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This study aimed to determine the relationship between animal naming test (ANT), falls, and fall-related fractures in patients with cirrhosis. Cognitive impairment and frailty were assessed using ANT and Karnofsky performance status (KPS), respectively. Factors stratifying the risk of previous falls and fall-related fractures within 1 year were assessed using a logistic regression model. Factors affecting patient performance in ANT were evaluated using multiple regression analysis. Of the 94 patients, 19% and 5% experienced falls and fall-related fractures, respectively. The performance in ANT was worse in patients who experienced falls (11 vs. 18; p < 0.001) and fall-related fractures (8 vs. 16; p < 0.001) than in those who did not. After adjustment, females, KPS, and ANT (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.65–0.93; p = 0.005) were associated with falls, while ANT was significantly associated with fall-related fractures (OR, 0.56; 95% CI 0.35–0.88; p = 0.012). Age and education affected the performance in ANT, whereas the use of Oriental zodiac did not. The ANT is useful for stratifying the risk of falls and fall-related fractures in patients with cirrhosis. The effects of age and education should be considered when applying ANT in the Japanese population. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is a serious condition with high mortality and a high permanent disability rate. In this study, we examined the association of clinical outcome with the Controlling Nutritional Status (CONUT) score during hospitalization in aSAH patients. A single-center, retrospective observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for aSAH and diagnosed with World Federation of Neurosurgical Societies (WFNS) grade III and IV aSAH between April 2004 and March 2021 were enrolled. A logistic regression model was constructed to evaluate the association of the CONUT score with a modified Rankin scale (mRS) ≥ 3 and delayed cerebral ischemia (DCI). 127 patients diagnosed with WFNS grade III and IV aSAH were analyzed. CONUT score was significantly associated with mRS ≥ 3 during hospitalization. The score obtained by subtracting the CONUT score at admission from the maximum CONUT score was significantly associated with mRS ≥ 3 at discharge. Moreover, the score obtained by subtracting the CONUT score at admission from the maximum CONUT score during the first 14 days was significantly associated with DCI within 14 days from admission. These findings indicate that CONUT score during hospitalization may be a useful daily marker for predicting poor outcomes in aSAH patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the impact of body composition on the risk of portopulmonary hypertension using computed tomography (CT) in patients with liver cirrhosis. We retrospectively included 148 patients with cirrhosis treated at our hospital between March 2012 and December 2020. POPH high-risk was defined as main pulmonary artery diameter (mPA-D) ≥ 29 mm or mPA-D to ascending aorta diameter ratio ≥ 1.0, based on chest CT. Body composition was assessed using CT images of the third lumbar vertebra. The factors associated with POPH high-risk were evaluated using logistic regression and decision tree analyses, respectively. Among the 148 patients, 50% were females, and 31% were found to be high-risk cases on evaluation of chest CT images. Patients with a body mass index (BMI) of ≥25 mg/m2 had a significantly higher prevalence of POPH high-risk than those with a BMI < 25 mg/m2 (47% vs. 25%, p = 0.019). After adjusting for confounding factors, BMI (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.10–1.33), subcutaneous adipose tissue index (OR, 1.02; 95% CI, 1.01–1.03), and visceral adipose tissue index (OR, 1.03; 95% CI, 1.01–1.04) were associated with POPH high-risk, respectively. In the decision tree analysis, the strongest classifier of POPH high-risk was BMI, followed by the skeletal muscle index. Body composition may affect the risk of POPH based on chest CT assessment in patients with cirrhosis. Since the present study lacked data on right heart catheterization, further studies are required to confirm the results of our study. [ABSTRACT FROM AUTHOR]

Selenium is an essential trace element to maintain good health. This retrospective study investigated the prevalence of selenium deficiency and its effect on overt hepatic encephalopathy (OHE) in patients with chronic liver disease (CLD). Patients who underwent serum selenium level measurement between January 2021 and April 2022 were enrolled. The factors associated with selenium deficiency (≤10 µg/dL) and the association between selenium deficiency and OHE were analyzed. Among 98 eligible patients, 24% were observed to have selenium deficiency, with a median serum selenium level of 11.8 µg/dL. The serum selenium levels were significantly lower in patients with cirrhosis than in those with chronic hepatitis (10.9 µg/dL vs. 12.4 µg/dL; p = 0.03). The serum selenium levels were negatively correlated with mac-2 binding protein glycan isomer, the FIB-4 index, albumin-bilirubin (ALBI) score, and Child–Pugh score. The ALBI score remained significantly associated with selenium deficiency (odds ratio, 3.23; 95% confidence interval [CI], 1.56–6.67). During a median follow-up period of 2.9 months, nine patients experienced OHE. Selenium deficiency was associated with OHE (hazard ratio, 12.75; 95% CI, 2.54–70.22). Selenium deficiency is highly prevalent in patients with CLD and is associated with an increased risk of OHE development. [ABSTRACT FROM AUTHOR]

