A successful case of transarterial chemoembolization for hyperprogressive disease induced by immunotherapy in a patient with unresectable hepatocellular carcinoma.

A fraction of patients with hepatocellular carcinoma (HCC) shows unexpected rapid tumor growth, called hyperprogressive disease (HPD) after the initiation of atezolizumab and bevacizumab (ATZ + BEV). However, little information is available concerning salvage therapy after HPD and the possibility of resuming ATZ + BEV. A 60-year-old woman with unresectable HCCs was treated with transarterial chemoembolization (TACE) and followed by lenvatinib, which showed an unsatisfactory result. Multiple HCCs had been noted in both lobes just before ATZ + BEV treatment. After the initiation of ATZ + BEV, a tumor in the left lobe grew rapidly. The tumor growth kinetics ratio and tumor growth rate ratio of the rapidly growing lesion were 3.76 and 2.02, respectively. Thyroid dysfunction was noted after the initiation of ATZ + BEV. The neutrophil/lymphocyte ratios just before and at 3 weeks after the first ATZ + BEV treatment were 3.89 and 3.5, respectively. Drug-eluting bead (DEB)-TACE using cisplatin was performed for the rapidly growing tumor, which was effective for the targeted HCC in the left lobe as well as multiple HCCs in the right lobe. We were able to resume and continue ATZ + BEV without HPD, which was effective for HCC. We considered that DEB-TACE is an option for treating HPD.

Utility of FibroScan-based scoring systems to narrow the risk group of nonalcoholic fatty liver disease with comorbidities.

BACKGROUND: Vibration-controlled transient elastography (VCTE) is proposed as a second step of examination to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) after triaging by the fibrosis-4 (FIB-4) index. Recently, VCTE-based scoring systems, including FibroScan-AST (FAST), Agile 3+, and Agile 4, emerged to determine the status of NAFLD. However, the significance of these scoring systems remains unknown in narrowing the high-risk group of NAFLD patients with comorbidities, including hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). AIM: To clarify the significance of VCTE-based scoring systems to narrow the high-risk group of NAFLD patients with comorbidities. METHODS: We performed a cross-sectional study to investigate the usefulness of VCTE-based scoring systems and other fibrosis markers to narrow the high-risk group of patients with NAFLD. FIB-4 index was used for the first triage. Risk groups of FAST, Agile 3+, and Agile 4 were stratified according to the published data. Among the 191 patients with NAFLD, there were 26 (14%) and 25 patients (13%) with HCC and EGV, respectively. RESULTS: When 1.3 was used as a cutoff value, the FIB-4 index narrowed the risk group to 120 patients, in which all patients with HCC and/or EGV were included. High risk group of Agile 3+ could subsequently narrow the risk group. The prevalence of HCC and EGV at this step were 33% (26/80) and 31% (25/80), respectively. In further narrowing of EGV, Agile 4 aggregated the patients with EGV into 43 patients, of whom 23 (53%) had EGV. FAST failed to narrow the risk group of patients with comorbidities. When 2.6 was used as a cutoff value of the FIB-4 index, three patients with HCC and two patients with EGV were missed at the first triage. CONCLUSION: Agile 3+ and Agile 4 are useful to narrow the NAFLD patient group, in which patients may have HCC and/or EGV.

Conventional Therapies Do Not Prolong the Prognosis of Hepatocellular Carcinoma Patients with Extrahepatic Metastases under Receiving of Tyrosine Kinase Inhibitors.

BACKGROUND: Conventional therapies, including chemoembolization and radiation therapy, have been expected to prolong the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases, which remains poor. However, little information is available on the efficacy of conventional therapies for such patients under tyrosine kinase inhibitor (TKI) treatment. METHODS: We retrospectively investigated 127 HCC patients with extrahepatic metastases, who were divided into the non-TKI (conventional therapies) and TKI groups and further subdivided into the TKI alone and TKI plus conventional therapies groups. Conventional therapies included transcatheter arterial chemoembolization, cisplatin-based chemotherapy, radiation, surgery, and UFT, an oral chemotherapeutic agent. RESULTS: The median of the overall survival (OS) of the 127 patients with extrahepatic metastases was 7.0 months. Meanwhile, the median OS of the TKI and non-TKI groups was 12.1 and 4.1 months, respectively. Imitating TKI after diagnosing metastases promoted a favorable increase in OS. Among the TKI group, the median OS in the TKI alone group was 8.9 months. TKI plus conventional therapies promoted no improvement in OS after adjusting for the patients' background data. CONCLUSION: TKI promoted a better OS in HCC patients with extrahepatic metastases compared to conventional therapies. However, TKI plus conventional therapies promoted no improvement in the prognosis of such patients.

