t)ide analogues as control, and as for the latter, HBV DNA is no longer recommended as a primary endpoint of the trial, which poses a huge challenge to the development of innovative drugs targeting HBV DNA. The new finite duration therapy should aim to eliminate HBsAg and reduce virologic relapse and the risk of liver disease progression during treatment cessation. Reduction in HBsAg from baseline is not recommended as a primary endpoint for phase Ⅲ clinical trials, since the correlation between such reduction and clinical response remains unclear. In addition, this guidance also specifies the duration of treatment cessation and treatment consolidation period and the criteria for withdrawal of nucleos(t)ide analogues.
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Objective To investigate the articles on liver diseases published by authors from China (excluding Hong Kong, Macao, and Taiwan regions) in Gastroenterology & Hepatology journals indexed in Science Citation Index Expanded (SCIE) in 2016-2020, to analyze the bibliographic and citation data of these articles, and to understand the contribution and impact of Chinese scholars in the field of liver disease research in recent years. Methods The data for bibliometric analysis came from the SCIE database and Journal Citation Reports (JCR). The SCIE database was searched for the journal articles published in JCR Gastroenterology & Hepatology journals in 2016-2020, with a title or abstract containing "Liver", "Hepatocellular", "Hepatitis", "Cirrhosis", or "Hepatic" and a publication type of Article. Clinical guidelines were excluded, and the records with the corresponding author's affiliation containing institutions in China (excluding Hong Kong, Macao, and Taiwan regions) were screened out. R package bibliometrix was used to calculate the frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals in 2016-2020, and R package DescTools was used to perform the Cochran-Armitage trend test to observe the change in composition ratio. Results In the Q1 Gastroenterology & Hepatology journals in 2016-2020, liver disease studies published by Chinese authors accounted for 9.5%. In recent years, the proportion of liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals continues to increase from 6.0% to 12.2% ( P < 0.001). Among the liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals, 79.7% were funded by National Natural Science Foundation of China, and there was no significant change in the proportion of studies funded by National Natural Science Foundation of China and published by Chinese authors in each partition of Gastroenterology & Hepatology journals in 2016-2020. The frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals showed that liver disease studies published by Chinese authors had a high impact in both domestic and international academic communities. Conclusion In recent years, there has been a constant increase in the number of liver disease studies published by Chinese authors in high-impact Gastroenterology & Hepatology journals indexed in SCIE, and most of these studies have been funded by National Natural Science Foundation of China. The liver disease studies published by Chinese authors in Gastroenterology & Hepatology journals have been widely recognized by domestic and international academic communities.
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The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.
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The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.
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ObjectiveTo investigate the tolerance, pharmacokinetics, and antiviral activity of coblopasvir hydrochloride capsules in patients with hepatitis C. MethodsA total of 36 patients with hepatitis C who were admitted to The First Hospital of Jilin University from November 2016 to January 2017 were enrolled as subjects, and four dose groups (30 mg, 60 mg, 90 mg, and 120 mg) and one placebo group were established. The subjects were administered once daily for 3 consecutive days; tolerance was evaluated on D2 and D6, and follow-up was performed on D8 and D10. The subjects were enrolled based on single dose escalation, and a multiple-dose study was conducted under the premise of good tolerance to single dose. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of coblopasvir hydrochloride in human body, and WinNonlin 6.4 software was used to calculate main pharmacokinetic parameters. HCV RNA load was used to evaluate antiviral activity at different time points; a one-way analysis of variance was used for comparison between multiple groups, and the LSD t-test was used for further comparison between two groups. ResultsAfter coblopasvir hydrochloride capsules were administered orally once a day at a dose of 30-120 mg, the plasma concentration and exposure of coblopasvir hydrochloride increased with the increase in dose. There were no significant differences in plasma concentration and exposure between multiple-dose administration and single-dose administration in a fasting state, without accumulation in human body. After the oral administration of coblopasvir hydrochloride capsules once a day, the subjects with HCV genotype 1b had a reduction in HCV RNA load since baseline, with the lowest level at 120 hours, and there was a significant difference in antiviral activity between different dose groups (F=14.621, P＜0.000 1), among which the 60 mg group had a significantly greater reduction than the 30 mg group (P=0.025), while there was no significant difference between the 60 mg group and the 90/120 mg group (P＞0.05). There was no significant difference in HCV RNA load between different groups of patients with HCV genotype 2a (P＞0.05). Of all 36 subjects, 20 reported 34 cases of treatment-emergent adverse events, among which 19 cases were associated with coblopasvir hydrochloride, and no significant adverse events or serious adverse events were observed. ConclusionOral administration of coblopasvir hydrochloride capsules in a fasting state at a dose of 30-120 mg/d (for 3 consecutive days) has good safety and antiviral activity. Therefore, it has good application prospect in the treatment of HCV infection and provides a basis for dose selection in phrase 2 study.