Circulating albumin structures, including their oxidized and reduced forms, are involved in hepatic encephalopathy (HE) development. However, the effects of rifaximin, a key drug in HE treatment, on the circulating albumin structure in patients with liver cirrhosis remain unclear. In this multicenter prospective study, eight patients with hyperammonemia (≥80 μg/dL) were enrolled. The circulating albumin structure was evaluated using the ratio of oxidized albumin (human nonmercaptalbumin, HNA). Patients were administered 400 mg rifaximin 3 times/day for 3 months, and laboratory data were assessed at baseline and during observation. Among the eight patients, three were men; the median age and body mass index were 70 years and 26.4 kg/m2, respectively. The median HNA and serum ammonia levels at baseline were 41% and 143 μg/dL, respectively. After rifaximin therapy, HNA showed a decreasing tendency (median; from 41% to 36%, p = 0.321), but serum albumin levels showed no significant change (from 3.5 g/dL to 3.5 g/dL, p = 1.00); serum ammonia levels significantly reduced (median: 143 μg/dL to 76 μg/dL, p = 0.015). Thus, rifaximin reduces serum ammonia levels and may improve circulating albumin structure in patients with cirrhosis. Further large-scale studies are required to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Aim: Covert hepatic encephalopathy (CHE) adversely affects clinical outcomes in patients with liver cirrhosis, although its diagnosis is difficult. This study aimed to establish a simple CHE screening model based on blood-related biochemical parameters. Methods: This retrospective study enrolled 439 patients who were assessed for CHE using a neuropsychiatric test between January 2011 and June 2019. A simple CHE (sCHE) score was calculated with hypoalbuminemia (≤ 3.5 g/dL) and hyperammonemia (≥ 80 μg/dL) as 1 point each. The association between sCHE score and CHE or overt hepatic encephalopathy (OHE) was assessed using logistic regression and Fine-Gray competing risk regression models. Results: Of 381 eligible patients, 79 (21%) were diagnosed with CHE. The distribution of sCHE scores was 48% with 0 point, 33% with 1 point, and 19% with 2 points. Patients with sCHE score ≥ 1 point had a higher prevalence of CHE than those with sCHE score of 0 (27% vs. 14%, P = 0.002). A cut-off value of 1 point showed high discriminative ability for identifying CHE, with a sensitivity of 0.67, specificity of 0.56, positive predictive value of 0.27, and negative predictive value of 0.86. During the median follow-up period of 2.2 years, 58 (15%) patients developed OHE. Multivariate analysis showed that sCHE score ≥ 1 (sub-distribution hazard ratio [SHR], 2.69; 95% confidence interval [CI], 1.41–5.15) and CHE (SHR, 2.17; 95% CI, 1.26–3.73) independently predicted OHE. Conclusions: The sCHE score is a useful screening model for identifying patients with CHE and for predicting OHE occurrence. [ABSTRACT FROM AUTHOR]

The trabecular bone score (TBS), a surrogate measure of bone microarchitecture, provides complementary information to bone mineral density (BMD) in the assessment of osteoporotic fracture risk. This cross-sectional study aimed to determine whether TBS can identify patients with liver cirrhosis that are at risk of vertebral fractures. We enrolled 275 patients who completed evaluations for lumbar BMD, TBS, and vertebral fractures between November 2018 and April 2021. BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was calculated by analyzing DXA images using TBS iNsight software, and vertebral fractures were evaluated using Genant's semi-quantitative method with lateral X-ray images. Factors associated with vertebral fractures and their correlation with the TBS were identified using regression models. Of the enrolled patients, 128 (47%) were female, the mean age was 72 years, and 62 (23%) were diagnosed with vertebral fractures. The prevalence of vertebral fractures was higher in women than in men (33% vs. 14%; p < 0.001). The unadjusted odds ratio (OR) of the vertebral fractures for one standard deviation decrease in TBS and BMD was 2.14 (95% confidence interval [CI], 1.69–2.73) and 1.55 (95% CI, 1.26–1.90), respectively. After adjusting for age, sex, and BMD, the adjusted OR of the vertebral fractures in TBS was 2.26 (95% CI, 1.52–3.35). Multivariate linear regression analysis showed that TBS was independently correlated with age (β = −0.211), body mass index (β = −0.251), and BMD (β = 0.583). TBS can help identify patients with cirrhosis at risk of vertebral fractures. [ABSTRACT FROM AUTHOR]

