BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of d...BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of direct-acting antiviral(DAA)treatment in HCV-infected patients.METHODS The study included consecutive 9457 women and 9529 men,treated with DAA for chronic HCV infection from July 2015 to the end of 2023 whose data were collected in the nationwide multicenter retrospective Epiter-2 project.Women were divided into pre-menopausal(15-44 years),menopausal(45-55 years)and post-menopausal(>55 years)and compared with age-matched men.RESULTS Regardless of age,women had a significantly lower body mass index,prevalence of genotype 3 infection and proportion of cirrhosis compared to men.Psychiatric disorders(except depression),hepatitis B virus and human immunodeficiency virus co-infections,as well as alcohol and drug addiction,were significantly less common in women than in men in all age groups.The sustained virologic response was significantly higher in women compared to men in each age group and amounted to 98.4%and 96.6%,respectively(P<0.001).Independent predictors of treatment failure in women were genotype 3 infection,cirrhosis and postmenopausal age.Mild adverse events were reported significantly more often by women,regardless of age with the highest percentage in the postmenopausal group.CONCLUSION DAA treatment is more effective in women than in men,regardless of age,but in postmenopausal women,the effectiveness is relatively the lowest.展开更多
The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and ...The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and methods: Our study population consisted of all volunteer blood donors who had donated during a 2-year period from 1 January 2019 to 31 December 2020. Samples were taken from patients with no contraindications and serological tests were performed using ELISA tests. HBsAg, HCV-Ac and HIV serology were tested. All samples reactive for HIV, HBV and HCV were retested for confirmation using a second enzyme-linked immunosorbent assay. A result was considered positive if both the first and second tests were positive. Results: In two years, the Ouahigouya BSDD recorded 9726 donations, including 7983 new donors and 1743 former donors. The average age of donors was 25.59 years, with a sex ratio of 3.4. The seroprevalence of HBV, HCV and HIV was 7.31%, 3.10% and 2.12% respectively. HBV-HCV co-infection was found in 0.32% of cases, HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infection were found in 0.25%, 0.09% and 0.04% respectively. Conclusion: The seroprevalence of viral hepatitis B and C remains high among volunteer blood donors in Ouahigouya, although a decline in seroprevalence appears to be on the horizon.展开更多
To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-ter...To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.展开更多
Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher ...Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.展开更多
Objective To investigate chronic hepatitis C virus(HCV)infection's effect on gestational liver function,pregnancy and delivery complications,and neonatal development.Methods A total of 157 HCV antibody-positive(an...Objective To investigate chronic hepatitis C virus(HCV)infection's effect on gestational liver function,pregnancy and delivery complications,and neonatal development.Methods A total of 157 HCV antibody-positive(anti-HCV[+])and HCV RNA(+)patients(Group C)and121 anti-HCV(+)and HCV RNA(-)patients(Group B)were included as study participants,while 142 antiHCV(-)and HCV RNA(-)patients(Group A)were the control group.Data on biochemical indices during pregnancy,pregnancy complications,delivery-related information,and neonatal complications were also collected.Results Elevated alanine aminotransferase(ALT)rates in Group C during early,middle,and late pregnancy were 59.87%,43.95%,and 42.04%,respectively—significantly higher than Groups B(26.45%,15.70%,10.74%)and A(23.94%,19.01%,6.34%)(P<0.05).Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages(P<0.05).No significant differences were found in neonatal malformation rates across groups(P>0.05).However,neonatal jaundice incidence was significantly greater in Group C(75.16%)compared to Groups A(42.25%)and B(57.02%)(χ^(2)=33.552,P<0.001).HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice(OR=2.111,95%CI 1.242–3.588,P=0.006).Conclusions Chronic HCV infection can affect the liver function of pregnant women,but does not increase the pregnancy or delivery complication risks.HCV RNA(+)is an independent risk factor for neonatal jaundice.展开更多
BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imagi...BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.AIM To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.METHODS We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019.We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging.Liver imaging findings(hepatic steatosis,increased echogenicity,cirrhosis,and chronic liver disease)were further evaluated for their diagnostic performance in detecting fibrosis(≥F2,≥F3,≥F4)and steatosis(≥S1,≥S2,≥S3).RESULTS Of 959 HCV patients who underwent TE,651 had liver imaging.Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings(P=0.0050),hepatic steatosis(P<0.0001),and increased echogenicity(P<0.0001).Higher liver stiffness measurement values were also noted in those with abnormal liver(P<0.0001)and increased echogenicity(P=0.0026).Steatosis severity correlated with hepatic steatosis(r=0.195,P<0.001)and increased echogenicity(r=0.209,P<0.001).For fibrosis detection,abnormal liver imaging had moderate sensitivity(81.7%)and specificity(70.4%)for cirrhosis(≥F4),while cirrhosis on imaging had high specificity(99.2%)but low sensitivity(18.3%).Increased echogenicity showed high specificity(92.8%)but low sensitivity(20.9%)for steatosis detection.CONCLUSION Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity.Integrating TE with imaging may improve evaluation in patients with HCV.展开更多
BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist f...BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist for diagnosing chronic HCV infection.Though beneficial,invasive procedures can cause morbidity and inadequate representation of the overall degree of fibrosis.Due to these reasons,non-invasive liver fibrosis biomarkers are becoming more prevalent to diagnose and track liver fibrosis without a liver biopsy.These biomarkers can detect liver fibrosis early,improving treatment and preventing cirrhosis and liver failure.Micro ribonucleic acid(MiRNA)dysregulation causes and worsens several diseases including liver disease.MiRNAs can facilitate the diagnosis of liver fibrosis and serve as a predictive tool to enhance patient care by minimizing invasive procedures and enabling more efficient and prompt therapy.AIM To investigate the diagnostic effectiveness of several miRNAs(miRNA-122,miRNA-21,miRNA-199a,miRNA-155)in assessing the liver fibrosis severity in untreated HCV patients from the Indian Punjab population.We seek to identify the intricate diagnostic relationship of miRNAs with the extent of fibrosis among individuals with HCV.METHODS We considered 100 persons determined as HCV infected by a quantitative Real-Time Polymerase Chain Reaction examination.We employed statistical as well as probabilistic tools to ascertain the diagnostic validity of miRNAs for determining the liver fibrosis stages.We employed Bayesian Networks,to introduce a unique diagnostic paradigm for miRNAs that can be adopted as benchmark to evaluate the liver fibrosis severity in HCV cases.RESULTS We found that miRNAs(miR-122,miR-155 and miR-21)showed significant upregulation when compared with control and according to severity of fibrosis(P≤0.05).The area under the curve for miR-122,miR-155,miR-21 and miR-199a in HCV group in relation to Liver Stiffness Measurement was calculated as 0.889,0.933,0.912 and 0.035 respectively.MiR-199a was downregulated according to degree of fibrosis.CONCLUSION Depending on the diagnostic accuracy,we have concluded that miR-122,miR-155 and miR-21 are reliable markers to detect fibrosis in Hepatitis C patients.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infect...BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.展开更多
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the hig...The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.展开更多
AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C:...AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.展开更多
BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implicati...BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implications for this disease.METHODS Based on the enrichment of 23 immune signatures,we identified two immunespecific subtypes(Imm-H and Imm-L)of HBV+HCC by unsupervised clustering.We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.RESULTS Compared to Imm-L,Imm-H displayed stronger immunity,more stromal components,lower tumor purity,lower stemness and intratumor heterogeneity,lower-level copy number alterations,higher global methylation level,and better overall and disease-free survival prognosis.Besides immune-related pathways,stromal pathways(ECM receptor interaction,focal adhesion,and regulation of actin cytoskeleton)and neuro-related pathways(neuroactive ligand-receptor interaction,and prion diseases)were more highly enriched in Imm-H than in Imm-L.We identified nine proteins differentially expressed between Imm-H and Imm-L,of which MYH11,PDCD4,Dvl3,and Syk were upregulated in Imm-H,while PCNA,Acetyl-a-Tubulin-Lys40,ER-α_pS118,Cyclin E2,andβ-Catenin were upregulated in Imm-L.CONCLUSION Our data suggest that“hot”tumors have a better prognosis than“cold”tumors in HBV+HCC and that“hot”tumors respond better to immunotherapy.展开更多
Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis...Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.展开更多
