Recurrence Of HCV-related Hepatocellular Carcinoma Research Articles

Advances in direct-acting antiviral therapy for liver transplant recipients with HCV-related hepatocellular carcinoma

The launch of direct-acting antiviral agents is a milestone in the treatment of hepatitis C, but further studies are needed to explore its specific timing and effectiveness in liver transplantation for HCV-related hepatocellular carcinoma (HCC). This article summarizes related guidelines, consensus statements, and recommendations in China and globally and the advantages of different treatment timing strategies. Furthermore, a retrospective analysis of related studies is performed to investigate the controversial topic of the impact of direct-acting antiviral agents on the recurrence rate of HCV-related HCC after liver transplantation, and it is pointed that direct-acting antiviral agents can reduce the risk of HCC recurrence in liver transplant recipients with HCV-related HCC. The selection of treatment timing should consider various factors such as liver function, waiting time for donors, and utilization of HCV-positive organs.

Timing of DAA Initiation After Curative Treatment and Its Relationship with the Recurrence of HCV-Related HCC.

Hepatitis C virus infection is a major cause of chronic hepatitis, leading to cirrhosis and hepatocellular carcinoma (HCC). Many studies agree that interferon (IFN)-based antiviral therapy can reduce the risk of HCC recurrence in patients with chronic hepatitis C who have achieved a sustained virological response (SVR). The recent introduction of direct-acting antivirals (DAA) has resulted in excitingly high SVR rates. However, as an IFN-free regimen, DAAs only exert antiviral activity without an immune response. The benefit of DAA-based regimens for HCC recurrence in patients with cirrhosis and following successful curative treatment remains controversial. Additionally, the time span between curative-intent therapy and the DAA regimen is an independent risk factor for HCC recurrence, irrespective of the DAA response. HCC patients who are eligible for potentially curative therapy by liver resection or ablation should defer DAA therapy; however, the accurate timing remains unclear. In this study, we reviewed the timing of DAA initiation after curative treatment and its effect on the recurrence of related HCC.

Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma recurrence

BackgroundThe impact of direct-acting antivirals (DAAs) remains a debate, whether they accelerate the recurrence rate of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative therapy. We evaluated the impact of direct-acting antiviral therapy on the rate of recurrence of HCV-related hepatocellular carcinoma following intervention in Egyptian patients.ResultsThe results of the study represented an HCC recurrence rate of 38% in patients who received direct-acting antiviral therapy after HCC intervention versus 62% in those who did not receive antiviral therapy. In group I, according to the Barcelona Clinic of Liver Cancer (BCLC) staging, a higher recurrence rate was observed (57.9%) among patients who were classified as BCLC stage B.ConclusionsHCC patients who did not receive direct-acting antiviral therapy after HCC intervention had a greater risk of HCC recurrence. DAAs did not increase the risk of HCC recurrence following HCC treatment; however, it did not abolish it. Close monitoring of patients after antiviral therapy is recommended.

Determination of candidate metabolite biomarkers associated with recurrence of HCV-related hepatocellular carcinoma

Hepatitis C virus (HCV) infection is associated with a high risk of developing hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to outcomes after curative therapy. In this study, we compared recurrent and non-recurrent HCC patients treated with radiofrequency ablation (RFA) in order to identify characteristic metabolic profile variations associated with HCC recurrence. Gas chromatography-mass spectrometry (GC-MS) -based metabolomic analyses were conducted on serum samples obtained before and after RFA therapy. Significant variations were observed in metabolites in the glycerolipid, tricarboxylic acid (TCA) cycle, fatty acid, and amino acid pathways between recurrent and non-recurrent patients. Observed differences in metabolites associated with recurrence did not coincide before and after treatment except for fatty acids. Based on the comparison of serum metabolomes between recurrent and non-recurrent patients, key discriminatory metabolites were defined by a random forest (RF) test. Two combinations of these metabolites before and after RFA treatment showed outstanding performance in predicting HCV-related HCC recurrence, they were further confirmed by an external validation set. Our study showed that the determined combination of metabolites may be potential biomarkers for the prediction of HCC recurrence before and after RFA treatment.

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.

Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

Second hepatectomy for recurrent hepatocellular carcinoma achieved sustained virological response to interferon therapy for hepatitis C.

Interferon (IFN) improves the prognosis of HCV-related hepatocellular carcinoma (HCC) in patients. However, the effects of IFN therapy for second hepatectomy (Hx) for recurrent HCC have not been established. Subjects included 96 patients who underwent a second Hx for recurrence of HCV-related HCC. Forty-four patients received IFN therapy past or postoperatively of the first Hx. Twenty of those patients attained a sustained viral response (SVR). The other 24 were non-responders (NR) and 52 patients who had not received IFN therapy (non-IFN) were classified as the NR/non-IFN group. Overall survival (SVR group vs. NR/non-IFN group: 5-yr, 91.7 vs. 51.0%; p = 0.012) and disease-free survival (SVR group vs. NR/non-IFN group: 3-yr, 64.7 vs. 25.9%; p = 0.006) rates were significantly different in both groups. By multivariate analysis, NR/non-IFN therapy, was the independent risk factor for overall survival (p = 0.025) and disease-free survival (p = 0.006) after second Hx. SVR achieved past or postoperatively of the first Hx of HCV-related HCC significantly inhibits recurrence and consequently improves patient survival after second Hx for recurrent HCC. Patients with SVR to IFN therapy would be good candidates for second Hx for recurrent HCC.