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Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with unknown etiology, and patients with poor response to ursodeoxycholic acid and obeticholic acid may eventually progress to liver cirrhosis and even liver failure. Liver transplantation is the only effective treatment method for PBC at present. This article elaborates on liver transplantation, survival time after liver transplantation, complications, recurrence of PBC after liver transplantation, and prospects and challenges of liver transplantation in patients with PBC, so as to provide a reference for clinical outcome and treatment after liver transplantation for PBC.
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SIGIRR, a member of the interleukin 1 receptor superfamily, is also known as a single immunoglobulin (Ig)-related receptor, which is believed to play a key role in the development of inflammation and the regulation of anti-inflammatory effects. Some studies believe that the abnormal down-regulation of SIGIRR can lead to intestinal inflammation, pyelonephritis, systemic lupus erythematosus and other diseases, but it can promote tumor growth and potentially cause anti-tumor immune damage when its genes are overexpressed. Therefore, the role of SIGIRR in disease occurrence and development is considered a double-edged sword. At present, the detailed molecular mechanism of SIGIRR′s biological role is not fully understood. This article reviews the functions of SIGIRR in the occurrence and development of immune-related diseases and immune regulation, as well as related cell signaling pathways, which have been discovered and confirmed.
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ObjectiveTo investigate the effect of direct-acting antiviral (DAA) on the recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative treatment. MethodsPubMed, Web of Science, Cochrane Library, CNKI, CBM, Wanfang Data, and VIP were searched for the clinical studies of DAA and the recurrence of HCV-related HCC published up to April 2020. Stata 14.0 software was used to perform the meta-analysis. The Cochran Q test was used to evaluate heterogeneity between studies; the fixed effects model was used for non-heterogeneous data, and the random effects model was used for heterogeneous data. The Egger regression method or the Begg rank correlation method was used to evaluate the presence or absence of publication bias. ResultsA total of 10 articles (11 studies) were included in our study, among which 8 articles (9 studies) compared the effect of DAA versus the absence of anti-HCV therapy on the recurrence of HCC after curative treatment. There were 991 patients in DAA group and 808 patients in untreated group. The results of the meta-analysis showed that DAA reduced the recurrence rate of HCC after curative treatment in patients with HCV infection (hazard ratio ［HR］=0.42, 95% confidence interval ［CI］: 0.28?0.36, P＜0.001). Three articles compared the effect of DAA versus interferon for the treatment of hepatitis C on the recurrence of HCC after curative treatment, with 267 patients in DAA group and 212 in interferon group, and the results of the meta-analysis showed that DAA and interferon had a similar effect on the recurrence rate of HCV-related HCC (HR=0.85, 95% CI: 0.64-1.15, P=0.298). ConclusionBoth interferon and DAA can significantly reduce the recurrence risk of HCV-related HCC after curative treatment, with no significant difference between them.
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With the appearance of direct-acting antivirals (DAAs), breakthroughs have been achieved in the antiviral therapy for hepatitis C and hepatitis C patients can be cured completely. Due to the insidious onset of hepatitis C, most patients do not know their own conditions, and thus expanding diagnosis and treatment through screening is the key to the elimination of hepatitis C. However, hepatitis C virus is distributed widely and unevenly in the world, which results in difficulties in the screening and diagnosis of hepatitis C. This article introduces the current economic research on hepatitis C screening, analyzes the factors affecting the cost-effectiveness of hepatitis C screening, and shares the strategies and advances for hepatitis C elimination in other countries, so as to provide a reference for eliminating hepatitis C in China.
