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.

Improving clinical outcomes of patients with hepatocellular carcinoma:Role of antiviral therapy,conversion therapy,and palliative therapy

In this editorial,I comment on three articles published in the recent issue of the World Journal of Gastrointestinal Oncology.Hepatocellular carcinoma(HCC)is an important public health concern,and there are three articles on the theme of HCC in this issue.I focus on the articles by Mu et al,Chu et al,and Ma et al for this editorial.While these articles may be considered as low-quality evidence,and the results cannot be generalized to non-hepatitis-B or C virus patients,the discussion of the results is important.In addition,though all the articles are from China,the relevance of the results is not minuscule.As resection is the main form of curative treatment modality owing to a donor liver shortage,surgeons need to be aware that preoperative long-course antiviral therapy can improve clinical outcomes by reducing postoperative liver dysfunction and recurrence of HCC following resection.Similarly,patients with super-giant HCC(defined as≥15 cm diameter)should also be carefully considered for liver resection,and if it is unresectable upfront,then a combination of liver-directed therapy and systemic therapy may downstage HCC.If,following downstaging,the patient qualifies for liver resection based on locally prevalent resectability criteria,then such therapy is labelled as conversion(from unresectable to resectable)therapy.In unresectable patients treated by a combination of treatment options,serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses,thus enabling personalized medicine.

Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy

Globally,hepatocellular carcinoma(HCC)is among the most prevalent and deadly cancers.Hepatitis B virus(HBV)infection is an important etiology and disease progression factor for HCC.Hepatectomy is a widely accepted curative treatment for HCC,but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection.Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy.However,many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently,necessitating the start of remedial antiviral therapy in the perioperative phase.Therefore,it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Hepatitis B Virus Infection in B-Cell Non-Hodgkin’s Lymphoma, and Effect of Entecavir in Prophylactic Antiviral Therapy

Background: specialized studies on hepatitis B virus (HBV) infection and B-NHL (B-cell Non-Hodgkin’s Lymphoma) are limited, as well as prophylactic antiviral therapy for B-NHL patients with HBV infection who are receiving anticancer chemotherapy. This study aims to investigate the association between HBV infection and B-NHL, and to evaluate the effect of prophylactic antiviral therapy for HBV-infected B-NHL patients. Study design: A retrospective, case-control study was performed. The study group included 420 patients with B-NHL who were consecutively diagnosed from May 2003 to October 2013 (age range, 14 - 71 years), and the control group included 1280 Chinese residents in Guangxi who participated in the Health Survey (age range, 18 - 74 years). We compared the prevalence rate of HBV infection and clinic-pathologic characteristics between the two groups. The prevalence rate of HBV infection in our study was 34.7% (146/420), higher than the prevalence rate of 13.9% (178/1280) in the general population (P < 0.001). Among 146 B-NHL patients who received anticancer chemotherapy, 104 patients (71.2%) received prophylactic antiviral therapy. Conclusion: This study provides evidence that HBV may play an important role in development of B-NHL. Entecavir maybe the better antiviral drugs than Lamivudine, and antiviral therapy is maintained more than 6 months that maybe the optimal duration of prophylactic antiviral therapy. But further investigation should be conducted for determination of optimal duration and monitoring of antiviral therapy.

Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies,respectively.Seven HCV-related studies,three HBV-related studies and three studies on HBV or HCV-related HCC were identified.RESULTS:A total of 1224 patients were included in this analysis.The estimated odds ratios(OR) for the 1-,2-,3-and 5-year recurrence were 0.54 [15.4% vs 24.1%,95% confidence interval(CI):0.32-0.89,P=0.02],0.42(36.9% vs 58.0%,95% CI:0.19-0.90,P=0.03),0.37(47.9% vs 63.8%,95% CI:0.19-0.71,P=0.003),and 0.32(66.7% vs 74.3%,95% CI:0.15-0.66,P=0.002),respectively;and the OR for the 1-,2-,3-,5-and 7-year mortality were 0.23(1.2% vs 9.1%,95% CI:0.07-0.71,P=0.01),0.31(6.4% vs 22.1%,95% CI:0.12-0.79,P=0.01),0.43(12.7% vs 20.8%,95% CI:0.21-0.89,P=0.02),0.42(25.1% vs 42.0%,95% CI:0.27-0.66,P=0.0002) and 0.28(31.9% vs 52.2%,95% CI:0.13-0.59,P=0.0008).CONCLUSION:This meta-analysis indicates the postoperative antiviral therapy,interferon in particular,may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after surgery.In patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC recurrence.It is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis B.However,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established.There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon.Interferon treatment reduces the overall incidence of HBV-related HCC in sustained re-sponders.However,side effects may limit its long-term clinical application.Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases.They may also improve the outcome after curative resection for HBV-related HCC.There are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC recurrence.After all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

