Past,present,and future of long-term treatment for hepatitis B virus

The estimated world prevalence of hepatitis B virus(HBV)infection is 316 million.HBV infection was identified in 1963 and nowadays is a major cause of cirrhosis and hepatocellular carcinoma(HCC)despite universal vaccination programs,and effective antiviral therapy.Long-term administration of nucleos(t)ide analogues(NA)has been the treatment of choice for chronic hepatitis B during the last decades.The NA has shown a good safety profile and high efficacy in controlling viral replication,improving histology,and decreasing the HCC incidence,decompensation,and mortality.However,the low probability of HBV surface antigen seroclearance made necessary an indefinite treatment.The knowledge,in recent years,about the different phases of the viral cycle,and the new insights into the role of the immune system have yielded an increase in new therapeutic approaches.Consequently,several clinical trials evaluating combinations of new drugs with different mechanisms of action are ongoing with promising results.This integrative literature review aims to assess the knowledge and major advances from the past of hepatitis B,the present of NA treatment and withdrawal,and the future perspectives with combined molecules to achieve a functional cure.

Current and future antiviral drug therapies of hepatitis B chronic infection

Despite significant improvement in the management of chronic hepatitis B virus(HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon(IFN)-α and monotherapy with five nucleos(t)ide analogues(NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B:Results of an open,controlled trial

AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

Efficacy of 3 years of adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance

AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM).

Efficacy and cost-effectiveness of antiviral regimens for entecavir-resistant hepatitis B:A systematic review and network meta-analysis

Background:Chronic hepatitis B(CHB)patients who had exposed to lamivudine(LAM)and telbivudine(LdT)had high risk of developing entecavir(ETV)-resistance after long-term treatment.We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance.Data sources:We searched PubMed,EMBASE and Web of Science for studies on nucleos(t)ide analogues(NAs)treatment[including tenofovir disoproxil fumarate(TDF)-based rescue therapies,adefovir(ADV)-based rescue therapies and double-dose ETV therapy]in CHB patients with ETV-resistance.The network meta-analysis was conducted for 1-year complete virological response(CVR)and biological response(BR)rates using GeMTC and ADDIS.A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate.Results:A total of 6 studies were finally included in this analysis.The antiviral efficacy was estimated.On network meta-analysis,the 1-year CVR rate in ETV-TDF[odds ratio(OR)=22.30;95%confidence interval(CI):2.78-241.93],LAM-TDF(OR=70.67;95%CI:5.16-1307.45)and TDF(OR=16.90;95%CI:2.28-186.30)groups were significantly higher than that in the ETV double-dose group;the 1-year CVR rate in the LAM-TDF group(OR=14.82;95%CI:1.03-220.31)was significantly higher than that in the LAM/LdTADV group.The 1-year BR rate of ETV-TDF(OR=28.68;95%CI:1.70-1505.08)and TDF(OR=21.79;95%CI:1.43-1070.09)therapies were significantly higher than that of ETV double-dose therapy.TDFbased therapies had the highest possibility to achieve the CVR and BR at 1 year,in which LAM-TDF combined therapy was the most effective regimen.The ratio of cost/effectiveness for 1-year treatment was 8526,17649,20651 Yuan in the TDF group,TDF-ETV group,and ETV-ADV group,respectively.Conclusions:TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.

Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

Novel approaches towards conquering hepatitis B virus infection

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-&#x003b1; inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Does antiviral therapy reduce complications of cirrhosis?

Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient&#x02019;s serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure.

Search for a cure for chronic hepatitis B infection: How close are we?

Chronic hepatitis B(CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferonbased therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future.

Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

水芹水醇提取物在雏鸭体内对DHBV-DNA的抑制效果

目的观察水芹(Oenanthe Javanica,OJ)水醇提取物在鸭体内对鸭乙型肝炎病毒(DHBV)-DNA 的抑制效果.方法将 DHBV 感染雏鸭随机分为高、中、低三个剂量组,分别为8,5,3g/kg 组进行药物治疗.每组5～6只,ig,2次/d×10 d;设病毒对照组(DHBV),以生理盐水(NS)代替药物,ig,2次/d×10 d.阳性药用阿昔洛韦(ACV)粉剂250 mg,ig,100mg/kg,2次/d×10 d.在感染7d 后,即用药前(TO),用药后5d(T5),用药10 d(T10)和停药后3 d(P3),自鸭腿胫静脉分别取血,分离血清,检查 DHBV-DNA 水平和肝功能.治疗结束经颈静脉放血处死动物,分别切取雏鸭肝脏,作肝病理检查.结果三批实验结果表明,水芹水醇提取物中,高剂量组对感染雏鸭无毒性,给药5,10 d 能显著降低 DHBV 感染鸭血清DHBV-DNA 水平,即 d5的测定值由1.04分别下降至0.52和0.44,抑制率分别为50.0%和50.6%;d10由0.85分别下降0.42和0.36,抑制率分别为57.7%和57.6%,与病毒对照组比较,均有显著性差异(P<0.05和 P<0.01).低剂量组对鸭血清 DHBV-DNA 也有一定疗效,并显示明显的量效关系.肝功能改善明显,给药10 d,中剂量雏鸭血中 ALT,AST,SB 含量下降率分别为44.1%,44.2%,33.3%.高剂量的下降率分别为61.0%,58.3%,64.4%.低剂量虽对肝功能有改善,但无统计显著性.肝组织病理观察证实,中、高剂量对雏鸭肝脏均有保护作用,肝细胞变性坏死均较轻,肝小叶结构基本完整.结论 OJ 在雏鸭体内有抗 DHBV 的作用,保肝效果显著.

干扰素α-2b联合阿德福韦酯治疗慢性乙型肝炎疗效观察

目的探讨干扰素(IFN)α-2b联合阿德福韦酯(ADV)治疗慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效。方法 47例CHB患者随机分为2组,IFNα-2b联合ADV组(联合用药组)22例,单用ADV组(单药组)25例。监测2组患者治疗12、24、48、96周的HBV DNA水平、HBV血清标志物及ALT变化。结果治疗48周时,联合用药组患者血清中HBV DNA转阴率和ALT复常率明显高于单药组,联合用药组在停用IFNα-2b48周后上述指标仍高于单药组。治疗48周时,联合用药组完全应答率为59%,高于单药组的28%(P<0.05)。结论IFNα-2b联合ADV治疗CHB优于单用ADV,可提高HBeAg/抗HBe血清学转换率及完全应答率。

安络化纤丸联合干扰素α-1b治疗慢性乙型肝炎肝纤维化疗效观察

目的观察安络化纤丸联合干扰素(interferon,IFN)α-1b(运德素)治疗慢性乙型肝炎(乙肝)肝纤维化的疗效。方法将129例慢性乙肝肝纤维化患者随机分为安络化纤丸组(AL组)40例、IFNα-1b组(IFN组)43例和安络化纤丸联合IFNα-1b组(AL+IFN组)46例。3组患者在治疗0、24、48周及停药24周时采用放射免疫分析法检测血清肝纤维化指标水平,同时观察患者临床症状,监测肝功能、乙肝标志物、HBV DNA滴度和肝脏影像学变化等指标,对各治疗组(每组3例)患者进行肝脏活体组织检查,观察肝脏病理变化。结果 AL组、IFN组、AL+IFN组3组比较,治疗48周时总有效率分别为70.0%、72.0%、91.3%;停药24周随访时总有效率分别为75.0%、74.4%、86.9%,AL+IFN组优于AL组和IFN组(P均<0.05)。AL+IFN组治疗后PCⅢ、HA、CⅣ、LN水平较治疗前显著下降(P均<0.05);AL+IFN组与AL组、IFN组治疗后及随访时比较,PCⅢ、HA、CⅣ、LN水平也降低明显(P均<0.05)。在治疗48周时、停药24周时,AL+IFN组HBeAg阴转率和HBV DNA阴转率高于AL组(P均<0.05)。AL+IFN组与IFN组同期比较,差异无统计学意义。结论安络化纤丸联合IFNα-1b较安络化纤丸单用具有更好的抗肝纤维化、抗病毒和改善肝功能的作用,可能更有利于阻断慢性乙肝的发展。

恩替卡韦治疗血清HBeAg阳性高病毒载量乙型肝炎病毒携带者合并肺结核患者预防抗痨治疗引起的药物性肝损伤效果研究

目的探讨在抗痨治疗过程中应用恩替卡韦预防治疗血清HBeAg阳性高病毒载量的乙型肝炎病毒(HBV)携带者合并肺结核(PTB)患者对预防药物性肝损伤(DILI)的效果。方法2019年1月~2022年1月我院收治的96例血清HBeAg阳性高病毒载量的HBV携带者合并PTB患者,被随机分为观察组48例和对照组48例。两组均接受标准的抗痨治疗,观察组在抗痨治疗的基础上应用恩替卡韦进行预防性抗HBV治疗,均持续治疗6个月。采用PCR-荧光免疫探针法检测血清HBV DNA载量。结果在治疗1个月、3个月和6个月,观察组DILI累计发生率分别为12.5%、16.7%和18.8%,显著低于对照组的29.1%、45.8%和54.2%(P<0.05);在治疗3个月,8例观察组发生DILI患者血清ALT、AST和HBV DNA水平分别为(67.7±8.5)U/L、(57.1±4.7)U/L和(1.1±0.2)lg IU/mL,均显著低于22例对照组【分别为(104.5±13.9)U/L、(96.9±15.3)U/L和(6.6±1.4)lg IU/mL,P<0.05】;在治疗过程中,观察组肝区不适、胃肠道症状、血清肌酸激酶升高、药疹和中止抗痨等不良反应发生率为10.4%,显著低于对照组的27.1%(P<0.05);在治疗结束时,观察组均获得治愈(100.0%),而在对照组治愈41例(85.4%,P<0.05),其中7例患者在延长疗程后才获得PTB的治愈。结论应用恩替卡韦可有效降低血清HBeAg阳性高病毒载量的HBV携带者合并PTB患者在抗痨治疗过程中DILI发生率,保证抗痨治疗的顺利进行,而使患者获益。

从“HBF drug watch”看抗HBV药物研制的现状及进展

乙型肝炎病毒(hepatitis B virus,HBV)是全球公众健康的首要危险因素,目前现有的抗病毒治疗方案只能抑制HBV复制,不能完全根除HBV.由于抗丙型肝炎病毒(hepatitis C virus,HCV)的直接抗病毒药物(direct antiviral agents,DAAs)陆续上市,国外许多大的制药公司转向投入抗HBV药物研制.近两年登陆http://www.hepb.org/professionals/hbf_drug_watch.htm网站,抗HBV药物研制更新较以前明显增快.本文将在上述网站上可以查证到的已上市和在研究的抗HBV药物种类、作用机制及未来市场前景进行简要述评及总结.