Delving into the immunological crossroads of liver diseases,this editorial explores the dynamic interplay between hepatitis C virus(HCV)and autoimmune hepatitis(AIH).While HCV primarily manifests as a viral infection ...Delving into the immunological crossroads of liver diseases,this editorial explores the dynamic interplay between hepatitis C virus(HCV)and autoimmune hepatitis(AIH).While HCV primarily manifests as a viral infection impacting the liver,previous studies unveil a captivating connection between HCV and the emergence of AIH.The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH.Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection,hinting at a potential overlap between viral and autoimmune liver diseases.Navigating the intricate terrain of viral replication,immune response dynamics,and genetic predisposition,this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH.In this immunological crossroads,we aim to unearth insights into the complex interplay,using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.展开更多
BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of...BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.CONCLUSION Although,studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease,HCC,and liver-related death,there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3.Only cirrhosis and age have demonstrated an association;however,the number of studies is very small,and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.展开更多
Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(W...Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.展开更多
BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV t...BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.展开更多
BACKGROUND Chronic hepatitis C virus(HCV)has been associated with hepatic and extrahe-patic malignancies.Limited studies have shown an association between colorectal adenomas and HCV populations.AIM To study the preva...BACKGROUND Chronic hepatitis C virus(HCV)has been associated with hepatic and extrahe-patic malignancies.Limited studies have shown an association between colorectal adenomas and HCV populations.AIM To study the prevalence of colorectal adenomas in patients with HCV compared to the general population and to evaluate if it is an independent risk factor for colorectal adenomas.METHODS Patients were divided into HCV and non-HCV based on their HCV RNA titers.Patients with alcoholic liver disease,hepatitis B infection,and inflammatory bowel disease were excluded.Continuous variables were analyzed using the Mann-Whitney U test,and categorical variables usingχ^(2) with P<0.05 were considered statistically significant.The significant covariates(independent variables)were matched in both groups by propensity score matching,followed by multivariate regression analysis.RESULTS Of the 415 patients screened,109 HCV patients and 97 non-HCV patients with colonoscopy results were included in the study.HCV patients were older,had a smoking history,had less frequent aspirin use,and had a lower body mass index(BMI)(P<0.05).The HCV cohort had a significantly increased number of patients with adenomas(adenoma detection rate of 53.2%vs 34%.P=0.006).We performed a propensity-matched multivariate analysis where HCV infection was significantly associated with colorectal adenoma(OR:2.070,P=0.019).CONCLUSION Our study shows a significantly higher rate of adenomas in HCV patients compared to the general population.Prospective studies would help determine if the increase in adenoma detection lowers the risk for colorectal cancer.展开更多
Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,the sixth most common cancer worldwide,and the third leading cause of cancer-related death.Cirrhosis is the predominant risk factor for HCC,...Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,the sixth most common cancer worldwide,and the third leading cause of cancer-related death.Cirrhosis is the predominant risk factor for HCC,driven by major etiologies including hepatitis B and C,excessive alcohol consumption,and metabolic dysfunction-associated steatotic liver disease(MASLD).While approximately 80%of HCC cases occur in patients with cirrhosis,its incidence among individuals without cirrhosis has significantly increased,particularly in developed countries,driven by the rising prevalence of MASLD.The prevalence of patients with non-cirrhotic HCC varies geographically,yet data on this subgroup remain limited.Consequently,screening and clinical management guidelines for patients with non-cirrhotic HCC are underdeveloped.Current surveillance is typically not recommended for non-cirrhotic populations,except for individuals with hepatitis B,and diagnostic criteria like Liver Imaging Reporting and Data System are designed explicitly for cirrhotic or hepatitis B-associated HCC.Furthermore,treatment strategies for non-cirrhotic HCC are often extrapolated from studies focused on patients with cirrhosis,leading to gaps in knowledge regarding treatment efficacy,survival outcomes,and etiological variability in noncirrhotic cohorts.Thus,emerging evidence must be reviewed to guide the development of enhanced diagnostic and therapeutic strategies for patients with non-cirrhotic HCC.To address these gaps,we comprehensively reviewed the epidemiology,clinical and genetic characteristics,diagnostic modalities,and therapeutic approaches for patients with non-cirrhotic HCC.展开更多
