Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a responseguided therapy strategy

BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

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.

Hepatitis B Surface Antigen and Hepatitis C Virus Antibodies among Drug Users in Burkina Faso

Introduction: The epidemiology of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among drug users (DUs) is little known in West Africa. The study aimed to assess the prevalence of hepatitis B and C viruses among drug users in Burkina Faso. Methodology: This was a cross-sectional biological and behavioral survey conducted between June and August 2022, among drug users in Ouagadougou and Bobo Dioulasso, the two main cities of Burkina Faso. A respondent-driven sampling (RDS) was used to recruit drug users. Hepatitis B surface antigen was determined using lateral flow rapid test kits and antibodies to hepatitis C virus in serum determined using an Enzyme-Linked Immunosorbent Assay. Data were entered and analyzed using Stata 17 software. Weighted binary logistic regression was used to identify the associated factors of hepatitis B and C infections and a p-value Results: A total of 323 drug users were recruited with 97.5% males. The mean age was 32.7 years old. The inhaled or smoked mode was the most used by drug users. The adjusted hepatitis B and hepatitis C prevalence among study participants were 11.1% and 2.3% respectively. The marital status (p = 0.001), and the nationality (p = 0.011) were significantly associated with hepatitis B infection. The type of drug used was not significantly associated with hepatitis B infection or hepatitis C infection. Conclusion: The prevalence of HBsAg and anti-HCV antibodies among DUs are comparable to those reported in the general population in Burkina Faso. This result suggests that the main routes of contamination by HBV and HCV among DUs are similar to those in the population, and could be explained by the low use of the injectable route by DUs in Burkina Faso.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

State of the HIV, Hepatitis B and C Virus Pandemic from 2003 to 2022 in Burkina Faso: Evolution of Prevalence Trends and Strategic Recommendations to Achieve the WHO’s Goal for Their Eradication by 2030

Background: The World Health Organization (WHO) has set a goal to eradicate or at least significantly reduce the prevalence the human immunodeficiency virus (HIV), hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) by 2030. The main objective was to provide an evolving overview of the prevalence of HIV, HBV and HCV infection between 2003 and 2022 in Burkina Faso. Methods: It was a retrospective cross-sectional study based on data from 2003 to 2022. The data were collected using information available in the databases of the HOSCO and CERBA laboratories and included all individuals who underwent HIV and/or HBV and/or HCV testing. Data analysis was performed using SPSS version 20.0, EpiInfo 7, and R version 4.1.0. Results were considered statistically significant if p Results: The study recorded 7432 samples and the mean age of the subjects was 27.98 ± 8.50 years. During this period, the respective prevalence of HIV, HBV, and HCV were 4.66% (346/7432), 8.77% (582/6636) and 5.54% (322/5816). However, from 2003 to 2022, there was a significant decrease (P y=−1.75x+12.59;y=−0.24x+10.01and y=−0.11x+6.02, with “y” corresponding to prevalence and “x” to the years. Conclusion: Burkina Faso needs to rigorously apply prevention and control strategies recommended by the WHO by 2030.

Current research status of transarterial therapies for hepatocellular carcinoma

With continuous advancements in interventional radiology,considerable progress has been made in transarterial therapies for hepatocellular carcinoma(HCC)in recent years,and an increasing number of research papers on transarterial therapies for HCC have been published.In this editorial,we comment on the article by Ma et al published in the recent issue of the World Journal of Gastrointestinal Oncology:“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”.We focus specifically on the current research status and future directions of transarterial therapies.In the future,more studies are needed to determine the optimal transarterial local treatment for HCC.With the emergence of checkpoint immunotherapy modalities,it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

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.

Analysis of articles on hepatitis C by scientific mapping:1989-2022

BACKGROUND Hepatitis C virus(HCV)poses a significant quandary about public health.It is challenging to study the literature in a particular discipline comprehensively today.One solution is bibliometric analysis,which is often used to track the attributes and evolutionary trajectories of scientific outputs.AIM To examine the 35-year scientific evolution of articles focused on HCV.METHODS This study examined the 35-year scientific evolution of articles focused on HCV.Our study utilized the Web of Science database.The study encompassed a total of 11930 articles.RESULTS Regarding the cumulative count of articles,the leading countries are the United States,Japan,and Italy.Rice CM is the author with the highest recorded H-index and G-index values.The journal with the highest recorded H-index and G-index values is the Journal of Virology.The Journal of Viral Hepatitis contributed 10.94%of the articles,whereas the Journal of Virology published 9.68%.According to the strategic diagram,the keywords most frequently used in 2020-2022 are HCV,epidemiology,and sofosbuvir.CONCLUSION This study provides valuable information about 40 years of academic knowledge on HCV.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

Despite achieving a high cure rate with the direct-acting antivirals(DAAs)in hepatitis C treatment,further research is needed to identify additional benefits of the DAA therapy.The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs,who also achieved sustained virologic response.By the fibrosis-4(FIB-4)index,patients were categorized based on their baseline fibrosis levels,and the improvement in fibrosis was analyzed in both short-term(9-26 weeks)and long-term(≥36 weeks)follow-up.The results showed a significant decrease in the FIB-4 index,indicating an improvement in liver fibrosis,in 63.0%and 67.6%of the patients during the short-term and long-term follow-up,respectively.Short-term improvement was associated with factors including ribavirin usage,blood cholinesterase levels,alanine transaminase levels,albumin levels,and the baseline FIB-4 index,while long-term improvement was associated with factors such as aspartate transaminase levels,total protein level,and the baseline FIB-4 index.The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis,which will provide crucial insights for enhancing patient care in hepatitis C management.

Immunological crossroads:The intriguing dance between hepatitis C and autoimmune hepatitis

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.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection:A systematic review

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.

Liver biopsy in the post-hepatitis C virus era in Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

New markers of fibrosis in hepatitis C:A step towards the Holy Grail?

In the present issue of the World Journal of Hepatology,Ferrassi et al examine the problem of liver fibrosis staging in chronic hepatitis C.They identify novel biomarkers in an effort to predict accurate fibrosis staging with the aid of the metabolome of Hepatitis C patients.Overall I think Ferrassi et al took a different approach in identifying fibrosis biomarkers,by looking at the patients’metabolome.Their biomarkers clearly separate patients from controls.They can also separate out,patients with minimal fibrosis(F0-F1 stage)and patients with cirrhosis(F4 stage).Obviously,if these biomarkers were to be widely used,tests for all the important metabolites would need to be readily available for use in hospitals or outpatient setting and that may prove difficult and above all,costly.Nevertheless,this step could eventually lead to a metabolomic approach for novel biomarkers of Fibrosis.Obviously,it would need to be validated,but could represent a step towards the Holy Grail of Hepatology.

Advances in Conversion Therapy for Primary Unresectable Hepatocellular Carcinoma

Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.