Effects of antiviral therapy on preventing liver tumorigenesis and hepatocellular carcinoma recurrence

Chronic hepatitis B virus(HBV)infection is the key driving force of liver disease progression,resulting in the development of hepatic dysfunction,cirrhosis and hepatocellular carcinoma(HCC).The primary aim of therapy is to suppress or eliminate HBV replication to reduce the activity of hepatitis,thus reducing the risk of,or slowing the progression of,liver disease.Nucleos(t)ide analogues(Nucs)may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function,thus increasing survival in patients with hepatic decompensation.Long-term Nuc therapy may result in histological improvement or reversal of advanced fibrosis and reduction in disease progression,including the development of HCC.The long-term benefits of a finite course of interferon(IFN)-αtherapy also include a sustained and cumulative response,as well as hepatitis B surface antigen seroclearance and reduction in the development of cirrhosis and/or HCC.Pegylated IFN and newer Nucs may achieve better long-term outcomes because of improved efficacy and a low risk of drug resistance.However,treatment outcomes are still far from satisfactory.Understanding the effects of anti-HBV treatment against HCC incidence and recurrence after hepatectomy or liver transplantation is required for further improvement of outcome.

WJG 20^(th) Anniversary Special Issues(1): Hepatocellular carcinoma Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in AsianPacific regions.Antiviral therapy reduces,but does not eliminate the risk of HCC.It would be a heavy financial burden in most low and middle economic countries if all CHB patients received antiviral therapy and HCC surveillance.Thus,there is a need for accurate risk prediction to assist prognostication,decisions on the need for antiviral therapy and HCC surveillance.A few wellestablished risk factors for HCC,namely advanced age,male gender,high viral load,cirrhosis etc.,are the core components of three HCC risk scores:CU-HCC,GAGHCC and REACH-B scores.These 3 scores were confirmed to be accurate in predicting HCC up to 10 years in treatment-na ve patients.Their validity and applicability have recently been demonstrated in a large cohort of entecavir treatment patients.A decrease in risk scores after antiviral therapy translates to a lower risk of HCC.These findings support the application of HCC risk scores in all CHB patients.Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.Patients at risk of HCC should undergo regular HCC surveillance,even when they are receiving antiviral treatment.

Effects of HBV gene variations on disease development and antiviral therapy for patients with chronic hepatitis B

Viral variation may change pathogenicity, escape immunity, lead to persistence infection, and cause drug resistance against antiviral therapy. This study was undertaken to investigate the effects of HBV gene variation on the progression of disease and on the efficacy of antiviral therapy for patients with chronic hepatitis B(CHB). METHODS:Hepatitis B virus (HBV) gene mutational sites were detected using gene chip in selected hepatitis B patients. RESULTS:In the patients HBeAg did not show serologic conversion or HBeAg(-)/anti-HBe(+), but their HBV DNA remained positive 24 weeks after α-interferon therapy, which was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the patients, that HBV DNA levels decreased or were undetectable, but rebounded later after antiviral therapy by lamivudine was associated with mutations of aa528 and(or) aa552(i.e.YMDD mutation), which resulted in lamivudine-resistance. YMDD mutation was prone to occur 52 weeks after lamivudine therapy in some chronic hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764. CONCLUSIONS:HBV gene mutations could aggravate patient's condition and affect the efficacy of antiviral therapy. The regular detection of HBV gene mutation is helpful for identification of disease prognosis and adjustment of therapeutic strategy.

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.