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ObjectiveTo investigate the clinical features of liver function and coagulation function in patients with Alongshan virus (ALSV) infection. MethodsClinical data were collected from 27 patients with ALSV infection who were admitted to Inner Mongolia General Forestry Hospital from May 2018 to September 2019, among whom there were 18 male patients and 9 female patients. Related data were extracted, and a database of relevant case reports was established. The descriptive epidemiological method was used to analyze the clinical features of liver function and coagulation markers, and the features of liver injury caused by ALSV infection were analyzed. ResultsFor the 27 patients, the abnormal rates of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), cholinesterase, and total bile acid were 25.9%, 33.3%, 25.9%, 40.7%, 8%, and 8%, respectively; among the 27 patients, 4 (14.8%) had an ALT level of ＞2×upper limit of normal (ULN), 3 (11.1%) had an AST level of ＞2×ULN, 1 (3.7%) had an ALP level of ＞2×ULN, and 5 (18.5%) had a GGT level of ＞2×ULN. Among the 27 patients, 25 (17 male patients and 8 female patients) had the results of bilirubin test, among whom 1 had a reduction in total bilirubin (TBil) (3.30 μmol/L) and 3 had an increase in TBil (23.7 μmol/L, 26.2 μmol/L, and 32 μmol/L, respectively). The abnormal rates of the coagulation markers international normalized ratio, activated partial thromboplastin time, and fibrinogen were 3.7%, 11.1%, and 22.2%, respectively. ConclusionThere is a certain degree of liver injury in patients with ALSV infection, generally with mild symptoms.
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ObjectiveTo investigate the serum level of ceruloplasmin in patients with different stages and etiologies of liver diseases. MethodsA total of 1077 patients with liver diseases who were hospitalized in Department of Hepatology, The First Hospital of Jilin University, from January 2012 to January 2018 were enrolled, and the serum level of ceruloplasmin was analyzed for the patients with different liver diseases. The Kruskal-Wallis H test was used to compare the level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and a Spearman correlation analysis was used to investigate the correlation of ceruloplasmin with other biomarkers. ResultsIn the Wilson’s disease group, 97.6% (41/42) of the patients had a serum ceruloplasmin level of ＜0.2 g/L and 881% (37/42) had a level of ＜0.1 g/L. In the non-Wilson’s disease group, 24.3% (251/1035) of the patients had a ceruloplasmin level of ＜0.2 g/L and 0.2% had a level of ＜0.1 g/L. There was a significant difference in the serum level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and the patients with chronic viral hepatitis, severe viral hepatitis, and viral hepatitis cirrhosis had a significantly lower level than those with acute viral hepatitis and virus-related liver cancer (P=0005, P＜0.001, P=0.001, P=0.027, P＜0.001, and P=0.001). In the patients without Wilson’s disease, serum ceruloplasmin was positively correlated with albumin and prealbumin (r=0.068 and 0.091, both P＜0.05) and was negatively correlated with prothrombin time (r=-0.297, P＜0.05). ConclusionCeruloplasmin often decreases significantly in patients with Wilson’s disease, with a slight reduction in patients with other types of liver diseases. For these patients, it should be determined whether the reduction in ceruloplasmin is caused by hepatocyte injury or the presence of Wilson’s disease.
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Presently, nonalcoholic fatty liver disease has become the most common pathogenic factor of chronic liver disease worldwide that can lead to the occurrence of hepatocellular carcinoma (HCC). Lipid metabolism in cancer cells is closely related to tumorgenesis, invasion and metastasis, and thus acts as one of the hallmark of cancer cells. Lipolipomics is an important branch of metabolomics, which has been adapted recently in the study of HCC for analysis of the structure and function of lipid components by chromatography and mass spectrometry. Fatty acids, glycerides, glycerophospholipids, sphingolipids, and sterol are significantly different in HCC tissues or serum. Therefore, it contributes to the diagnosis, determination of prognosis, mechanistic study and targeted therapy of HCC.
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Hepatocellular carcinoma (HCC) has a high incidence and mortality rate in China, and is the worst-than-expected cancer management disease in all provinces of the country. In recent years, systemic drug therapy for HCC has developed rapidly, especially molecular targeted drugs and immune checkpoint blocker being the most prominent. Molecular targeted drugs and immune checkpoint blocker have achieved some progress in the treatment of advanced HCC, but they still have many problems and challenges. This paper briefly introduces the latest advances of drug therapy for advanced HCC.