Diagnosing sarcopenia is challenging. This multicenter cross-sectional study aimed to evaluate the utility of the SARC-F score system for identifying sarcopenia in patients with chronic liver disease (CLD). We enrolled 717 patients from five participating centers who completed the SARC-F between November 2019 and March 2021. Sarcopenia was diagnosed based on the Japan Society of Hepatology Working Group on Sarcopenia in Liver Disease Consensus. Muscle strength was estimated using a grip dynamometer, and muscle mass was assessed using computed tomography or bioelectrical impedance analysis. The association between SARC-F and sarcopenia was analyzed using a logistic regression model. The optimal SARC-F cutoff value for identifying sarcopenia was determined using receiver operating characteristic (ROC) curve analysis. Of the 676 eligible patients, 15% were diagnosed with sarcopenia. The SARC-F distribution was 0 points in 63% of patients, 1 point in 17%, 2 points in 7%, 3 points in 4%, and ≥4 points in 8%. The SARC-F items of "Strength" (odds ratio (OR), 1.98; 95% confidence interval (CI), 1.03–3.80) and "Falls" (OR, 2.44; 95% CI, 1.48–4.03) were significantly associated with sarcopenia. The SARC-F value of 1 point showed a higher discriminative ability for identifying sarcopenia than the 4 points that are conventionally used (p < 0.001), with an area under the ROC curve of 0.68, sensitivity of 0.65, specificity of 0.68, positive predictive value of 0.27, and negative predictive value of 0.92. SARC-F is useful for identifying patients with CLD who are at risk of sarcopenia. [ABSTRACT FROM AUTHOR]

The clinical efficacy of a late evening snack (LES) is well documented in patients with cirrhosis, but its effect on survival remains unclear. This cohort study aimed to compare the overall survival between LES-treated patients and untreated patients. We conducted a retrospective cohort study to determine the effect of LES, which is defined as an oral intake of a branched-chain amino acids (BCAA)-enriched nutrient before bedtime, on survival in 523 patients with cirrhosis seen at a tertiary referral center in Japan from March 2004 to April 2019. The association between LES and all-cause mortality was evaluated using propensity score matching and inverse probability of treatment weighting analyses. The median age of the 523 participants was 66 years; 286 (55%) patients were men and 87 (17%) received LES therapy. Of the 231 propensity-matched patients, 20 (26%) LES-treated patients and 72 (47%) untreated patients died during a median follow-up of 2.0 years (interquartile range, 0.5–4.8). Propensity score matching analysis showed that the overall survival was significantly higher in LES-treated patients than in untreated patients (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34–0.93). The survival benefit of LES therapy was most prominent in patients with Child–Pugh C cirrhosis (HR, 0.40; 95% CI, 0.20–0.81). Inverse probability of treatment weighting analysis also revealed that LES significantly improved the prognosis of patients with cirrhosis (HR, 0.57; 95% CI, 0.33–0.99). In this retrospective study of patients with cirrhosis, we found that nocturnal BCAA supplementation was associated with a significant reduction in the risk of death in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

