Lusutrombopag Reduces the Risk of Hemoperitoneum Caused by Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma Compared with Platelet Transfusion.

INTRODUCTION: Patients with liver cirrhosis develop thrombocytopenia and an increased risk of bleeding events after invasive procedures. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count. This study assessed whether lusutrombopag reduces the risk of hemoperitoneum following percutaneous radiofrequency ablation for hepatocellular carcinoma, compared with platelet transfusion. METHODS: Participants in the present study comprised patients with severe thrombocytopenia (platelet count <50,000/µL) enrolled between November 2012 and March 2020, excluding patients with idiopathic thrombocytopenia or anticoagulant use. Hemoperitoneum rate, hemostasis rate, hemoglobin reduction rate, rate of achieving a platelet count ≥50,000/µL, and increases in platelet count and factors contributing to hemoperitoneum were retrospectively analyzed. RESULTS: This study enrolled 41 patients, comprising 18 patients administered lusutrombopag and 23 patients who received platelet transfusion. The major hemoperitoneum rate after RFA was tend to be lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%). All of the major hemoperitoneum was observed in the platelet transfusion group. Hemoglobin reduction rate was lower in the lusutrombopag group (-0.17%) than in the platelet transfusion group (6.79%, p = 0.013). Hemostasis rate was lower in the lusutrombopag group (0%) than in the platelet transfusion group (21.7%, p = 0.045). The rate of achievement of platelet counts ≥50,000/µL the day after RFA was higher in the lusutrombopag group (100%) than in the platelet transfusion group (60.9%, p = 0.005). CONCLUSION: Lusutrombopag may be able to perform RFA more safely with respect to the hemoperitoneum caused by percutaneous radiofrequency ablation compared with platelet transfusion.

Feeding artery ablation before radiofrequency ablation for hepatocellular carcinoma may reduce critical recurrence.

BACKGROUND AND AIM: Percutaneous radiofrequency ablation (RFA) is a minimally invasive and curative local treatment for hepatocellular carcinoma (HCC). However, serious concerns remain regarding critical recurrences such as metastasis, dissemination, and/or seeding due to RFA. In August 2006, we introduced selective feeding artery ablation before tumor ablation to reduce the risk of critical recurrence by blocking tumor blood flow. The aim of the present study was to clarify whether feeding artery ablation before tumor ablation can reduce the risk of critical recurrence after RFA. METHODS: This study retrospectively analyzed 279 patients with primary, solitary, and hypervascular HCC ≤5 cm in diameter who were treated with RFA alone between April 2001 and August 2013. Critical recurrence was defined as intra- or extrahepatic metastasis, dissemination, or seeding that was difficult to treat radically. RESULTS: Of the 279 HCC patients, 157 patients were treated with conventional RFA alone, and 122 patients underwent RFA with prior feeding artery ablation. Although no significant differences were seen in the rates of local tumor progression-free survival, overall recurrence-free survival, or overall survival between a conventional RFA group and a prior feeding artery ablation group, significant differences were seen in rates of critical recurrence-free survival and cancer-specific survival (5-year, 69 vs 81%, P = 0.01 and 76 vs 88%, P = 0.03, respectively). On multivariate analysis, prior feeding artery ablation, tumor diameter, and alpha-fetoprotein were independent factors related to critical recurrence. CONCLUSIONS: Feeding artery ablation before tumor ablation may reduce the risk of critical recurrence.

Sofosbuvir plus ribavirin is tolerable and effective even in elderly patients 75-years-old and over.