Perioperative antiviral therapy for chronic hepatitis B-related hepatocellular carcinoma

BACKGROUND: After effective treatment with antiviral agent, patients with low serum hepatitis B virus (HBV) DNA level had a low incidence of hepatocellular carcinoma (HCC). HBV reactivation after HCC surgery is associated with HCC recurrence. To date, there are no universal guidelines for the perioperative antiviral treatment of patients with chronic hepatitis B, let alone antiviral therapy in patients with HBV-related HCC. The present analysis is trying to develop a perioperative anti-HBV treatment protocol. DATA SOURCES: A literature search of PubMed was performed, the key words were "perioperative" "antiviral therapy", "hepato-cellular carcinoma" and "chronic hepatitis B". All of the information was collected. RESULTS: Relevant documents showed that reactivation of HBV replication played a direct role in the late recurrence of HCC after surgical resection. The well control of viral load before and after operation significantly increased tumor-free survival. Many drugs are used in antiviral therapy including interferon alpha and nucleoside analogues. Foscarnet, two-agent or even multiagent of nucleoside analogues is necessary for perioperative antiviral treatment of patients with chronic hepatitis B related HCC. CONCLUSIONS: HBV reactivation after HCC surgery induces hepatitis flare and hepatocarcinogenesis, thus lifelong and vigorous control of HBV is very important in patients with chronic hepatitis B and HBV-related HCC. A uniform guideline is necessary to rapidly reduce HBV DNA to a lower level in perioperation.

Predictive factors associated with hepatitis C antiviral therapy response

Hepatitis C virus(HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000 s, dual therapy using a combinationof pegylated interferon plus ribavirin(PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors(boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response(SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.

RNA interference and antiviral therapy

RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.

Hepatitis C virus lymphotropism and peculiar immunological phenotype:Effects on natural history and antiviral therapy

Hepatitis C virus （HCV） has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ-and non-organ-specific autoantibody production up to overt non-Hodgkin＇s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. HCV infection of lymphoid ceils could set up privileged reservoirs able to interfere with the host viral clearance efficiency and may be implicated in viral recurrence after apparently successful antiviral therapy. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, easily detectable by searching simple laboratory and clinical parameters, mainly represented by vasculitis-like skin features and hypocomplementemia.The presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identified as a novel immunological cofactor. Further research is required to fully verify the real impact on therapeutic choice/regimen.

Direct acting antiviral therapy is curative for chronic hepatitis C/autoimmune hepatitis overlap syndrome

Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting antiviral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology.

Shear wave elastography in hepatitis C patients before and after antiviral therapy

AIMTo investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR). METHODSA total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (na&iuml;ve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE. RESULTSSW propagation velocity (Vs) was 1.23 &plusmn; 0.14 m/s in the control group, 1.56 &plusmn; 0.32 m/s in the SVR group, and 1.69 &plusmn; 0.31 m/s in the na&iuml;ve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the na&iuml;ve group (P = 0.01417). All four fibrosis markers were higher in the na&iuml;ve group than in the SVR group. In the na&iuml;ve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), &alpha; feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std &beta; = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std &beta; = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std &beta;= 0.2969, P = 0.03363). CONCLUSIONIn hepatitis C patients, liver stiffness is higher in treatment-na&iuml;ve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Until very recently, treatment for chronic hepatitis C virus(HCV) infection has been based on the combination of two non-viral specific drugs: pegylated interferon-α and ribavirin, which is effective in, overall, about 40%-50% of cases. To improve the response to treatment, novel drugs have been designed to specifically block viral proteins. Multiple compounds are under development, and the approval for clinical use of the first of such direct-acting antivirals in 2011(Telaprevir and Boceprevir), represents a milestone in HCV treatment. HCV therapeutics is entering a new expanding era, and a highly-effective cure is envisioned for the first timesince the discovery of the virus in 1989. However, any antiviral treatment may be limited by the capacity of the virus to overcome the selective pressure of new drugs, generating antiviral resistance. Here, we try to provide a basic overview of new treatments, HCV resistance to new antivirals and some considerations derived from a Public Health perspective, using HCV resistance to protease and polymerase inhibitors as examples.