Curative Treatment Of Hepatitis Research Articles

Abstract 13912: Insights From a Multi-Center Consortium for HCV-Viremic Donor Heart Transplant: Outcomes Are Excellent Across Regimens Often Without Major Changes to Statin or PPI

Introduction: With the availability of pangenotypic direct-acting antivirals (DAA) for facile, curative treatment of hepatitis C virus (HCV) infections, HCV-viremic donors are utilized regularly to partially address the shortage of suitable organs for heart transplant (HT). This multi-center, retrospective registry characterized HT outcomes from HCV-positive donors. Methods: Of 138 isolated HT recipients from 8 sites across the US, the most common DAAs were the pangenotypic antiviral combinations sofosbuvir-velpatasvir (SOF/VEL, n=39) and glecaprevir-pibrentasvir (GLE/PIB, n=76); these 115 cases were analyzed in terms of primary graft dysfunction (PGD), episodes of rejection ≥ pAMR1 and/or Grade 2R, post-transplant infection, sustained virologic response at 12 weeks post-treatment (SVR12), and survival up to 1 year. Results: Comparing these two most common pangenotypic regimens, HT recipients differed in their listing status (p<0.001), hospital stay length (p=0.04), time until HCV+ (p=0.01), DAA payor (p=0.01), induction therapy (p=0.03) and statin therapy (p=0.01). A concurrent open-label trial accounted for up to 13/39 SOF/VEL patients, partially accounting for differences in DAA payor. Despite potential interactions, statin and proton pump inhibitor (PPI) therapy typically continued uninterrupted with minimal dose adjustment. Both treatment groups showed 100% cure (SVR12) of donor-derived HCV. Although not powered for comparative effectiveness of DAA agents, there were no significant differences in study outcomes. SOF/VEL and GLE/PIB-treated patients demonstrated 97% and 96% survival at 1 year, respectively. Conclusions: As utilized to achieve cure of HT donor-derived HCV, two pangenotypic DAA regimens are safe and feasible, with coverage accessed across a variety of DAA payors. SVR12 can be achieved often without major modifications to PPIs or statins with either pangenotypic DAA regimen (with pravastatin most commonly utilized).

A214 SIMPLIFICATION OF CARE FOR HCV IS EFFECTIVE DURING THE COVID PANDEMIC: A RETROSPECTIVE STUDY OF HCV TREATMENT UTILIZING THE BRITISH COLUMBIA HEPATITIS C NETWORK

BackgroundThe COVID-19 pandemic has impacted healthcare access, including to curative treatment for hepatitis C (HCV) infection in the form of direct-acting antivirals (DAAs). A 49% decrease in DAA dispensations in Canada during the pandemic has been reported, but little is known about these treated populations.AimsTo explore the patient characteristics and treatment patterns in those who were treated for HCV during the COVID pandemic.MethodsA retrospective chart review was conducted at one site of utilizing the British Columbia Hepatitis C Network. Only patients included into the database were analyzed. Patients started on treatment between 03/17/2020-03/16/2021 were included as the “pandemic group” and patients from the 03/17/2019-03/16/2020 were included as a comparison “pre-pandemic group”. Data were extracted for clinicodemographic variables, laboratory investigations, treatment start date, regimen, and sustained virologic response at 12 weeks (SVR12).Results97 patients were treated during the pandemic compared to 143 patients the year prior, representing a 32% decline. Patients treated during the pandemic were predominantly new referrals (n=70, 72% vs n=64, 45% pre-pandemic, p<0.01) and had fewer total appointments (median 2 per patient vs 4 per patient pre-pandemic, p<0.01). There was a median of 1 in-person visit and 1 telehealth appointment per patient during the pandemic (vs median 2 per patient of each type pre-pandemic).Pandemic patients were younger (mean age 56.0 years vs 59.6 pre-pandemic, p=0.04), and a greater proportion were on opioid agonist therapy (28% vs 13% pre-pandemic, p<0.01). Less transient elastography (TE) was performed during the pandemic (69% vs 89% pre-pandemic). Amongst those with TE scores, a lower proportion of those treated during the pandemic were cirrhotic (13% vs 21% pre-pandemic).During the pandemic, treatment patterns shifted towards more prescriptions for glecaprevir/pibrentasvir (56% of all prescriptions vs 44% pre-pandemic) and sofosbuvir/velpatasvir (37% vs 29% pre-pandemic). There was slightly less use of sofosbuvir/velpatasvir/voxilaprevir at (2% vs 4% pre-pandemic).The proportion of patients who completed lab work for SVR was similar during the pandemic (n=83/97, 85.6%) compared to pre-pandemic (n=120/143, 83.9%). Similarly, SVR12 remained high during the pandemic at 98.7% (vs 99.3% pre-pandemic). Of all 97 patients prescribed DAAs during the pandemic, 92 (94.8%) completed treatment.ConclusionsLess persons were treated during the COVID pandemic, which may deter progress towards HCV elimination targets. Very high SVR12 and treatment completion rates during the pandemic suggest that patients can be effectively treated with less pre-treatment investigations and fewer appointments. Funding AgenciesNone

Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

The efficacies of entecavir and tenofovir in terms of enhancing prognosis after curative treatment of hepatitis B virus–related hepatocellular carcinoma

Background/aimsWhether entecavir (ETV) or tenofovir disoproxil fumarate (TDF) affords the better prognosis after curative treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. We compared recurrence and death rates between patients taking ETV and those taking TDF. MethodsBetween 2013 and 2017, patients with HBV-related HCC who had undergone hepatic resection (n=421) or radiofrequency ablation (n=305) as first-line anti-HCC treatment in three institutes were consecutively enrolled. All patients received ETV or TDF as a first-line antiviral. The cumulative probabilities of recurrence and death were assessed. We adjusted for viral factors, including the HBV-DNA load, and tumor and demographic factors. ResultsDuring the study period (median 46.6 [interquartile range 25.3–58.9] months), 227 patients experienced recurrence and 53 died. In the ETV (n=405) and TDF (n=321) groups, the annual incidences of recurrence (10.61 and 11.21 per 100 person-years, respectively; P=727) and death (2.28 and 1.79 per 100 person-years, respectively; P=277) were similar, with adjusted hazard ratios (aHRs) of 0.932 (P=0.622) and 0.667 (P=0.193), respectively. When stratified by treatment modality and the timing of antiviral therapy commencement, the values were similar (all P>0.05). Inverse probability of treatment weighting (IPTW) analyses yielded results that were similar in the two groups in terms of recurrence (aHR=1.038, P=0.963) and death (aHR=0.799, P=0.431). Furthermore, the early (<2 years) and late (≥2 years) recurrence risks were not statistically different in the two groups (both P=0.400), as confirmed by IPTW analysis (P=0.502 and P=0.377, respectively). ConclusionsThe prognoses in terms of recurrence and death after curative treatment of HBV-related HCC were not statistically different between the ETV and TDF groups. Further validation studies are needed.

SAT268 - Proteomic identification of serum factors that correlate with reduction of HVPG following curative treatment for hepatitis C virus infection

SAT268 - Proteomic identification of serum factors that correlate with reduction of HVPG following curative treatment for hepatitis C virus infection

Antiviral therapy to reduce hepatocellular carcinoma recurrence in patients with low HBV-DNA levels: A randomized controlled trial.

1510 Background: Despite antiviral treatment has been shown to reduce hepato- cellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. Methods: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were ran- domly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P 1/4 0.016, P 1/4 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409– 0.884; P 1/4 0.010] and 0.509 (95% CI, 0.333–0.778; P 1/4 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recur- rence (hazard ratio [HR] 1/4 0.316, 95% CI 0.157 – 0.637; P 1/4 0.001) but not of early tumor recurrence (HR 1/4 0.782, 95% CI, 0.493–1.240; P 1/4 0.296). Conclusions: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection. Clinical trial information: ChiCTR-IPR-15006587.

Antiviral Therapy Reduces Hepatocellular Carcinoma Recurrence in Patients With Low HBV-DNA Levels: A Randomized Controlled Trial.

Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409-0.884; P = 0.010] and 0.509 (95% CI, 0.333-0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157-0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493-1.240; P = 0.296). In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.

The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy.

To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups. We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN-free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.

Entecavir and tenofovir reduce hepatitis B virus-related hepatocellular carcinoma recurrence more effectively than other antivirals.

Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n=261), group B (low-potency NA; n=90) and group C (high-potency NA; n=256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2months in groups A, B and C, respectively (P<.001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR]=0.39, P<.001) and group B (adjusted HR=0.47, P<.001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR=0.46, P<.001) and group B (adjusted HR=0.59, P=.007). Group C had significantly lower risk of viral breakthrough than group B (HR=0.19, P<.001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR=2.03, P=.007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.