BACKGROUND: Although clinical use of sofosbuvir plus ribavirin has been approved for patients infected with genotype 2 hepatitis C virus, patients ≥ 75-years-old have not been included in previous clinical trials. AIM: To evaluate the real-world safety and efficacy of sofosbuvir plus ribavirin for elderly patients (≥ 75-years-old) compared to nonelderly patients, we conducted a post-marketing prospective cohort study. METHODS: We treated 265 patients with genotype 2 hepatitis C virus using standard approved doses of sofosbuvir (400 mg/d) plus ribavirin adjusted by body weight, administered orally for 12 wk. RESULTS: Sustained virological response rates for the overall cohort, patients < 65-years-old, ≥ 65-years-old but < 75-years-old, and ≥ 75-years-old were 97% (258/265), 98% (93/95), 97% (84/87), and 98% (81/83), respectively (P = 0.842). Logistic regression analyses identified history of hepatocellular carcinoma treatment and alpha-fetoprotein as factors significantly associated with sustained virological response. Alpha-fetoprotein was the only independent factor identified. Sustained virological response rate was significantly lower for patients with hepatocellular carcinoma treatment (91%) than for patients without history of hepatocellular carcinoma treatment (98%, P = 0.004). One patient (0.4%) discontinued treatment due to drug-induced pneumonia. Dose reduction or interruption of ribavirin was required for 12.1% (32/265) of patients because of anemia, including 7.7% (14/182) of patients < 75-years-old and 21.7% (18/83) of patients ≥ 75-years-old (P = 0.002). CONCLUSION: Although ribavirin dose reduction or interruption was required with advanced age, sofosbuvir plus ribavirin appears tolerable and highly effective even in patients ≥ 75-years-old.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography in patients with small hepatocellular carcinoma treated by radiofrequency ablation.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) uptake in hepatocellular carcinoma (HCC) is significantly associated with early recurrence and survival after curative surgical resection. However, there are no reports regarding the relationship between 18F-FDG uptake and outcomes after radiofrequency ablation (RFA). A prospective cohort study was conducted to evaluate the prognostic value of 18F-FDG positron emission tomography (PET) in HCC patients after RFA. METHODS: A total of 121 consecutive patients with primary HCC (≤3 tumors, of diameter ≤ 3 cm) without vascular invasion on imaging were examined by 18F-FDG-PET computed tomography prior to RFA. An HCC with a component of 18F-FDG uptake visibly stronger than that of surrounding liver was defined as 18F-FDG-PET positive. RESULTS: The median follow-up period was 1267 days. There were 110 18F-FDG-PET negative and 11 positive tumors. The cumulative 1-year recurrence rates in the 18F-FDG negative and positive groups were 30 and 64% (P = 0.017), respectively, and cumulative 1-year metastatic recurrence rates were 6 and 36% (P < 0.001), respectively. The cumulative 5-year survival rates were 88 and 22% (P < 0.001), respectively. Multivariate analysis revealed 18F-FDG-PET positivity and tumor size as independent factors related to metastatic recurrence and survival after RFA. CONCLUSIONS: 18F-FDG-PET positivity was significantly associated with outcomes after RFA. RFA should not be readily selected as the first-line treatment for small HCC that includes a component of visually strong 18F-FDG uptake.

Combination with portosystemic shunt occlusion and antiviral therapy improves prognosis of decompensated cirrhosis.

BACKGROUND AND AIM: Portosystemic shunt occlusion using endovascular treatment can transiently improve liver function in patients with decompensated cirrhosis. In recent years, viral hepatitis can be easily controlled. The present study aimed to clarify the safety and efficacy of endovascular treatment in decompensated cirrhotic patients, and to elucidate whether viral treatment improves the prognosis after shunt occlusion. METHODS: Among 98 cirrhotic patients who received portosystemic shunt occlusion from January 2007 to June 2016, we retrospectively analyzed 61 decompensated cirrhotic patients. RESULTS: Forty-five patients had viral hepatitis. Recovery rates of liver function to Child A within 6 months in viral hepatitis, non-viral hepatitis, and overall were 78% (35/45), 81% (13/16), and 79% (48/61), respectively. Recovery rates according to baseline Child-Pugh score were as follows: score 7, 88% (15/17); score 8, 89% (24/27); score 9, 69% (9/13); and score ≥ 10, 0% (0/4). Three-year reprogression rates to decompensated cirrhosis for non-virus, non-sustained viral negativity (SVN), and SVN groups were 23 100, and 0%, respectively (P < 0.01). Three-year survival rates for those were 63, 62, and 91%, respectively (P < 0.01). Eight-year survival rate for SVN group was also 91%. Multivariate analysis revealed age, baseline ammonia level, baseline Child class, and SVN as independent contributors to survival. CONCLUSIONS: SVN in patients with viral hepatitis appears prerequisite to maintaining recovered liver function by shunt occlusion and to improving prognosis. Combination therapy with shunt occlusion and antiviral treatment should be considered as a first-line treatment for decompensated cirrhotic patients with viral hepatitis and large portosystemic shunt growth.

Endoscopic ultrasound-guided radiofrequency ablation of porcine liver.

PURPOSE: Animal studies of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) of the liver have rarely been reported. We assessed the effectiveness and safety of EUS-RFA in pigs. METHODS: We conducted four experiments using newly designed RFA electrodes. In the first experiment, we ablated excised liver using 19 G electrodes with active electrode tips with lengths of 1, 1.5, and 2 cm. The second experiment was performed with the same electrodes as those used in the first experiment, but with the electrodes inserted into the livers of live pigs under EUS. In the third experiment, we tested the electrodes for water permeability. In the fourth experiment, we performed EUS-RFA on live pigs, using 19 G electrodes in 7/12 pigs and 18 G electrodes in 5/12 pigs. Complications were evaluated after 7 days of survival. RESULTS: The newly designed RFA electrodes achieved ablation of the liver. In the first experiment, the maximal sizes of the ablation areas were 27, 26, 24, and 25 mm at 10, 20, 30, and 40 W, respectively, with the 2-cm electrode. In the second experiment, the maximal vertical sizes were 22, 23, 22, and 23 mm at 10, 20, 30, and 40 W, respectively, with the 2-cm electrode. In the third experiment, the 18 G electrode had better water permeability than the 19 G electrode. In the fourth experiment, all pigs survived. Complications occurred in 1/5 (18 G electrode) and 4/7 (19 G electrode) pigs. CONCLUSION: We performed EUS-RFA in pigs and concluded that it may be feasible to perform RFA of lesions near the stomach.