Oxidized High-Density Lipoprotein Shows a Stepwise Increase as Fibrosis Progresses in Patients with Nonalcoholic Fatty Liver Disease.

Patients with nonalcoholic fatty liver disease (NAFLD) show dyslipidemia and a high risk for coronary heart disease (CHD). However, conventional atherosclerotic lipids are found at low levels in NAFLD patients with advanced fibrosis, in whom the risk for CHD is extremely high. The aim of the present study was to evaluate the levels of oxidized high-density lipoprotein (oxHDL), an emerging atherosclerotic biomarker, in patients with NAFLD. A total of 32 non-NAFLD subjects and 106 patients with NAFLD were enrolled. The fibrosis grades were stratified using non-invasive methods, including the Fibrosis-4 index and NAFLD fibrosis score. Total cholesterol and low-density lipoprotein (LDL)-cholesterol levels were significantly low in patients with advanced liver fibrosis. In contrast, oxHDL levels were high in NAFLD patients and showed a stepwise increase as fibrosis progressed. These oxHDL levels were independent of the HDL cholesterol levels, and statin use did not influence the oxHDL levels. Obese patients showed no increase in oxHDL levels, whereas patients with a low handgrip strength showed high oxHDL levels in NAFLD with advanced fibrosis. In conclusion, oxHDL is a potential biomarker for assessing the status of patients with NAFLD, including CHD and metabolic/nutritional disturbance, and particular cases with advanced liver fibrosis.

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection.

Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in "rural" regions. Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.

Successful treatment of hepatocellular carcinoma by laparoscopic radiofrequency ablation in a patient with hemophilia A.

Percutaneous radiofrequency ablation (RFA) is a good indication for hepatocellular carcinoma (HCC) in cases involving ≦ 3 tumors of ≦ 30 mm in size, many hepatologists are hesitant to perform the procedure for patients with hemorrhagic disorders. We herein report the successful treatment of HCC by laparoscopic RFA in a patient with hemophilia A. A 48-year-old man with moderate form of hemophilia A had a single HCC at segment 8. To perform laparoscopic RFA safely, recombinant factor VIII (rFVIII) was administered to maintain factor VIII activity (FVIII:C) > 80% on the operation day and > 40% for 6 days after the operation in accordance with the guidelines. A total of 23,000 units of rFVIII was used. Laparoscopic RFA was completed with an operation time of 105 min and < 10 mL of blood loss. As a result, blood transfusion was not required. At 2 years after the initial treatment, HCC recurred at segment 7. Under rFVIII supplementation, we performed a second laparoscopic RFA without any events. Although partial hepatectomy is the main procedure used to treat HCC in patients with hemophilia, we could reduce in total use of rFVIII, blood and operation time by laparoscopic RFA compared with those in partial hepatectomy.

Acute Liver Failure Caused by the Transmission of Hepatitis B Virus from the Spouse after 38 Years of Marriage.

A 65-year-old man presented with acute liver failure and grade IV coma caused by hepatitis B virus (HBV) infection in 2017. The patient died on day 12 from the disease onset. The HBV isolated from the patient was genotype/subgenotype B/B1 and had multiple genomic mutations. The patient's wife was hepatitis B surface antigen (HBsAg)-positive when she delivered her first daughter in 1979. The HBV isolates of the patient and the wife shared 100% similarity over the entire genome. Because the patient's HBsAg value had been negative one year earlier, we considered the source of HBV transmission to be his wife.

Usefulness of Gd-EOB-DTPA-enhanced MRI for evaluating the potential for early development of hepatocellular carcinoma after HCV eradication by direct-acting antiviral treatment.

Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment. Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients' characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed. Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001). Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.