BACKGROUND Liver cancer poses a significant public health threat.The difference between disease patterns and national policies is crucial to elucidating factors influencing hepatocellular carcinoma(HCC)incidence.AIM T...BACKGROUND Liver cancer poses a significant public health threat.The difference between disease patterns and national policies is crucial to elucidating factors influencing hepatocellular carcinoma(HCC)incidence.AIM To investigate the secular trend and disease pattern of liver cancer in Taiwan Region of China,Poland,and Belgium.METHODS This population-based cohort study presents the incidence,period,and cohort effects in HCC incidence between 2000 and 2019 in Taiwan Region of China,Poland,and Flanders,Belgium.Data on HCC were obtained from cancer registry data from Taiwan Region of China,Poland,and regional data from Belgium.Age-standardized incidence rates(ASIRs),annual per-centage changes,and age-period-cohort analyses were conducted by sex and period.RESULTS Taiwan’s Region of China ASIR decreased from 2000 to 2019(males:55.17 to 43.42,females:21.91 to 16.20,per 100000).In Poland,ASIR declined from 2000 to 2019(males:3.21 to 2.77,females:1.95 to 1.32,per 100000).However,Flanders experienced an increase in ASIR from 2000 to 2019(males:2.66 to 5.63,females:1.40 to 2.20,per 100000).In Taiwan Region of China,the cohort effect rate ratio increased from 1915 to 1935(males:1.02 to 1.36,females:1.04 to 1.54)and decreased from 1935 to 1989(males:1.36 to 0.22,females:1.54 to 0.20).In Poland,rate ratios consistently decreased(males:1.75 to 0.25,females:3.46 to 0.26).Flanders exhibited an increase in both males(0.14 to 2.52,1915 to 1975)and females(0.53 to 3.66,1915 to 1989).CONCLUSION Taiwan Region of China and Poland’s declining ASIR may be due to effective hepatitis B virus immunization and viral hepatitis therapy.Flanders’persistent increase may be tied to higher HCC risk in high hepatitis C virus risk populations.展开更多
BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepat...BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.展开更多
文摘BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of direct-acting antiviral(DAA)treatment in HCV-infected patients.METHODS The study included consecutive 9457 women and 9529 men,treated with DAA for chronic HCV infection from July 2015 to the end of 2023 whose data were collected in the nationwide multicenter retrospective Epiter-2 project.Women were divided into pre-menopausal(15-44 years),menopausal(45-55 years)and post-menopausal(>55 years)and compared with age-matched men.RESULTS Regardless of age,women had a significantly lower body mass index,prevalence of genotype 3 infection and proportion of cirrhosis compared to men.Psychiatric disorders(except depression),hepatitis B virus and human immunodeficiency virus co-infections,as well as alcohol and drug addiction,were significantly less common in women than in men in all age groups.The sustained virologic response was significantly higher in women compared to men in each age group and amounted to 98.4%and 96.6%,respectively(P<0.001).Independent predictors of treatment failure in women were genotype 3 infection,cirrhosis and postmenopausal age.Mild adverse events were reported significantly more often by women,regardless of age with the highest percentage in the postmenopausal group.CONCLUSION DAA treatment is more effective in women than in men,regardless of age,but in postmenopausal women,the effectiveness is relatively the lowest.
文摘The aim of this study was to assess the seroprevalence of viral hepatitis B and C and co-infection with HIV among volunteer blood donors at the blood sampling and distribution depot (BSDD) in Ouahigouya. Patients and methods: Our study population consisted of all volunteer blood donors who had donated during a 2-year period from 1 January 2019 to 31 December 2020. Samples were taken from patients with no contraindications and serological tests were performed using ELISA tests. HBsAg, HCV-Ac and HIV serology were tested. All samples reactive for HIV, HBV and HCV were retested for confirmation using a second enzyme-linked immunosorbent assay. A result was considered positive if both the first and second tests were positive. Results: In two years, the Ouahigouya BSDD recorded 9726 donations, including 7983 new donors and 1743 former donors. The average age of donors was 25.59 years, with a sex ratio of 3.4. The seroprevalence of HBV, HCV and HIV was 7.31%, 3.10% and 2.12% respectively. HBV-HCV co-infection was found in 0.32% of cases, HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infection were found in 0.25%, 0.09% and 0.04% respectively. Conclusion: The seroprevalence of viral hepatitis B and C remains high among volunteer blood donors in Ouahigouya, although a decline in seroprevalence appears to be on the horizon.
