Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy

BACKGROUND/AIMS: According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. METHODS: The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. RESULTS: Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. CONCLUSIONS: Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.

A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function

BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. RESULTS: The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.

High-level Expression of Interleukin-17 and C-reactive Protein Predicts Tumor Progression in Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is the standard locoregional treatment in patients with unresectable hepatocellular carcinoma (HCC). Angiogenesis and inflammation play important roles in tumor growth in HCC. In this study, we evaluated the associations between the levels of growth factors and inflammatory markers and clinical prognosis in patients with unresectable HCC treated with TACE. METHODS: The clinical outcomes of 58 HCC patients treated with TACE at the Catholic Medical Centers from January, 2012 to February 2015 were evaluated. Baseline levels of the growth factors vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and hepatocyte growth factor and the inflammatory cytokines interleukin (IL)-17 and high sensitivity C-reactive protein (hs-CRP) were compared with the treatment outcomes. The primary endpoint was time to progression (TTP); the secondary endpoint was overall survival (OS). RESULTS: During the 20.8 months of follow-up, TTP was significantly delayed in patients with low levels of hs-CRP (≤0.15) and IL-17 (≤0.94) and a maximal tumor diameter ≤5 cm (P=0.010, P=0.015, and 0.048, respectively). Patients with HCC with low hs-CRP and IL-17 levels had a longer survival than that of those with high hs-CRP levels and IL-17 (35.1 vs. 22.5 months, P=0.000; 41 vs. 21.8 months, P=0.000, respectively). However, any baseline growth factors were not significantly correlated with TTP and OS. CONCLUSIONS: Elevated IL-17 and hs-CRP may be predictive of a poor outcome in patients with HCC treated with TACE. A better understanding of this relationship will require further investigation of the immune mechanisms underlying tumor progression.

Hemorheological Alteration in Patients Clinically Diagnosed with Chronic Liver Diseases

Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient’s history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P < 0.001) in male patients, but not in female patients. In correlation analysis, there were inverse relationships between both systolic and diastolic whole blood viscosity and liver stiffness (systolic: r = −0.25, diastolic: r = −0.22). Whole blood viscosity was significantly lower in male patients with LC than NAFLD or chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases.