Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

Chronic Hepatitis B in Indian Americans: Lack of Screening and Poor Linkage to Care

Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.

Factors Associated with Renal Impairment in Patients on Tenofovir for Chronic Hepatitis B in Yaoundé (Cameroon)

Background: Tenofovir (TFV) is widely used to treat patients with hepatitis B virus (HBV) infection. But kidney abnormalities are the main concern using this drug. Few studies have described the renal impairment due to the TFV in chronic hepatitis B (CHB) in Sub-Saharan Africa. The objective was to evaluate factors associated with renal impairment observed in patients on TFV for CHB. Method: It was a hospital based cross sectional prospective study carried out from June 2023 to July 2023 in Yaoundé (Cameroon) and included any patient treated with TFV for CHB during at least a period of 6 months. For each participant, we collected in the medical report socio-demographic data, clinical data, baseline creatinine, treatment information (type of TFV which was Disoproxil Fumarate (TDF) or Alafenamide (TAF), duration). Then, we collected blood samples to measure serum creatinine and phosphate levels and urine dipstick analysis. Factors associated with renal impairment were assessed with the Odds Ratio. A p value of Results: A total of 60 participants were included. The median age was 44 years [36-55] and median duration of TFV therapy was 17.5 months [11.7-25.7]. The prevalence of reduced eGFR (Conclusion: Kidney function was impaired in some patients receiving TFV for CHB. It should be monitored, particularly after 36 months and for those receiving TDF prodrug.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Chronic hepatitis B:Prevent,diagnose,and treat before the point of no return

Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.

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.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Chronic hepatitis B virus infection in Eastern Ethiopia:Clinical characteristics and determinants of cirrhosis

BACKGROUND Chronic hepatitis B(CHB)virus infection is a major cause of liver-associated morbidity and mortality,particularly in low-income countries.A better understanding of the epidemiological,clinical,and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia.AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment.METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019.Baseline assessments included chemistry,serologic,and viral markers.χ^(2) tests,Mann-Whitney U tests,and logistic regression analyses were used to identify the determinants of cirrhosis.Tenofovir disoproxil fumarate(TDF)was initiated using treatment criteria from the Ethiopian CHB pilot program.RESULTS A total of 132 patients(68.4%)were men,with a median age of 30 years[interquartile range(IQR):24-38].At enrollment,60(31.1%)patients had cirrhosis,of whom 35(58.3%)had decompensated cirrhosis.Khat use,hepatitis B envelope antigen positivity,and a high viral load were independently associated with cirrhosis.Additionally,66 patients(33.4%)fulfilled the treatment criteria and 59(30.6%)started TDF.Among 29 patients who completed 24 months of treatment,the median aspartate aminotransferase to platelet ratio index declined from 1.54(IQR:0.66-2.91)to 1.10(IQR:0.75-2.53)(P=0.002),and viral suppression was achieved in 80.9%and 100%of patients after 12 months and 24 months of treatment,respectively.Among the treated patients,12(20.3%)died within the first 6 months of treatment,of whom 8 had decompensated cirrhosis.CONCLUSION This study highlights the high prevalence of cirrhosis,initial mortality,and the efficacy of TDF treatment.Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与CHB肝纤维化严重程度的相关性及对疾病预后的预测价值

目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预后的预测价值。方法选取河南省中医院2021年3月至2022年3月收治的78例CHB肝纤维化患者作为研究组,选择同期78名健康体检者作为对照组。比较研究组和对照组及不同肝纤维化分期、不同炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平与肝纤维化分期、炎症活动分级的相关性。CHB肝纤维化患者治疗3个月后,根据患者预后分为预后良好和预后不良亚组,比较预后良好和预后不良患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平联合检测对CHB肝纤维化患者预后不良的预测价值。结果研究组入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ高于对照组(P<0.05);不同肝纤维化分期、炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ比较:S1<S2<S3<S4、G1<G2<G3<G4,差异有统计学意义(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与肝纤维化分期、炎症活动分级均呈正相关(P<0.05)。预后良好患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平均低于预后不良患者(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平联合预测肝纤维化患者预后不良的曲线下面积(AUC)优于各指标单一检测(P<0.05)。结论CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平均呈现高表达,且与肝纤维化分期、炎症活动分级密切相关,其联合检测对CHB肝纤维化患者预后有较高的预测价值,可用于评估CHB肝纤维化患者病情严重程度和预后,为制定针对性治疗措施提供参考。