From the Editor’s desk...: October 2016

Oral DAA therapy is a major breakthrough in the treatment of hepatitis C virus (HCV) infection. In this issue of the Journal, two articles raise concerns about this therapy while two other provide relatively good news. In the first of the two “alarming” studies, Reig et al. show an unexpected early tumor recurrence in patients with HCV-related hepatocellular carcinoma (HCC) undergoing DAA therapy. HCC recurrence coincides with HCV clearance. In the second study providing bad news, Conti et al. show that in patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce occurrence of HCC, and patients previously treated for HCC have still a high risk of tumor recurrence, in the short term. In contrast, in a third study, Cheuk Men Cheung et al. find that DAA therapy in patients with decompensated cirrhosis leads to sustained improvement in liver function, with no evidence of increase in HCC development. Finally, The ANRS collaborative study group on hepatocellular carcinoma, by analyzing three distinct prospective cohorts, and a large number of patients, finds no increased risk of HCC recurrence after DAA therapy, in particular in those who underwent curative HCC treatment including liver transplantation. All these studies were performed in European countries. Together these studies indicate that there is an urgent need for large prospective studies, performed in different continents, evaluating the impact of DAA therapy on the risk of HCC, in particular, in patients with HCV-related cirrhosis.

Role of Insulin Resistance and Cytokeratin 18 on the Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

Background and study aim : Many studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). Caspase-generated cytokeratin-18 (CK-18) fragments are produced during apoptosis of hepatic cells. The present study aims to evaluate the value of serum CK-18 and the impact of insulin resistance on recurrence of HCV related HCC in patients treated with radiofrequency ablation (RFA). . Patients and Methods: The present study was conducted on 60 HCV patients. Group I: 30 patients with HCC treated by RFA and group II: 30 non HCC cirrhotic patients. Insulin resistance was estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) and CK-18 level was measured for all patients using ELISA. Results: HOMA-IR and CK-18 levels were significantly elevated in HCC patients when compared to non HCC cirrhotic patients. There was a significant increase in CK-18 and HOMA-IR levels in patients with local recurrence versus those with no recurrence (p<0.001). Univariate analysis revealed that HOMA-IR (p=<0.001) and CK-18 (p=<0.001) were significant predictors of recurrence of HCC. Conclusion: CK-18 and HOMA-IR are potential prognostic markers as they can predict the recurrence of HCC.

Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death in the world. With advances in imaging diagnostics, accompanied by better understanding of high-risk patients, HCC is now frequently detected at an early stage; however, the prognosis remains poor. The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs. This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence, especially with hepatitis C virus (HCV)-related hepatocellular carcinoma. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for the clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, transcatheter arterial chemoembolization, percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation) can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure. However, treatment strategies for recurrent disease are not mentioned in the BCLC classification. The strategy for recurrence may differ according to the recurrence pattern, i.e., intrahepatic distant recurrence vs multicentric recurrence. In this article, we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC, especially HCV-related HCC.

Loss of E-cadherin mRNA and gain of osteopontin mRNA are useful markers for detecting early recurrence of HCV-related hepatocellular carcinoma

We investigated whether expression of E-cadherin (E-cad) and osteopontin (OPN) mRNAs could predict the early recurrence of HCV-associated hepatocellular carcinoma (HCV-HCC) after curative surgery. Forty-four HCV-HCC patients who underwent curative hepatectomy were divided into three categories: category 1--recurrence (3 mR+: n = 6) or non-recurrence (3 mR-: n = 38) within 3 months; category 2--recurrence (6 mR+: n = 4) or non-recurrence (6 mR-: n = 34) between 3-6 months; category 3--recurrence (1 yR+: n = 4) or non-recurrence (1 yR-: n = 30) between 6-12 months. Levels of expression of E-cad and OPN mRNAs were analyzed quantitatively by real-time PCR and calculated using the formula: t = (copy of E-cad or OPN/copy of GAPDH) x 1,000. The t-value for E-cad was significantly lower in 3 mR+ than in 3 mR- (0.4 and 28.1, P < 0.05), in 6 mR+ than in 6 mR- (4.0 and 30.6, P < 0.05), and in 1 yR+ than in 1 yR- (9.2 and 32.9, respectively, P < 0.05). The t-value for OPN was higher in 3 mR+ than in 3 mR- (92.6 and 65.7, P = 0.57), in 6 mR+ than in 6 mR- (457.1 and 58.15, respectively, P = 0.24), and in 1 yR+ than in 1 yR- (221.8 and 53.5, respectively, P = 0.06). Low expression of E-cad mRNA and high expression of OPN mRNA are associated with a higher likelihood of early recurrence of HCV-HCC.