基金supported by a grant from the R&D Program of China(2022YFC2304500).
文摘To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.
文摘Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.
基金The National Key Research and Development Program(2022YFC2603500,2022YFC2603505,2023YFC2306901,2023YFC2308105)The capital health research and development of special public health project(2022-1-2172)+3 种基金Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26Beijing Hospitals Authority“peak”talent training program(DFL20241803)Beijing Hospitals Authority Clinical medicine Development of special funding support(ZLRK202301)Beijing Research Ward Excellence Program(BRWEP2024W102170101)。
文摘Objective To investigate chronic hepatitis C virus(HCV)infection's effect on gestational liver function,pregnancy and delivery complications,and neonatal development.Methods A total of 157 HCV antibody-positive(anti-HCV[+])and HCV RNA(+)patients(Group C)and121 anti-HCV(+)and HCV RNA(-)patients(Group B)were included as study participants,while 142 antiHCV(-)and HCV RNA(-)patients(Group A)were the control group.Data on biochemical indices during pregnancy,pregnancy complications,delivery-related information,and neonatal complications were also collected.Results Elevated alanine aminotransferase(ALT)rates in Group C during early,middle,and late pregnancy were 59.87%,43.95%,and 42.04%,respectively—significantly higher than Groups B(26.45%,15.70%,10.74%)and A(23.94%,19.01%,6.34%)(P<0.05).Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages(P<0.05).No significant differences were found in neonatal malformation rates across groups(P>0.05).However,neonatal jaundice incidence was significantly greater in Group C(75.16%)compared to Groups A(42.25%)and B(57.02%)(χ^(2)=33.552,P<0.001).HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice(OR=2.111,95%CI 1.242–3.588,P=0.006).Conclusions Chronic HCV infection can affect the liver function of pregnant women,but does not increase the pregnancy or delivery complication risks.HCV RNA(+)is an independent risk factor for neonatal jaundice.
文摘BACKGROUND Liver imaging and transient elastography(TE)are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus(HCV)infection.However,the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.AIM To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.METHODS We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019.We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging.Liver imaging findings(hepatic steatosis,increased echogenicity,cirrhosis,and chronic liver disease)were further evaluated for their diagnostic performance in detecting fibrosis(≥F2,≥F3,≥F4)and steatosis(≥S1,≥S2,≥S3).RESULTS Of 959 HCV patients who underwent TE,651 had liver imaging.Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings(P=0.0050),hepatic steatosis(P<0.0001),and increased echogenicity(P<0.0001).Higher liver stiffness measurement values were also noted in those with abnormal liver(P<0.0001)and increased echogenicity(P=0.0026).Steatosis severity correlated with hepatic steatosis(r=0.195,P<0.001)and increased echogenicity(r=0.209,P<0.001).For fibrosis detection,abnormal liver imaging had moderate sensitivity(81.7%)and specificity(70.4%)for cirrhosis(≥F4),while cirrhosis on imaging had high specificity(99.2%)but low sensitivity(18.3%).Increased echogenicity showed high specificity(92.8%)but low sensitivity(20.9%)for steatosis detection.CONCLUSION Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity.Integrating TE with imaging may improve evaluation in patients with HCV.
