Child-Pugh grade deterioration stratified by the etiology after transcatheter arterial chemoembolization as initial treatment for hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.

Coincidental items in the definition of metabolic dysfunction-associated fatty liver are useful in identifying patients having significant fibrosis with fatty liver.

AIM: We aimed to establish a method that will identify patients at a high risk for progressive phenotype of fatty liver. METHODS: Patients with fatty liver who underwent liver biopsy between July 2008 and November 2019 were included as cohort 1, and those who underwent abdominal ultrasound screening examination by general physicians between August 2020 and May 2022 served as cohort 2. According to the definition of metabolic dysfunction-associated fatty liver (MAFLD), the subjects were classified by body mass index of ≥23, diabetes mellitus, and coexistence of two or more metabolic risk items. The progressive phenotype of MAFLD is defined by significant fibrosis complicated with either nonalcoholic fatty liver disease activity score ≥4 (BpMAFLD) or steatosis grade ≥2 by ultrasound examination (UpMAFLD). RESULTS: One hundred sixty-eight patients and 233 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, the prevalence of BpMAFLD was 0% in patients without a complicating factor (n = 10), 13% in those with one complicating factor (n = 67), 32% in those with two (n = 73), and 44% in those with all three complicating factors (n = 36). A logistic regression analysis revealed that factors in the MAFLD definition were significantly associated with BpMAFLD. In cohort 2, a criterion of two or more positive MAFLD definitions was found to have a 97.4% negative predictive value for the diagnosis of UpMAFLD. CONCLUSION: Patients with two or more complicating factors in the MAFLD definition should have further evaluation for liver fibrosis.

Comparing the Safety and Efficacy of Microwave Ablation Using ThermosphereTM Technology versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

There is limited information regarding the oncological benefits of microwave ablation using ThermosphereTM technology for hepatocellular carcinoma. This study compared the overall survival and recurrence-free survival outcomes among patients with hepatocellular carcinoma after microwave ablation using ThermosphereTM technology and after radiofrequency ablation. Between December 2017 and August 2020, 410 patients with hepatocellular carcinoma (a single lesion that was ≤5 cm or ≤3 lesions that were ≤3 cm) underwent ablation at our institution. Propensity score matching identified 150 matched pairs of patients with well-balanced characteristics. The microwave ablation and radiofrequency ablation groups had similar overall survival rates at 1 year (99.3% vs. 98.2%) and at 2 years (88.4% vs. 87.5%) (p = 0.728), as well as similar recurrence-free survival rates at 1 year (81.1% vs. 76.2%) and at 2 years (60.5% vs. 62.1%) (p = 0.492). However, the microwave ablation group had a significantly lower mean number of total insertions (1.22 ± 0.49 vs. 1.59 ± 0.94; p < 0.0001). This retrospective study revealed no significant differences in the overall survival and recurrence-free survival outcomes after microwave ablation or radiofrequency ablation. However, we recommend microwave ablation for hepatocellular carcinoma tumors with a diameter of >2 cm based on the lower number of insertions.

Survival Benefit of Hepatic Arterial Infusion Chemotherapy over Sorafenib in the Treatment of Locally Progressed Hepatocellular Carcinoma.

BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, n = 644; sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; p < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.

Decreased Mean Kurtosis in the Putamen is a Diagnostic Feature of Minimal Hepatic Encephalopathy in Patients with Cirrhosis.

Objective To prevent the development of overt hepatic encephalopathy, the early intervention for minimal hepatic encephalopathy (MHE) based on an accurate diagnosis is essential. This study investigated whether or not magnetic resonance diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) could detect brain microstructure abnormalities in MHE. The aim was to confirm whether or not brain microstructure abnormalities detected by magnetic resonance (MR) imaging could be used for the diagnosis of MHE. Methods Thirty-two subjects were prospectively examined with a 3-T MR scanner. Tract-based spatial statistics and region of interest analyses of diffusion imaging were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values between patients with and without minimal hepatic encephalopathy. The diagnostic performance for the detection of MHE was assessed with a receiver operating characteristic analysis. Results Ten subjects were diagnosed with MHE by neuropsychological testing. After the exclusion of unsuitable subjects, we analyzed 9 subjects with MHE and 14 without MHE. The patients with MHE had a reduced MK in the widespread white matter. We also found significant decreases in the MK in the caudate nucleus, putamen, globus pallidus, and/or thalamus in the subjects with MHE. The MK in the putamen showed the best diagnostic performance for differentiating the subjects with MHE from those without MHE (cut-off value, 0.74; sensitivity, 0.89; specificity, 0.86). Conclusion DKI detects changes in the cerebral white matter and basal ganglia regions of patients with MHE more sensitively than DTI. The MK values in the putamen can be a useful marker for diagnosing MHE from cirrhotic patients without MHE.