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients

BACKGROUND The clinical and histological features of chronic hepatitis B(CHB)patients who fall into the"grey zone(GZ)"and do not fit into conventional natural phases are unclear.AIM To explore the impact of varying the threshold of alanine aminotransferase(ALT)levels in identifying significant liver injury among GZ patients.METHODS This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy.The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines.GZ CHB patients were classified into four groups:GZ-A(HBeAg positive,normal ALT levels,and HBV DNA≤10^(7) IU/mL),GZ-B(HBeAg positive,elevated ALT levels,and HBV DNA<10^(4) or>10^(7) IU/mL),GZC(HBeAg negative,normal ALT levels,and HBV DNA≥2000 IU/mL),and GZ-D(HBeAg negative,elevated ALT levels,and HBV DNA≤2000 IU/mL).Significant hepatic injury(SHI)was defined as the presence of notable liver inflammation(≥G2)and/or significant fibrosis(≥S2).RESULTS The results showed that 50.22%of patients were classified as GZ,and 63.7%of GZ patients developed SHI.The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria(35 U/L for men and 25 U/L for women)can more accurately identify patients with significant liver damage in the GZ phases.In total,the proportion of patients with ALT≤40 U/L who required antiviral therapy was 64.86%[(221+294)/794].When we lowered the ALT treatment threshold to the new criteria(30 U/L for men and 19 U/L for women),the same outcome was revealed,and the proportion of patients with ALT≤40 U/L who required antiviral therapy was 75.44%[(401+198)/794].Additionally,the proportion of SHI was 49.1%in patients under 30 years old and increased to 55.3%in patients over 30 years old(P=0.136).CONCLUSION These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Clinicopathological features of 11 cases of chronic hepatitis B infection complicated with primary biliary cholangitis

BACKGROUND Only a few cases of chronic hepatitis B(CHB)with primary biliary cholangitis(PBC)have been reported based on histological evidence from liver biopsies.AIM To observe the clinicopathological features and outcomes of 11 patients with CHB infection complicated by PBC.METHODS Eleven patients with CHB and PBC who underwent liver biopsy at the Zhenjiang Third Hospital,affiliated with Jiangsu University,and Wuxi Fifth People’s Hospital,from January 2005 to September 2020,were selected.All patients initially visited our hospital with CHB and were pathologically diagnosed with CHB and PBC.RESULTS Only five had elevated alkaline phosphatase levels,nine were positive for antimitochondrial antibody(AMA)-M2,and two were negative for AMA-M2.Two had jaundice and pruritus symptoms,10 had mildly abnormal liver function,and one had severely elevated bilirubin and liver enzyme levels.The pathological characteristics of CHB complicated by PBC overlapped with those of PBCautoimmune hepatitis(AIH).When necroinflammation of the portal area is not obvious,the pathological features of PBC are predominant,similar to the features of PBC alone.When the interface is severe,biliangitis will occur,with a large number of ductular reactions in zone 3.Unlike the PBC-AIH overlap pathology,this pathology is characterized by a small amount of plasma cell infiltration.Unlike PBC,lobulitis is often observed.CONCLUSION This is the first large case series to show that the rare pathological features of CHB with PBC are similar to those of PBC-AIH and small duct injury was observed.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B