소라페닙 투여 간세포암종 환자에서 항바이러스제 치료의 생존이득

Background/Aims: Nucleos(t)ide analogues (NAs) help reduce the recurrence rate after the curative treatment of hepatitis B related hepatocellular carcinoma (HCC). Sorafenib has been shown to improve survival of advanced HCC patients. Whether antiviral therapy with NAs could help such patients is unknown. Our aim is to investigate the usefulness of antiviral therapy for advanced-stage HCC treated with sorafenib. MethodsWe performed a retrospective cohort study in advanced-stage HCC patients treated with sorafenib between June 2007 and December 2013. Patients in group A (the nonantiviral therapy group) were treated with sorafenib alone. Those in group B (the antiviral therapy group) were treated with sorafenib and NAs. Progression-free survival (PS) and overall survival (OS) were compared between these two groups. ResultsFinally, 23 patients in group A and 40 patients in group B were enrolled in the study. The mean number of days of treatment with sorafenib was 79 (34-231) days and 96 (33-449) days for group A and B, respectively (P=0.286). The mean PS of group A and B was 97 (14-449) days and 51 (0-461) days, respectively (P=0.068). The OS was 154 (44-741) days in group A and 138 (30-1,025) days in group B (P=0.665). PS and OS showed no significant difference between the two groups. ConclusionsThis study shows that there was no significant survival gain of using antiviral therapy in patients with advanced-stage HCC treated with sorafenib. In consideration of costeffectiveness, antiviral therapy may be not mandatory. (J Liver Cancer 2016;16:23-30)

Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor.

Whether an antiviral interferon (IFN)-based therapy (IBT) after curative treatment of hepatocellular carcinoma (HCC) improves the prognosis in patients with hepatitis C virus (HCV)-related HCC remains to be elucidated. A total of 178 patients within the Milan criteria underwent curative treatment for HCV-related HCC. Both the time to beyond the Milan criteria (TTBMC) and overall survival (OS) were compared between the sustained virologic response (SVR) (IFN with SVR, n = 22), non-SVR (IFN without SVR, n = 19), and non-IBT (control, n = 82) groups using propensity score matching analysis. Prognostic factors to predict survival were also determined by the Cox proportional-hazards model. TTBMC in the IFN with SVR group was significantly longer than those in the control and IFN without SVR groups (P < 0.001 and P = 0.006, respectively), although no significant difference existed between the IFN without SVR and control groups. Similarly, OS of the IFN with SVR group was significantly longer than that of the control and IFN without SVR groups (P < 0.001 and P = 0.029, respectively), although no significant difference existed between the IFN without SVR and control groups. The Cox proportional-hazards model identified SVR as an independent prognostic factor in these patients. The IFN with SVR group showed a 0.096-fold decrease in mortality risk compared with the control group (95% confidence intervals = 0.023-0.405; P = 0.001). Elimination of HCV after curative treatment of patients with HCC within the Milan criteria inhibits recurrence and contributes to a preferential prognosis.

Effect of previous interferon-based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma.

Previous reports have shown that interferon (IFN)-based therapy decreases the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. However, it remains to be fully elucidated whether elimination of HCV by IFN-based therapy inhibits HCC recurrence after curative treatment, such as surgical resection and local ablation therapies. In this study, we aimed to clarify the influence of a sustained virological response (SVR) after IFN-based therapy on recurrence and survival after curative treatment of HCC. Fifty-one patients who underwent curative treatment of HCV-related HCC after receiving IFN-based therapy were analyzed retrospectively. They were classified into SVR (N = 14) and non-SVR groups (N = 37). In the SVR group, serum levels of aspartate aminotransferase and alanine aminotransferase, the indocyanine green retention rate at 15 min, and the percentages of patients with liver cirrhosis and HCV serotype 1 were significantly lower, whereas serum albumin level and platelet count were significantly higher upon HCC occurrence. Recurrence-free survival (RFS) for the first recurrence was significantly higher in the SVR group (P < 0.01). Multivariate analysis showed that SVR at initial HCC treatment (P < 0.01) and multiple tumors (P < 0.01) are prognostic factors for RFS. Moreover, RFS for the second recurrence showed a similar trend to that for the first recurrence. In conclusion, patients who underwent IFN-based therapy before initial curative treatment of HCC had a favorable clinical outcome compared with non-SVR patients.

Antiviral therapy after curative treatment of hepatitis B/C virus‐related hepatocellular carcinoma: A systematic review of randomized trials

Available published work on the benefit of adjuvant antiviral therapy after curative treatment of hepatocellular carcinoma (HCC) reports controversial results. The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event outcomes with 95% confidence intervals using RevMan 5. We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group compared with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed.

