Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment

Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

Liver-related effects of chronic hepatitis C antiviral treatment

More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic hepatitis C(CHC),including patients with cirrhosis.The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis,but the exact cause of the expected benefit was unclear.Further,little was known about how the underlying liver disease would be affected during and after viral clearance.In this review,we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activation,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liver changes,and liver function,as these factors are all related to morbidity and mortality in CHC patients.It seems clear that antiviral therapy,especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis.There seems to be a timedependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions.These improvements lead to favorable effects on liver function,followed by an improvement in cognitive dysfunction and portal hypertension.Overall,the data provide knowledge on the several beneficial effects of DAA therapy on liverrelated parameters in CHC patients suggesting short-and long-term improvements in the underlying disease with the promise of an improved longterm prognosis.

Tumor characteristics of hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C: Comparative analysis with antiviral therapy-naive patients

BACKGROUND Insufficient and contradictory data are available about the relation between directacting antivirals(DAAs)and hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV).AIM To analyze differences in basic clinical,radiological,and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure.METHODS This multicenter case-control study included 497 patients with chronic HCVrelated HCC,allocated into one of two groups according to their history of antiviral treatment for their HCV.RESULTS Group I included 151 HCC patients with a history of DAAs,while 346 patients who had never been treated with DAAs were assigned to group II.A significant difference was observed between both groups regarding basic assessment scores(Child,MELD,and BCLC),which tended to have more advanced liver disease and HCC stage upon diagnosis in group I.However,serum albumin was significantly affected,and serumα-fetoprotein was significantly higher in group II(P<0.001).In addition,group I showed significant HCC multicentricity than group II,while the incidence of portal vein thrombosis was significantly higher in group I(P<0.001).CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment;however,HCC behavior is more aggressive in DAA-treated patients.

Traditional Chinese medicine in antiviral treatment

The Novel Coronavirus(COVID-19),which broke out in Wuhan,China in December 2019,attracted worldwide attention.With a long incubation period and strong infectiousness,COVID-19 poses a great threat to the life and health worldwide with high incidence,high pathogenicity and low sensitivity to antibiotics.At present,there are less kinds of antiviral drugs,including rimantadine hydiochloride,acyclovir,interferon,zidovudine,ribavirin,etc.,which maybe lead to severe adverse reactions of the nervous system,hematopoietic system,liver and kidney system,as well as side effects such as nausea,vomiting,upper abdominal discomfort and diarrhea.Meanwhile,the development of antiviral drugs requires huge investment and time,the development of effective antiviral drugs and vaccine lags far behind the rapidly developed disease.Traditional Chinese medicine has played an important role against the infection,especially in the fight against severe acute respiratory syndrome,H1N1 influenza,H7N9 flu virus,middle east respiratory syndrome and Ebola virus infection.In this paper,the classification,mechanism,existing problems and the prospect of traditional Chinese medicine in antiviral treatment has been summarized in order to provide certain reference for the research and prescription screening of traditional Chinese medicine anti-COVID-19 drugs.

Chinese Consensus on Antiviral Treatment of Chronic Hepatits B Patients with Nucleos(t)ide Analogues

Antiviral treatment is the main method for chronic hepatitis B(CHB).After antiviral treatment,some patients may obtain satisfactory therapeutic effect,but some patients still show primary non-response,suboptimal response,even resistance to nucleos(t)ide analogues or relapse,which are becoming the key problems and confusing the clinical staffs.Thus,in January 2013,editorial department of Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition),Chinese Journal of Liver Diseases(Electronic Edition)

Effectiveness of potential antiviral treatments in COVID-19 transmission control:a modelling study

Background:Novel coronavirus disease 2019(COVID-19)causes an immense disease burden.Although public health countermeasures effectively controlled the epidemic in China,non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally.Vaccination is mainly used to prevent COVID-19,and most current antiviral treatment evaluations focus on clinical efficacy.Therefore,we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy.