Updating the neuropsychological test system in Japan for the elderly and in a modern touch screen tablet society by resetting the cut-off values.

AIM: Covert hepatic encephalopathy is frequently seen in cirrhotic patients. This condition can be diagnosed by a computerized neuropsychological test system (NPT); however, NPT has not been updated for approximately two decades in Japan. The aim of this study is to update the NPT to be more suitable for both the elderly and modern society by resetting of cut-off values. METHODS: We enrolled 367 healthy subjects aged between 40 and 79 years old between 2003 and 2010. The NPT consists of the following eight tests: number connection tests (NCT)-A and -B, a figure position test, a digit symbol test, a block design test, and reaction time tests (RTT)-A, -B, and -C. All subjects were classified into eight groups (5-year quartile ranges from 40 to 79 years old), and the cut-off value for each test was compared to the former cut-off value (NPT version 1). RESULTS: In all eight tests, most of the cut-off values were different from those in NPT version 1. The difference was minimal in RTT-A, RTT-B, and RTT-C. However, the difference was evident in the NCT-A, NCT-B, digit symbol test, and block design test. In particular, a 57.8-s decrease in the cut-off value was seen in the 65-69-year-old group for the NCT-B test (71.3 s vs. 129.1 s). CONCLUSIONS: We updated the NPT by covering subjects aged 40-79 years and resetting the cut-off values. Thus, the updated NPT is an elderly and modern subject-compliant application. This update may improve the diagnostic ability of covert hepatic encephalopathy in contemporary cirrhotic patients.

Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic resonance spectroscopy.

AIM: To examine whether the brain exhibits metabolic disorder prior to overt hepatic encephalopathy in patients with liver cirrhosis (LC), the intracerebral glutamine and myo-inositol levels were determined using 3.0-Tesla (T)(1) H (proton) magnetic resonance spectroscopy (MRS). METHODS: We tested 21 LC patients, including seven patients with minimal hepatic encephalopathy (MHE). RESULTS: No significant differences were noted between the two patient groups in terms of the severity of LC, levels of blood ammonia or levels of blood or liver enzymes. In the MHE group, the levels of brain glutamine were significantly higher than those in the non-MHE group, whereas the levels of brain myo-inositol were significantly lower. This demonstrated that MHE patients were already exhibiting metabolic disorder in the brain, similar to those observed during overt hepatic encephalopathy. CONCLUSION: A quantitative analysis of this phenomenon using MRS may contribute to an early and objective diagnosis of MHE.

Bimodal peaks of liver stiffness in a case of drug-induced liver injury.

A 69-year-old male complained of general fatigue and presented with elevation of liver enzymes without any cause of liver injury. We diagnosed him with hepatocellular drug-induced liver injury (DILI). Liver stiffness, which was evaluated according to the shear wave velocity (SWV) using virtual touch tissue quantification, was serially observed during hospitalization. A fast SWV was noted on the date of admission, indicating a "hard" degree of liver stiffness. The SWV gradually decreased until the 20th hospital day. However, the patient's liver enzymes again became elevated on the 20th hospital day, and the SWV simultaneously increased in association with a rise in the total bilirubin level. The laboratory data for the second peak of the SWV indicated mixed-type DILI; therefore, the patient's pathological state transitioned from the hepatocellular type to the mixed type. A liver biopsy performed before discharge revealed a state of recovery from acute inflammation without fibrotic changes. We conclude that the second peak of the SWV may be affected by the presence of intrahepatic cholestasis. We herein report the occurrence of bimodal peaks of liver stiffness in a patient with DILI. In such cases, each peak of liver stiffness may be the result of a different pathological mechanism, namely acute inflammation versus acute intrahepatic cholestasis. Although the detailed mechanisms underlying the development of liver stiffness due to intrahepatic cholestasis remain unclear, this case presented a limitation of virtual touch tissue quantification for evaluation of liver stiffness as fibrosis marker in the liver with intrahepatic cholestasis.

Efficacy of hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic pegylated interferon α-2b for advanced intrahepatic cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). The prognosis of ICC is far worse than that of ECC. In this pilot trial, the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) combined with subcutaneous administration of pegylated interferon (PEG-IFN) α-2b in patients with advanced ICC was evaluated. METHODS: The subjects were 20 advanced ICC patients treated using subcutaneous PEG-IFNα-2b (50-100 µg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥1 cycle. RESULTS: The objective early response rate was 60.0 %. Cumulative survival rates were 71.6 % at 6 months, 53.7 % at 12 months, 28.6 % at 18 months, and 14.3 % at 24 months. Median survival time was 14.6 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. CONCLUSIONS: The combination therapy of PEG-IFNα-2b and 5-FU for advanced ICC seems not to be worse than the results of the previous studies. Furthermore, most adverse effects are transient and well tolerated. Based on the present findings, this combination therapy may be useful for patients with advanced ICC as one of the therapeutic option.