文摘BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist for diagnosing chronic HCV infection.Though beneficial,invasive procedures can cause morbidity and inadequate representation of the overall degree of fibrosis.Due to these reasons,non-invasive liver fibrosis biomarkers are becoming more prevalent to diagnose and track liver fibrosis without a liver biopsy.These biomarkers can detect liver fibrosis early,improving treatment and preventing cirrhosis and liver failure.Micro ribonucleic acid(MiRNA)dysregulation causes and worsens several diseases including liver disease.MiRNAs can facilitate the diagnosis of liver fibrosis and serve as a predictive tool to enhance patient care by minimizing invasive procedures and enabling more efficient and prompt therapy.AIM To investigate the diagnostic effectiveness of several miRNAs(miRNA-122,miRNA-21,miRNA-199a,miRNA-155)in assessing the liver fibrosis severity in untreated HCV patients from the Indian Punjab population.We seek to identify the intricate diagnostic relationship of miRNAs with the extent of fibrosis among individuals with HCV.METHODS We considered 100 persons determined as HCV infected by a quantitative Real-Time Polymerase Chain Reaction examination.We employed statistical as well as probabilistic tools to ascertain the diagnostic validity of miRNAs for determining the liver fibrosis stages.We employed Bayesian Networks,to introduce a unique diagnostic paradigm for miRNAs that can be adopted as benchmark to evaluate the liver fibrosis severity in HCV cases.RESULTS We found that miRNAs(miR-122,miR-155 and miR-21)showed significant upregulation when compared with control and according to severity of fibrosis(P≤0.05).The area under the curve for miR-122,miR-155,miR-21 and miR-199a in HCV group in relation to Liver Stiffness Measurement was calculated as 0.889,0.933,0.912 and 0.035 respectively.MiR-199a was downregulated according to degree of fibrosis.CONCLUSION Depending on the diagnostic accuracy,we have concluded that miR-122,miR-155 and miR-21 are reliable markers to detect fibrosis in Hepatitis C patients.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research Grant.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
文摘AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.
文摘BACKGROUND Hepatitis B virus(HBV)infection is a major factor responsible for HBV+hepatocellular carcinoma(HCC).AIM An immunological classification of HBV+HCC may provide both biological insights and clinical implications for this disease.METHODS Based on the enrichment of 23 immune signatures,we identified two immunespecific subtypes(Imm-H and Imm-L)of HBV+HCC by unsupervised clustering.We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.RESULTS Compared to Imm-L,Imm-H displayed stronger immunity,more stromal components,lower tumor purity,lower stemness and intratumor heterogeneity,lower-level copy number alterations,higher global methylation level,and better overall and disease-free survival prognosis.Besides immune-related pathways,stromal pathways(ECM receptor interaction,focal adhesion,and regulation of actin cytoskeleton)and neuro-related pathways(neuroactive ligand-receptor interaction,and prion diseases)were more highly enriched in Imm-H than in Imm-L.We identified nine proteins differentially expressed between Imm-H and Imm-L,of which MYH11,PDCD4,Dvl3,and Syk were upregulated in Imm-H,while PCNA,Acetyl-a-Tubulin-Lys40,ER-α_pS118,Cyclin E2,andβ-Catenin were upregulated in Imm-L.CONCLUSION Our data suggest that“hot”tumors have a better prognosis than“cold”tumors in HBV+HCC and that“hot”tumors respond better to immunotherapy.
基金Supported by the JSPS Kakenhi Grant,No.JP24K15491.
文摘Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.
文摘Delving into the immunological crossroads of liver diseases,this editorial explores the dynamic interplay between hepatitis C virus(HCV)and autoimmune hepatitis(AIH).While HCV primarily manifests as a viral infection impacting the liver,previous studies unveil a captivating connection between HCV and the emergence of AIH.The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH.Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection,hinting at a potential overlap between viral and autoimmune liver diseases.Navigating the intricate terrain of viral replication,immune response dynamics,and genetic predisposition,this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH.In this immunological crossroads,we aim to unearth insights into the complex interplay,using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.
基金Supported by the Clinical Research Fellowship Grant from the Wellcome Trust,United Kingdom,No.227516/Z/23/Z.
文摘BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.CONCLUSION Although,studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease,HCC,and liver-related death,there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3.Only cirrhosis and age have demonstrated an association;however,the number of studies is very small,and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
基金supported by the Dengfeng Talent Support Program of Beijing Municipal Administration of Hospitals[Grant No.DFL20221601]the Natural Science Foundation of Beijing[Grant No.7212053]Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[Grant No.ZYYCXTD-C-202006].
文摘Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.
文摘BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.