Clinical observation of serum IL-18,IL-10 and sIL-2R levels in patients with chronic hepatitis Cpre-and post antiviral treatment

To discuss the roles of serum interleukin-18 (IL-18), interleukin-10 (IL-10) and soluble interleukin-2R (sIL-2R) in the pathogenesis of chronic hepatitis C and to observe the effects of interferon (IFN) on the above- mentioned serum cytokines Methods The levels of above- mentioned cytokines were detected in 10 healthy individuals, 24 asymptomatic hepatitis virus C (HCV) carriers and 27 patients with chronic hepatitis C ( before and after IFN treatment) using enzyme linked immunosorbent assay (ELISA) Results The levels of the cytokines in patients with chronic hepatitis C are higher than in healthy people (P<0 05) and in asymptomatic HCV carriers(P<0 05) The values of the cytokines show a significant positive correlation to ALT (P<0 05) Levels of tested cytokines decreased observably after IFN treatment (P<0 05) The grades of the serum levels for sIL-2R and IL-10 before IFN treatment (from high to low) were categorized accordingly: non-response group> partial- response group >complete- response group (P<0 05) Conclusions The tested cytokines co-participate in the pathogenesis of chronic hepatitis C, and can be used to evaluate the effect of IFN on the immune state of organisms Furthermore, sIL-2R and IL-10 are important for predicting the anti-viral efficacy of IFN

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography

BACKGROUND Integrating conventional ultrasound features with 2D shear wave elastography(2D-SWE)can potentially enhance preoperative hepatocellular carcinoma(HCC)predictions.AIM To develop a 2D-SWE-based predictive model for preoperative identification of HCC.METHODS A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital.The patients were divided into the modeling group(n=720)and the control group(n=164).The study included conventional ultrasound,2D-SWE,and preoperative laboratory tests.Multiple logistic regression was used to identify independent predictive factors for RESULTS In the modeling group analysis,maximal elasticity(Emax)of tumors and their peripheries,platelet count,cirrhosis,and blood flow were independent risk indicators for malignancies.These factors yielded an area under the curve of 0.77(95%confidence interval:0.73-0.81)with 84%sensitivity and 61%specificity.The model demonstrated good calibration in both the construction and validation cohorts,as shown by the calibration graph and Hosmer-Lemeshow test(P=0.683 and P=0.658,respectively).Additionally,the mean elasticity(Emean)of the tumor periphery was identified as a risk factor for microvascular invasion(MVI)in malignant liver tumors(P=0.003).Patients receiving antiviral treatment differed significantly in platelet count(P=0.002),Emax of tumors(P=0.033),Emean of tumors(P=0.042),Emax at tumor periphery(P<0.001),and Emean at tumor periphery(P=0.003).CONCLUSION 2D-SWE’s hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions,correlating significantly with MVI and antiviral treatment efficacy.

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade &#x0003e; 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.

Molecular diagnosis and treatment of drug-resistant hepatitis B virus

Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B(CHB).However,antiviral resistance remains an important challenge for long-term CHB therapy.All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase(RT),and all are reported to have resistant mutations.Since the hepatitis B virus(HBV)RT,like other viral polymerases,lacks proofreading activity,the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents.The molecular diagnosis of drug-resistant HBV is based on sequence variations,and current diagnostic methods include sequencing,restriction fragment polymorphism analysis,and hybridization.Here,we will discuss the currently available molecular diagnosis tools,in vitro phenotypic assays for validation of drug-resistant HBV,and treatment options for drug-resistant HBV.

Antiviral therapy in cytomegalovirus-positive ulcerative colitis:A systematic review and meta-analysis

AIM: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients.

Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to(pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response(SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte(CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

NS3 protease inhibitors for treatment of chronic hepatitis C: Efficacy and safety

A new treatment paradigm for hepatitis C is that the treatment must include an existing direct-acting antiviral agent, namely, a protease inhibitor(PI) combined with PEGylated interferon-a and ribavirin. The currently mar-keted PIs and PIs in clinical trials have different mecha-nisms of action. The development of new PIs aims for an improved safety profile and higher effectiveness. This article reviews NS3/4A protease inhibitors, focusing on major criteria such as their effectiveness and safety. Specific attention is paid to dosing regimens and adverse event profiles of PIs administered in clinical settings.

Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment and Consulting Doctor Later: A Retrospective Cohort Study

Objective:To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding.Methods:Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19(COVID-19)in Wuhan Union Hospital.We compared clinical features among patients with prolonged(a positive SARS-CoV-2 RNA on day 23 after illness onset)and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis.Results:Among 238 patients,the median age was 55.5 years,57.1%were female,92.9%(221/238)were administered with arbidol,58.4%(139/238)were given arbidol in combination with interferon.The median duration of SARS-CoV-2 virus shedding was 23 days(IQR,17.8-30 days)with a longest one of 51 days.The patients with prolonged virus shedding had higher value of D-dimer(P=0.002),IL-6(P<0.001),CRP(P=0.005)and more lobes lung lesion(P=0.014)on admission,as well as older age(P=0.017)and more patients with hypertension(P=0.044)than in those the virus shedding less than 23 days.Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol≥8 days after symptom onset[OR:2.447,95%CI(1.351-4.431)],≥3 days from onset of symptoms to first medical visitation[OR:1.880,95%CI(1.035-3.416)],illness onset before Jan.31,2020[OR:3.289,95%CI(1.474-7.337)].Arbidol in combination with interferon was also significantly associated with shorter virus shedding[OR:0.363,95%CI(0.191-0.690)].Conclusion:Duration of SARS-CoV-2 virus shedding was long.Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

Chronic hepatitis B in pregnant women: Current trends and approaches

Chronic hepatitis B(CHB)is a significant public health problem worldwide.The aim of the present review is to summarize the actual trends in the management of CHB in pregnant women.The prevalence of hepatitis B virus(HBV)infection in pregnant women is usually comparable to that in the general population in the corresponding geographic area.All women have to be screened for hepatitis B surface antigen(HBsAg)during pregnancy.Additional examinations of pregnant women with CHB may include maternal hepatitis B e antigen,HBV viral load,alanine aminotransferase level,and HBsAg level.The management of pregnancy depends on the phase of the HBV infection,which has to be determined before pregnancy.In women of childbearing age with CHB,antiviral therapy can pursue two main goals:Treatment of active CHB,and vertical transmission prevention.During pregnancy,tenofovir is the drug of choice in both cases.A combination of hepatitis B immunoglobulin and vaccine against hepatitis B should be administered within the first 12 h to all infants born to mothers with CHB.In such cases,there are no contraindications to breastfeeding.

Alterations of seminal and hormonal parameters:An extrahepatic manifestation of HCV infection?

AIM： To evaluate the possible influences of HCV infection and relative antiviral treatment on seminal parameters and reproductive hormonal serum levels. METHODS： Ten male patients with HCV-related chronic hepatitis and 16 healthy male volunteers were studied. In all subjects seminal parameters （nemaspermic concentration, progressive motility, morphology） and hormonal levels were determined. Seminal parameters and inhibin B, follicle-stimulating hormone, luteinizing hormone, total and free testosterone, estradiol, prolactine in patients were measured after six and twelve months of antiviral combined （interferon ± ribavirin） treatment. RESULTS： Patients before treatment showed a significantly lower nemaspermic motility and morphology as well as lower inhibin B and free testosterone levels than controls. Inhibin B levels in cases were improved six and 12 mo after treatment in five responders （161.9 ± 52.8 pg/mL versus 101.7 ± 47.0 pg/mL and 143.4 ± 46.1 pg/ mL versus 95.4 ± 55.6 pg/mL, respectively）. Hormonal pattern of patients did not significantly change after treatment, with the exception of estradiol levels with an initial reduction and an overall subsequent increment （19.7 ± 6.4 pg/mL versus 13.6 ± 5.0 pg/mL versus 17.3 ± 5.7 pg/mL）. However in 1-year responders a significant increment of free testosterone （14.2 ± 2.54 pg/mL versus 17.1 ± 2.58 pg/mL） occurred. An impairment of nemaspermic morphology occurred, while other seminal parameters did not change significantly during antiviral treatment. CONCLUSION： Patients with HCV infection show worse spermatic parameters than controls, suggesting a possible negative influence of virus on spermatogenesis, with further mild impairment during antiviral treatment. However therapy could improve the spermatic function, as suggested by the increased inhibin B levels and improved hormonal pattern in responders. Further studies are needed to confirm these preliminary intriguing results.

G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence

AIM:To evaluate the efficacy of granulocyte colony stimulating factors(G-CSF)in liver transplanted patients with hepatitis C(HCV)recurrence and Pegylated-IFN α-2b induced neutropenia,and to evaluate the impact of G-CSF administration on virological response. METHODS:Sixty-eight patients undergoing antiviral treatment for post-liver transplantation(OLT)HCV recurrence were enrolled.All patients developing neutropenia received G-CSF. RESULTS:Twenty three(34%)received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc(range 400-750/mmc);after 1 mo of G-CSF it increased to 1210/mmc(range 300-5590/mmc) (P<0.0001).Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation,infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis(P<0.003). CONCLUSION:G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasingneutrophil count,prolonging treatment and leading to sustained virological response(SVR)rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.