This cross-sectional study examined the prevalence and characteristics of steatotic liver disease (SLD) based on a recently introduced nomenclature in the Japanese health checkup population. SLD was evaluated using liver ultrasonography, and participants were categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol associated steatotic liver disease (MetALD), alcohol-associated/related liver disease (ALD), and cryptogenic SLD groups. The prevalence and characteristics of the SLD subclasses were assessed, and subgroup analyses were conducted for the non-obese (body mass index [BMI] ≤ 25 kg/m2) and lean (BMI ≤ 23 kg/m2) populations. Among the 694 participants, with a median age of 47 years and comprising 54% males, the prevalence of MASLD, MetALD, ALD, and cryptogenic SLD was 26%, 2%, 1%, and 2%, respectively. A remarkable difference was observed in the prevalence of SLD subclasses according to age, sex, and BMI. Subgroup analyses revealed heterogeneous demographic, clinical, and biochemical parameters between the SLD categories. Individuals with MetALD had higher gamma-glutamyl transferase levels, lower platelet counts, and higher fibrosis-4 index than did those with MASLD. Furthermore, the prevalence of non-obese and lean MASLD was 13% and 6%, respectively. This study provides preliminary information on the prevalence of SLD based on a new nomenclature in the Japanese population. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia, the loss of skeletal muscle mass and strength, is associated with poor clinical outcomes in patients with hepatocellular carcinoma (HCC). This study indicated that lenvatinib treatment significantly exacerbated the decrease in skeletal muscle mass, whereas atezolizumab plus bevacizumab (AB) treatment did not. Furthermore, skeletal muscle mass was found to be an independent predictor of survival, together with alpha-fetoprotein and albumin-bilirubin scores, using time-varying covariates in the Cox proportional hazards model. These findings suggest that maintaining a relatively high skeletal muscle mass during AB treatment is advantageous for improving the prognosis of HCC chemotherapy. This study aimed to evaluate chronological changes in skeletal muscle index (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI), AFP, PIVKA-II, and ALBI scores during atezolizumab plus bevacizumab (AB) or lenvatinib (LEN) treatment for hepatocellular carcinoma (HCC) and the effect of these changes on survival. A total of 94 patients with HCC (37 were on AB and 57 on LEN) were enrolled. SMI, SATI, VATI, AFP, PIVKA-II, and ALBI scores were analyzed at the time of the treatment introduction (Intro), 3 months after the introduction (3M), at drug discontinuation (End), and the last observational time (Last). The differences between chronological changes were analyzed using the Wilcoxon paired test. The independent predictors for survival and the changes in SMI during AB or LEN (c-SMI%) were analyzed using the Cox proportional hazards model treating all these factors as time-varying covariates and the analysis of covariance, respectively. SMI in the AB group was maintained over time (42.9–44.0–40.6–44.2 cm2/m2), whereas that in the LEN group significantly decreased during the Intro–3M (p < 0.05) and 3M–End (p < 0.05) period (46.5–45.1–42.8–42.1 cm2/m2). SMI (p < 0.001) was an independent predictor for survival together with AFP (p = 0.004) and ALBI score (p < 0.001). Drug choice (AB or LEN; p = 0.038) and PIVKA-II (p < 0.001) were extracted as independent predictors for c-SMI%. AB treatment was significantly superior to LEN in terms of maintaining skeletal muscle, which is an independent predictor for survival. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the suppressive effect of direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) recurrence following curative treatment, particularly compared with interferon (IFN)-based therapy. Among 117 curative cases of HCV-related initial HCC between 2006 and 2017 at Gifu University Hospital, 13 and 14 cases achieved a sustained virological response (SVR) by DAA- (DAA group) or IFN-based therapies (IFN group), and 64 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative treatment in each group was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards model was used to analyze the factors that affected RFS. Age was significantly lower and serum alanine aminotransferase level was significantly higher in the IFN group than in both the DAA and non-treatment groups. There was a significant difference in RFS between the non-treatment group and antiviral therapy groups, including the DAA (P=0.014) and IFN groups (P=0.009); however, no significant difference was identified in RFS between the DAA and IFN groups (P=0.564). SVR achieved by DAA [P=0.011; hazard ratio (HR), 0.222; 95% CI, 0.069-0.758] or IFN therapy (P=0.007; HR, 0.327; 95% CI, 0.145-0.742) was an independent factor for the prevention of HCC recurrence. SVR by DAA therapy exhibited an anti-liver tumorigenesis effect equal to that of IFN-based therapy and reduced the risk of HCC recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: Skeletal muscle depletion is one of the established prognostic factors for hepatocellular carcinoma (HCC). This study clearly demonstrated that skeletal muscle mass continued to decrease significantly during lenvatinib (LEN) or sorafenib (SOR) treatment, which has recently played a major role in the treatment of unresectable HCC. Furthermore, the survival analysis using time-varying covariates in this study revealed that it was one of the independent prognostic factors together with tumor makers and liver functional reserve. These results can help improve the management of unresectable HCC because they suggest that it is essential to prevent skeletal muscle depletion, especially in using LEN/SOR to improve survival in HCC patients. This study aimed to assess the effects of lenvatinib (LEN) or sorafenib (SOR) treatment for hepatocellular carcinoma (HCC) on body composition and changes in body composition on survival. This study enrolled 77 HCC patients. Skeletal muscle index (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI), AFP, PIVKA-II, and ALBI scores were analyzed at the time of LEN/SOR introduction, three months after the introduction, at treatment discontinuation, and the last observational time. The differences between chronological changes in these values were analyzed using a paired t-test. The Cox proportional hazards model was used to analyze prognostic factors using time-varying covariates. The chronological changes in each factor were 45.5–43.6–40.6–39.8 (cm2/m2) for SMI, 41.7–41.6–36.3–33.7 (cm2/m2) for SATI, 41.9–41.1–37.1–34.8 (cm2/m2) for VATI, 2.379–26.42–33.61–36.32 (×103 ng/mL) for AFP, 9.404–13.39–61.34–25.70 (×103 mAU/mL) for PIVKA-II, and −2.56–−2.38–−1.99–−1.90 for the ALBI score. The presence of pre-treatment (p = 0.042), AFP (p = 0.002), PIVKA-II (p < 0.001), ALBI score (p < 0.001), and SMI (p = 0.001) were independent prognostic factors. Skeletal muscle mass decreases significantly during LEN/SOR treatment and is an independent prognostic factor for HCC. [ABSTRACT FROM AUTHOR]