文摘BACKGROUND Chronic hepatitis C virus(HCV)has been associated with hepatic and extrahe-patic malignancies.Limited studies have shown an association between colorectal adenomas and HCV populations.AIM To study the prevalence of colorectal adenomas in patients with HCV compared to the general population and to evaluate if it is an independent risk factor for colorectal adenomas.METHODS Patients were divided into HCV and non-HCV based on their HCV RNA titers.Patients with alcoholic liver disease,hepatitis B infection,and inflammatory bowel disease were excluded.Continuous variables were analyzed using the Mann-Whitney U test,and categorical variables usingχ^(2) with P<0.05 were considered statistically significant.The significant covariates(independent variables)were matched in both groups by propensity score matching,followed by multivariate regression analysis.RESULTS Of the 415 patients screened,109 HCV patients and 97 non-HCV patients with colonoscopy results were included in the study.HCV patients were older,had a smoking history,had less frequent aspirin use,and had a lower body mass index(BMI)(P<0.05).The HCV cohort had a significantly increased number of patients with adenomas(adenoma detection rate of 53.2%vs 34%.P=0.006).We performed a propensity-matched multivariate analysis where HCV infection was significantly associated with colorectal adenoma(OR:2.070,P=0.019).CONCLUSION Our study shows a significantly higher rate of adenomas in HCV patients compared to the general population.Prospective studies would help determine if the increase in adenoma detection lowers the risk for colorectal cancer.
文摘Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,the sixth most common cancer worldwide,and the third leading cause of cancer-related death.Cirrhosis is the predominant risk factor for HCC,driven by major etiologies including hepatitis B and C,excessive alcohol consumption,and metabolic dysfunction-associated steatotic liver disease(MASLD).While approximately 80%of HCC cases occur in patients with cirrhosis,its incidence among individuals without cirrhosis has significantly increased,particularly in developed countries,driven by the rising prevalence of MASLD.The prevalence of patients with non-cirrhotic HCC varies geographically,yet data on this subgroup remain limited.Consequently,screening and clinical management guidelines for patients with non-cirrhotic HCC are underdeveloped.Current surveillance is typically not recommended for non-cirrhotic populations,except for individuals with hepatitis B,and diagnostic criteria like Liver Imaging Reporting and Data System are designed explicitly for cirrhotic or hepatitis B-associated HCC.Furthermore,treatment strategies for non-cirrhotic HCC are often extrapolated from studies focused on patients with cirrhosis,leading to gaps in knowledge regarding treatment efficacy,survival outcomes,and etiological variability in noncirrhotic cohorts.Thus,emerging evidence must be reviewed to guide the development of enhanced diagnostic and therapeutic strategies for patients with non-cirrhotic HCC.To address these gaps,we comprehensively reviewed the epidemiology,clinical and genetic characteristics,diagnostic modalities,and therapeutic approaches for patients with non-cirrhotic HCC.
文摘BACKGROUND Liver cancer poses a significant public health threat.The difference between disease patterns and national policies is crucial to elucidating factors influencing hepatocellular carcinoma(HCC)incidence.AIM To investigate the secular trend and disease pattern of liver cancer in Taiwan Region of China,Poland,and Belgium.METHODS This population-based cohort study presents the incidence,period,and cohort effects in HCC incidence between 2000 and 2019 in Taiwan Region of China,Poland,and Flanders,Belgium.Data on HCC were obtained from cancer registry data from Taiwan Region of China,Poland,and regional data from Belgium.Age-standardized incidence rates(ASIRs),annual per-centage changes,and age-period-cohort analyses were conducted by sex and period.RESULTS Taiwan’s Region of China ASIR decreased from 2000 to 2019(males:55.17 to 43.42,females:21.91 to 16.20,per 100000).In Poland,ASIR declined from 2000 to 2019(males:3.21 to 2.77,females:1.95 to 1.32,per 100000).However,Flanders experienced an increase in ASIR from 2000 to 2019(males:2.66 to 5.63,females:1.40 to 2.20,per 100000).In Taiwan Region of China,the cohort effect rate ratio increased from 1915 to 1935(males:1.02 to 1.36,females:1.04 to 1.54)and decreased from 1935 to 1989(males:1.36 to 0.22,females:1.54 to 0.20).In Poland,rate ratios consistently decreased(males:1.75 to 0.25,females:3.46 to 0.26).Flanders exhibited an increase in both males(0.14 to 2.52,1915 to 1975)and females(0.53 to 3.66,1915 to 1989).CONCLUSION Taiwan Region of China and Poland’s declining ASIR may be due to effective hepatitis B virus immunization and viral hepatitis therapy.Flanders’persistent increase may be tied to higher HCC risk in high hepatitis C virus risk populations.
文摘BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.