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Objective To investigate the clinical features of type 1 autoimmune pancreatitis(AIP),and to deepen the understanding of this disease,reduce false positive rate,and enhance people′s awareness of this disease. Methods A retrospective analysis was performed for the clinical data of 13 patients with type 1 AIP who were admitted to The First Hospital of Jilin University from January 2012 to December 2016,including general status,clinical manifestations,laboratory serological examination,imaging findings,histopathological findings, treatment,and prognosis. Results Of all 13 patients,there were 9 male and 4 female patients with a mean age of 60.08 ± 9.47 years. Ma-jor clinical manifestations included jaundice(69.2%),abdominal pain(61.5%),and weight loss(61.5%). The most common organ in-volved was bile duct(46.2%),and 30.8% of the patients had sclerosing cholangitis. Of all patients,23.1% had diabetes. As for serolog-ical markers,92.30% patients had more than 2 times increase in IgG4,and 7.69% had 1-2 times increase in IgG4;53.85% patients had an increase in CA19-9;69.23% patients had an increase in total bilirubin;more than two thirds of the patients had an increase in amin-otransferases or gamma-glutamyl transpeptidase. As for imaging findings,53.8% patients had diffuse enlargement of the pancreas on CT, 46.2% had focal enlargement of the pancreas,and 46.2% patients had low-density cyst-like shadow in pancreatic lesions. Pathological examination showed fibrous connective tissue proliferation with infiltration of lymphocytes and plasma cells. All patients were given standard glucocorticoid therapy(initial dose of prednisone:30-40 mg/d)and the remission rate of glucocorticoid therapy was 100%. The follow-up time was 12 months,and one patient experienced multiple recurrences in the course of the disease. Conclusion Type 1 AIP is the local manifestation of IgG4-associated disease in the pancreas,which often occurs in middle-aged and elderly men,and most patients are com-plicated by extrapancreatic lesions. Glucocorticoid therapy is effective and most patients have good prognosis. Recurrence often occurs in the case of no standard or long-term glucocorticoid therapy.
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The elimination of hepatitis B virus is not straightforward in chronic hepatitis B patients. A prolonged treatment and chance of recurrence after stopping the drug is a matter of concern for majority of specialists and patients. The traditional monitoring indicators and new serological markers for strengthening the determination of standard antiviral treatment of hepatitis B virus (HBV) has an important meaning towards clinical treatment and treatment protocol guiding regulations.
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Objective@#The aim was to investigate the genotype distribution of two major epitopes of large surface protein (PreS1) of hepatitis B in Chinese patients and to explore the association between the genotypes of these two epitopes, and to determine whether PreS1 full-length genotype could be revealed according to the polypeptide sequence of key epitopes. @*Methods@#HBV DNA was extracted from the serum of patients for PCR amplification. 278 samples amplified successfully were sequenced and compared with the known HBV sequences in Genbank to determine the two key epitopes of HBV PreS1 genotype (amino acid epitope 21-47 and 94-117, abbreviated as P21 and P94) and PreS1 full-length genotypes. The correlation among three genotyping approaches was analyzed by Cohen’s kappa coefficient to verify the consistency between the key-epitope genotyping and the full-length preS1 genotyping. @*Results@#232 samples were successfully sequenced. The genotyping based on the kind of P21 epitope protein sequence, 201 cases for genotype C, 23 cases for genotype B and 8 cases for uncertain genotypes and genotyping based on the form of P94 epitope protein sequence, 199 cases for genotype C, 25 cases for genotype B and 8 cases for indeterminate genotypes. Lastly, the genotyping based on sequence of the full-length PreS1 sequence, 207 and 25 cases for genotype C and B. P21 or P94 epitope genotyping and PreS1 full length genotyping were highly consistent, respectively, 96.55% and 96.12%, and the two epitopes (P21and P94) genotyping have parallel consistency (93.10%). @*Conclusion@#In this study, an innovatively genotyping method based on the amino acid sequence of key epitopes was proposed. The genotypes of HBV in china were mainly B and C genotypes, and the genotypes of key conserved epitopes of HBV PreS1 were highly consistent with the full-length genotyping ( > 96%). Moreover, genotyping with one or two key epitopes can be used in place of the full-length genotyping.