BACKGROUND Research exploring the influence of healthier lifestyle modification(LSM)on the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB)is limited.AIM To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data.METHODS Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1,2009,and December 31,2017,those aged≥20 years who drank alcohol,smoked cigarettes,and were sedentary were analyzed.Exposure included at least one LSM,including alcohol abstinence,smoking cessation,and regular exercise.The primary outcome was HCC development,and the secondary outcome was liver-related mortality.We used 2:1 propensity score matching to account for covariates.RESULTS With 48766 patients in the LSM group and 103560 in the control group,the adjusted hazard ratio(HR)for incident HCC and liver-related mortality was 0.92[95%confidence interval(CI):0.87-0.96]and 0.92(95%CI:0.86-0.99)in the LSM group,respectively,compared with the control group.Among the LSM group,the adjusted HR(95%CI)for incident HCC was 0.84(0.76-0.94),0.87(0.81-0.94),and 1.08(1.00-1.16)for alcohol abstinence,smoking cessation,and regular exercise,respectively.The adjusted HR(95%CI)for liver-related mortality was 0.92(0.80-1.06),0.81(0.72-0.91),and 1.15(1.04-1.27)for alcohol abstinence,smoking cessation,and regular exercise,respectively.CONCLUSION LSM lowered the risk of HCC and mortality in patients with CHB.Thus,active LSM,particularly alcohol abstinence and smoking cessation,should be encouraged in patients with CHB.

Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis

BACKGROUND Type 2 diabetes mellitus(T2DM)has been shown to be correlated with hepatocellular carcinoma(HCC)development.However,further investigation is needed to understand how T2DM characteristics affect the prognosis of chronic hepatitis B(CHB)patients.AIM To assess the effect of T2DM on CHB patients with cirrhosis and to determine the risk factors for HCC development.METHODS Among the 412 CHB patients with cirrhosis enrolled in this study,there were 196with T2DM.The patients in the T2DM group were compared to the remaining 216patients without T2DM(non-T2DM group).Clinical characteristics and outcomes of the two groups were reviewed and compared.RESULTS T2DM was significantly related to hepatocarcinogenesis in this study(P=0.002).The presence of T2DM,being male,alcohol abuse status,alpha-fetoprotein>20ng/mL,and hepatitis B surface antigen>2.0 log IU/mL were identified to be risk factors for HCC development in the multivariate analysis.T2DM duration of more than 5 years and treatment with diet control or insulin±sulfonylurea significantly increased the risk of hepatocarcinogenesis.CONCLUSION T2DM and its characteristics increase the risk of HCC in CHB patients with cirrhosis.The importance of diabetic control should be emphasized for these patients.

Relationship between the Polymorphism of the GSTP1 (rs1695) Gene and Chronic Hepatitis B Infection in Ouagadougou, Burkina Faso

Introduction: Genetic polymorphisms of some Glutathione S-Transferase (GST) which encode the enzyme responsible for the biotransformation of drugs and xenobiotics, have been associated with the risk of several pathologies that can progress to cancer such as Hepatitis B. This study aims to characterize the impact of the rs1695 polymorphism of GSTP1 gene among people with chronic Hepatitis B infection in Burkina Faso. Methods: rs1695 polymorphisms of GSTP1 gene genotyping was performed for 50 people infected with chronic Hepatitis B virus and 124 healthy people with the PCR-RFLP method. Conventional PCR was used for DNA amplification and Alw26I enzyme was used for enzymatic digestion. Results: The results show that the frequencies of AA, AG and GG genotypes are respectively 31.00%, 36.80% and 32.20% in general the study population with a mutation rate of 50.57%. However, the incidence of the AA, AG and GG genotypes are respectively 30.64%, 38.71% and 30.64% among people with chronic Hepatitis B virus infection and 32.00%, 32.00% and 36.00% among healthy people. In cases, the frequencies of the A and G alleles are 48.00% and 52.00% respectively, and in controls 50.00% each. No statistical difference was found by comparing genotypic and allelic frequencies between cases and controls (p > 0.05). Conclusion: Our study allowed us to determine the rate of GSTP1 rs1695 genotypes in the study population, cases and controls. From our analyses, GSTP1 rs1695 is not associated to chronic Hepatitis B virus infection in Ouagadougou.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir

BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Evaluation of Non-Invasive Markers of Liver Fibrosis in Chronic Hepatitis B Patients in a Sub-Saharan African Setting: Transient Elastography versus APRI, FIB4, GTT/Platelet Scores

Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.