Relationship of hepatitis B virus infection to the recurrence of hepatocellular carcinoma after direct acting antivirals.

Recently, two conflicting articles about recurrence of hepatocellular carcinoma (HCC) after direct acting antivirals (DAA) against hepatitis C virus (HCV) were published. We investigated the relationship between DAA and HCC recurrence. Eligible patients were (1) history of HCC and treated curatively with interventions, and (2) interferon-free DAA therapy was initiated after eradication of HCC. We analyzed contributing factor for HCC recurrence. Ten out of 23 participants (43%) encountered recurrence of HCC. Age, sex, diabetes mellitus, fibrosis score, chemistry, and alpha-fetoprotein did not differ between patients with recurrence and patients without recurrence. The patients with recurrence had significantly higher values of antibody to hepatitis B core antigen (anti-HBc) than the patients without recurrence, 6.06±3.75 vs. 0.91±2.43 (p=0.0019). The relative risk of HCC recurrence comparing anti-HBc positive to negative was 5.2 (95% confidence interval 1.40 to 19.32). Odds ratio was 22.0 (95% confidence interval 2.5 to 191.1). We conclude that anti-HBc positivity was a strong contributing factor for HCC recurrence after DAA therapy.

Long-term evaluation of partial splenic embolization followed by interferon therapy in patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia.

OBJECTIVE: Patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia are often excluded from receiving interferon therapy because the treatment results in severe platelet depletion. Surgical splenectomy or partial splenic embolization (PSE) is a promising procedure for increasing the platelet count before interferon therapy. We performed PSE and evaluated the long-term clinical course in HCV cirrhotic patients. METHODS: Patients with HCV cirrhosis and thrombocytopenia were included (n=108) in this study. The straight-coiled PSE procedure (Takatsuka method) was performed. The platelet count, hemodynamic changes, rate of a sustained virological response (SVR) and prevalence of hepatocellular carcinoma (HCC) were evaluated. RESULTS: PSE resulted in a significant increase in the platelet count (before PSE: 7.9±2.3×10(4)/µL, two weeks after PSE: 16.7±6.6×10(4)/µL (p<0.001). Therefore, all participants were started on regular-dose interferon therapy. The SVR rate was 24% for serotype 1 and 62% for serotype 2. In the biochemical responders (BR) with SVR, the overall survival rate was 94.6% over five years and 89.3% over 10 years. In the non-responders (NR), the overall survival rate was 78.7% over five years and 62.2% over 10 years. The overall survival rate of the patients with SVR+BR was significantly higher than that observed in the patients with NR (p=0.0082). There were no differences in the prevalence of HCC between the patients with SVR+BR and NR. CONCLUSION: PSE enabled the induction of regular-dose interferon therapy in patients with HCV cirrhosis and thrombocytopenia. Although the prevalence of HCC did not differ between the SVR+BR and NR patients, there was a significant survival benefit in the patients with SVR+BR.

Dose volume histogram analysis of focal liver reaction in follow-up multiphasic CT following stereotactic body radiotherapy for small hepatocellular carcinoma.

PURPOSE: To investigate threshold dose (TD) of focal liver reaction (FLR) following stereotactic body radiotherapy (SBRT) for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. MATERIALS AND METHODS: In consecutive 50 patients receiving SBRT for small HCC, 38 patients receiving SBRT and follow up >6 months, FLR on follow-up CT had been previously studied. Patients with good concordance between FLR and highly irradiated area were eligible. Dose volume histogram (DVH) was used to identify TDs for FLR. Clinical factors were analyzed for correlation with TDs. RESULTS: Of 24 eligible patients, 23 had Child-Pugh score A and 1 scored B. Presence of FLR peaked at a median of 6 (range; 3-12) months. The median and 95% confidential intervals of TDs of pre-contrast and portal-venous phase CT were 32.4 Gy (30.3-35.4) and 34.4 Gy (31.9-36.0), respectively. Each median coefficient representing the concordance was 74.9% (range; 55.8-98.0%) and 80.5% (range; 70.8-92.4%), respectively. No clinical factors significantly correlated with the TDs. CONCLUSION: We proposed 30 Gy/5 fractions as TD of FLRs following SBRT for patients with HCC and liver cirrhosis. This TD will enable us to predict injured liver volume and to avoid complication beforehand from toxicity. Further pathological and clinical studies, in addition to more practical and precise data of DVH, are needed to clarify the significance of FLRs.

Two week induction of interferon-beta followed by pegylated interferon alpha-2b and ribavirin for chronic infection with hepatitis C.

OBJECTIVES: To elucidate the efficacy of interferon (IFN)-beta induction therapy followed by pegylated IFN alpha and ribavirin for chronic infection with hepatitis C virus (HCV). METHODS: Patients chronically infected with HCV genotype 1, high titer were enrolled. Twice daily bolus injections of 3 million units IFN-beta were administered for 14 days. Thereafter, weekly injection of pegylated IFN alpha 2b and daily intake of ribavirin were followed. Therapy duration was adjusted according to the response to the therapy. When time to an undetectable HCV-RNA was 1, 2, 4, 8, and 12 weeks, total duration of therapy was 12, 24, 36, 48 and 60 weeks, respectively. Patients who failed to achieve an undetectable HCV-RNA within 12 weeks discontinued therapy on 12 week. RESULTS: Among the 101 patients treated, 56 (55.4%) achieved sustained virological response (SVR). SVR rate for each treatment duration was 10/10 for 12 weeks, 12/14 for 24 weeks, 18/19 for 36 weeks, 15/26 for 48 weeks, 1/4 for 60 weeks and 0/28 for patients who discontinued therapy at 12 weeks. Mean time to an undetectable HCV-RNA was 35.5 +/- 2.7 days. Mean therapy duration was 27.3 +/- 1.4 weeks. Using a cut off value of 21.5 fmol/L of HCV core-antigen in the first week, SVR could be predicted by sensitivity of 0.91 and specificity of 0.78. CONCLUSION: IFN-beta induction therapy resulted in acceptable SVR rates despite short therapy duration. Steep reduction of HCV by IFN-beta enables us to predict SVR in the first week of therapy.

Partial splenic embolization reverses insulin resistance in patients with liver cirrhosis.

BACKGROUND: It is well known that patients with liver cirrhosis often develop insulin resistance and diabetes mellitus. Recently, we encountered a liver cirrhosis patient in whom partial splenic embolization (PSE) improved insulin sensitivity. Therefore, we conducted further investigation about PSE and insulin resistance. METHODS: Thirty-seven consecutive patients with liver cirrhosis underwent PSE. Hemodynamic changes, blood counts, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed before and 2 weeks after PSE. RESULTS: PSE resulted in decreased splenic venous flow and increased intestinal venous flow to the liver. Platelet counts before and after PSE were 7.7+/-0.5 x 10(4) /microL, 15.0+/-1.4 x 10(4) /microL, respectively (p<0.01). HOMA-IR before and after PSE were 6.5+/-2.1, 3.3+/-0.6, respectively (p<0.05). HCV core antigen before and after PSE were 6,340+/-1,296 fmol/L, 4,112+/-873 fmol/L, respectively (p<0.05). Conclusion PSE significantly reverses insulin resistance in patients with liver cirrhosis. The increase in intestinal venous flow to the liver and reduced HCV viral load were thought to be mechanisms of improvement in insulin sensitivity after PSE.