Effects of antiviral therapy on long‐term outcome after liver resection for hepatitis B virus‐related hepatocellular carcinoma

We investigated the effects of nucleos(t)ide analogues (NAs) on long-term outcome in patients following curative treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study involved 70 of the 76 patients who had undergone liver resection for HBV-related HCC in our department; 6 patients were excluded due to non-curative resection or advanced cancer. The 70 patients were divided into three groups, as follows: 13 patients with high serum concentration of HBV DNA (≥4log(10)copies/mL) and no antiviral therapy (high viral group); 46 patients who received antiviral therapy during the serial follow up (antiviral therapy group) because of high viral concentration (≥4log(10)copies/mL); and 11 patients with low serum concentration of HBV DNA (<4log(10)copies/mL) and no antiviral therapy (low viral group). Tumor-free survival rate was significantly higher in the low viral group than in the high viral group (P=0.0058). Multivariate analysis revealed that a high serum concentration of HBV DNA (≥4log(10)copies/mL) (risk ratio 6.717, 95% confidence interval 1.435-31.434, P=0.0156) was an independent risk factor for a short tumor-free survival time. Tumor-free survival rate was significantly higher in the antiviral therapy group than in the high viral group (P=0.0478). Multivariate analysis revealed that presence of multiple tumors (risk ratio 2.857, 95% confidence interval 1.403-5.816, P=0.0038) was an independent risk factor for a short tumor-free survival time. The cumulative survival rate was significantly higher in the antiviral therapy group than in the high viral group (P=0.0025). Multivariate analysis revealed that not undergoing antiviral therapy (risk ratio 0.121, 95% confidence interval 0.024-0.608, P=0.0104) was an independent risk factor for a short survival time. A high serum concentration of HBV DNA (≥4log(10)copies/mL) was a strong risk factor for HCC recurrence after resection of HBV-related HCC. Antiviral therapy with NAs improved the long-term outcome after resection of HBV-related HCC in patients with high serum concentrations of HBV DNA.

Effect of Previous Interferon Treatment on Outcome After Curative Treatment for Hepatitis C Virus-Related Hepatocellular Carcinoma

Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) prevents the development of hepatocellular carcinoma (HCC). The purpose of this study was to clarify the effect of previous IFN treatment before the development of HCC on recurrence and survival in HCV-related HCC patients. Three hundred ninety-five patients who underwent curative treatment for HCV-related HCC were enrolled. Of these, 124 had received IFN treatment before the development of HCC (17 achieved sustained virological response [SVR group] and 107 did not [non-SVR group]), whereas 271 patients had never received IFN treatment (IFN-untreated group). The first and second recurrence and survival rates in these patient groups were statistically analyzed. The first HCC recurrence rate was similar among patient groups. In contrast, the second HCC recurrence rate was significantly lower in the SVR group than in the non-SVR group (p = 0.003) and the IFN-untreated group (p = 0.006). In multivariate analysis, platelet count (p = 0.033) and number of tumors (p = 0.001) were associated with the first HCC recurrence, while SVR (p = 0.002) was the only factor associated with the second HCC recurrence. The survival rate was higher in the SVR group than in non-SVR and IFN-untreated groups, and SVR to previous IFN treatment was an independent factor associated with better survival (p < 0.001). SVR to previous IFN treatment before the development of HCV-related HCC was associated with lower risk of the second recurrence of HCC and better survival.

IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatocellular carcinoma

The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein >30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma

The role of anti-viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined. To investigate the role of anti-viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)-related HCC. A systematic electronic search on keywords including HCC and different anti-viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV-related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality. Nine cohort studies were included with a total number of 551 patients: 204 patients with anti-viral treatment group and 347 patients without anti-viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti-viral treatment group (55% vs. 58%; odds risk (OR)=0.59, 95% CI 0.35-0.97, P=0.04). The risk of HCC was reduced by 41% in the anti-viral treatment group. There were also significant differences in favour of anti-viral treatment group in terms of liver-related mortality (0% vs. 8%; OR=0.13, 95% CI 0.02-0.69, P=0.02) and overall mortality (38% vs. 42%; OR=0.27, 95% CI 0.14-0.50, P<0.001). Anti-viral therapy has potential beneficial effects after the curative treatment of HBV-related hepatocellular carcinoma in terms of tumour recurrence, liver-related mortality and overall survival. Anti-viral therapy should be considered after curative treatment of hepatocellular carcinoma.

Effect of pegylated interferon therapy on intrahepatic recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma

We wished to determine whether pegylated interferon (PEG-IFN) therapy after curative treatment of hepatocellular carcinoma (HCC) prevents a recurrence of HCC. Thirty-seven HCC patients with hepatitis C virus (HCV) infection who were treated with PEG-IFN after curative treatment (PEG-IFN group) and 145 controls without IFN therapy (non-IFN group) were enrolled. The overall survival and recurrence-free survival rates were compared between the groups, and the predisposing factors for recurrence and survival were analyzed. The rates were also examined by propensity score (PS) matched analysis that could minimize selection biases. The median follow-up period was 3.7 years. The 5-year survival rate in the PEG-IFN group (91%) was significantly higher than that in the non-IFN group (56%; P < 0.01). The rate of the second recurrence but not that of the first recurrence of HCC in the sustained virological responder (SVR) group was lower than that in the non-IFN group (P = 0.03). Improvement of survival by PEG-IFN and low rate of second recurrence in the SVR group were also observed in PS matched analysis. Multivariate analysis revealed that PEG-IFN therapy and high serum albumin were good prognostic factors for survival. Although low serum albumin and large and multiple tumors were risk factors for the first recurrence, non-SVR and low serum albumin were risk factors for the second recurrence. PEG-IFN-therapy after curative treatment of HCC improved the rate of survival, and SVR was found to be closely correlated with the prevention of recurrence.

Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma

Various clinical studies have indicated that interferon (IFN)-alpha treatment prevents the development of hepatocellular carcinoma (HCC) in people chronically infected with hepatitis C virus. However, it has been controversial whether IFN-alpha treatment prevents HCC recurrence. The aim of this study was to identify the preventive effect of IFN-alpha treatment after curative therapy of primary tumours within the Milan criteria (three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less) on HCC recurrence. We conducted a meta-analysis of five trials including 355 patients (167 patients received IFN-alpha treatment after curative therapy of primary tumours) and estimated relative risks (RRs) and 95% confidence intervals (CIs) for the effect of IFN-alpha on HCC recurrence according to the DerSimonian and Laird method. IFN-alpha treatment after curative therapy of primary tumours significantly prevented HCC recurrence (RR 0.33; 95%CI 0.19-0.58, P < 0.0001) without a significant heterogeneity (Q = 4.52, P = 0.34). An evaluation using the Begg method suggested no evidence of publication bias. Sub-group analyses revealed that IFN-alpha treatment reduced HCC recurrence in two studies achieving sustained virologic response (SVR) rates >30% (RR 0.20; 95%CI 0.05-0.81, P = 0.02) and in three studies achieving SVR rates <or=30% (RR 0.44; 95%CI 0.23-0.84, P = 0.01). In conclusion, IFN-alpha treatment after curative treatment of primary tumour within Milan criteria may be effective for the prevention of HCC recurrence, and higher SVR rate may be associated with better preventive effect of IFN-alpha treatment on HCC recurrence.

Effects of a 24-week course of interferon-α therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma

To assess whether a 24-wk course of interferon (IFN) could prevent hepatocellular carcinoma (HCC) recurrence and worsening of liver function in patients with hepatitis C virus (HCV)-infected patients after receiving curative treatment for primary HCC. Outcomes in 42 patients with HCV infection treated with IFN-alpha, after curative treatment for primary HCC (IFN group), were compared with 42 matched curatively treated historical controls not given IFN (non-IFN group). Although the rate of initial recurrence did not differ significantly between IFN group and non-IFN group (0%, 44%, 61%, and 67% vs 4.8%, 53%, 81%, and 87% at 1, 3, 5, and 7 years, P = 0.153, respectively), IFN group showed a lower rate than the non-IFN group for second recurrence (0%, 10.4%, 28%, and 35% vs 0%, 30%, 59%, and 66% at 1, 3, 5 and 7 years, P = 0.022, respectively). Among the IFN group, patients with sustained virologic response (SVR) were less likely to have a second HCC recurrence than IFN patients without an SVR, or non-IFN patients. Multivariate analysis identified the lack of SVR as the only independent risk factor for a second recurrence, while SVR and Child-Pugh class A independently favored overall survival. Most intrahepatic recurrences of HCV-related HCC occurred during persistent viral infection. Eradication of HCV is essential for the prevention of HCC recurrence and improvement of survival.