Impact of the Sensitivity to Empiric Antibiotics on Clinical Outcomes after Biliary Drainage for Acute Cholangitis.

Background/Aims: Empiric antibiotics are given in combination with biliary drainage for acute cholangitis but sometimes turn out to be insensitive to microorganisms in blood and bile. Clinical outcomes were compared according to sensitivity to microorganisms detected in blood and bile culture to evaluate the impact of sensitivity to empiric antibiotics in cholangitis. Methods: Consecutive patients who underwent biliary drainage for acute cholangitis were retrospectively studied. Clinical outcomes such as 30-day mortality, length of hospital stay and high care unit stay, organ dysfunction and duration of fever were compared in three groups: group A (sensitive to both blood and bile culture), group B (sensitive to blood culture alone) and group C (insensitive to both blood and bile culture). Results: Eighty episodes of cholangitis were classified according to sensitivity results: 42, 32 and six in groups A, B and C. Escherichia coli and Klebsiella were two major pathogens. There were no significant differences in 30-day mortality rate (7%, 0%, and 0%, p=0.244), length of hospital stay (28.5, 21.0, and 20.5 days, p=0.369), organ dysfunction rate (14%, 25%, and 17%, p=0.500), duration of fever (4.3, 3.2, and 3.5 days, p=0.921) and length of high care unit stay (1.4, 1.2, and 1.7 days, p=0.070) in groups A, B and C. Empiric antibiotics were changed in 11 episodes but clinical outcomes appeared to be non-inferior even in 31 episodes of cholangitis who were on inadequate antibiotics throughout the course. Conclusions: Sensitivity of empiric antibiotics was not associated with clinical outcomes in acute cholangitis.

Real-world safety and efficacy of sofosbuvir and ledipasvir for elderly patients.

BACKGROUND AND AIM: In September 2015, sofosbuvir and ledipasvir were approved for clinical use in Japan for patients infected with genotype 1 hepatitis C virus. We conducted a postmarketing prospective cohort study to elucidate the safety and efficacy of this therapy in a real-world setting. METHODS: We treated 509 patients using standard doses of sofosbuvir and ledipasvir for 12 weeks. As sustained virological response (SVR) in 2 patients could not be evaluated, 507 patients were finally analyzed. Patients with daclatasvir plus asunaprevir failure were excluded. RESULTS: Four patients (0.8%) discontinued treatment due to adverse events. SVR rates for the overall cohort, patients <65 years old, ≥65 and <75 years old, and ≥75 years old were 98% (495/507), 98% (161/163), 96% (179/186), and 98% (155/158), respectively. SVR rates among cirrhotic patients, patients with moderate chronic kidney disease (CKD), patients with a history of hepatocellular carcinoma (HCC) treatment, patients with protease inhibitor (PI) triple therapy failure, and patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) were 97% (228/235), 98% (117/119), 95% (95/100), 94% (46/49), and 92% (44/48), respectively. In the comparison of factors between patients with and without SVR, high body weight, discontinuation of therapy, and NS5A RASs were significantly associated with non-SVR. CONCLUSIONS: In this real-world setting, sofosbuvir and ledipasvir were a safe treatment even in patients ≥75 years old. When patients without pre-existing NS5A RASs and daclatasvir plus asunaprevir failure are selected, extremely high SVR rates can be achieved irrespective of age.

Contribution of Contrast-Enhanced Sonography With Perfluorobutane Microbubbles for Diagnosis of Recurrent Hepatocellular Carcinoma.

OBJECTIVES: The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use. METHODS: A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrast-enhanced sonography, lesion size, location, and abdominal wall thickness were independent factors. CONCLUSIONS: Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.

Kupffer Imaging by Contrast-Enhanced Sonography With Perfluorobutane Microbubbles Is Associated With Outcomes After Radiofrequency Ablation of Hepatocellular Carcinoma.

OBJECTIVES: An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA). METHODS: For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis. RESULTS: The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin- reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin-reactive α-fetoprotein level, and defect pattern were independent factors related to survival. CONCLUSIONS: The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.

The arterial tumor enhancement pattern on contrast-enhanced computed tomography is associated with primary cancer death after radiofrequency ablation for small hepatocellular carcinoma.

BACKGROUND/PURPOSE: Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC. METHODS: Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (≤3 cm in diameter and ≤3 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain. RESULTS: The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22% (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13% (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis. CONCLUSIONS: Arterial heterogeneous tumor enhancement on CECT is associated with critical recurrence and cancer death after RFA for small HCC.

Prediction of Sustained Virological Response to Telaprevir-Based Triple Therapy Using Viral Response within 2 Weeks.

The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.