We aimed to assess metabolic dysfunction-associated fatty liver disease (MAFLD) and alcohol-related liver disease (ALD) prevalence in young male adults and the role of health checkups in disease screening. We recruited 313 male graduate students at Gifu University in April 2022. With hepatic steatosis diagnosed by ultrasonography, MAFLD and nonalcoholic fatty liver disease (NAFLD) were diagnosed based on health checkup data, and ALD was diagnosed with alcohol consumption > 30 g/day. The ability of each variable to identify MAFLD, NAFLD, and ALD was assessed using logistic regression and receiver-operating characteristic curve analyses. Participants' mean age was 23 (± 4) years, and MAFLD, NAFLD, and ALD prevalence was 11%, 17%, and 1%, respectively. Among Japanese male young adults, alanine aminotransferase (ALT) (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.07; P = 0.008) and body mass index (BMI) (OR 2.02; 95% CI 1.58–2.58; P < 0.001) were independently associated with MAFLD. Furthermore, only the alcohol use disorders identification test (AUDIT) was able to identify ALD (OR 1.49; 95% CI, 1.28–1.74; P = 0.001). Our study revealed that health checkups, including measurement of ALT, BMI, and AUDIT, are important for screening MAFLD and ALD in younger generations. [ABSTRACT FROM AUTHOR]

Simple Summary: Atezolizumab plus bevacizumab (Atez/Bev) treatment is now recommended as a first-line systemic treatment for unresectable hepatocellular carcinoma. In this study, we evaluated the therapeutic effects and adverse events of Atez/Bev treatment in the real world including patients with Child–Pugh B or non-viral hepatitis and those who received Atez/Bev treatment as a later-line treatment. Furthermore, we analyzed the factors affecting the overall survival among changes in the clinical indicators representing liver function and tumor-related factors within 3 months after the introduction of Atez/Bev treatment. The results of this study may be useful in determining whether to continue or modify Atez/Bev treatment at an early stage after starting this treatment. In this study, we aimed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) treatment for unresectable hepatocellular carcinoma (HCC) and to analyze the factors affecting overall survival (OS). A total of 69 patients who received Atez/Bev at our institutions for unresectable HCC were enrolled in this study. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Changes in clinical indicators within 3 months were defined as delta (∆) values, and the Cox proportional hazards model was used to identify which ∆ values affected OS. The median OS, PFS, objective response rate, and disease control rate were 12.5 months, 5.4 months, 23.8%, and 71.4%, respectively. During the observational period, 62 patients (92.5%) experienced AEs (hypertension (33.3%) and general fatigue), and 27 patients (47.4%) experienced grade ≥ 3 AEs (hypertension (10.1%) and anemia (7.2%)). There was a significant deterioration in the albumin-bilirubin (ALBI) score (−2.22 to −1.97; p < 0.001), and a reduction in PIVKA-II levels (32,458 to 11,584 mAU/mL; p = 0.040) within 3 months after commencing Atez/Bev. Both the worsening ∆ ALBI score (p = 0.005) and increasing ∆ PIVKA-II (p = 0.049) were significantly associated with the OS of patients. [ABSTRACT FROM AUTHOR]

This study evaluated the factors that affect the recurrence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients, who had received curative treatment for initial HCC, using decision tree analysis in 111 curative cases. The enrolled patients were divided into three groups by the decision tree analysis as follows: Patients who achieved sustained virological response (SVR) after curative treatment belonged to Group 1 (n = 33), those who did not achieve SVR and with alpha-fetoprotein (AFP) levels < 11 ng/mL belonged to Group 2 (n = 30), and those who did not achieve SVR and with AFP levels ≥ 11 ng/mL belonged to Group 3 (n = 48). The Kaplan–Meier method revealed that Group 1 had significantly longer recurrence-free survival than Group 2 or 3 (p = 0.004). Moreover, there was no significant difference between patients achieving SVR with direct-acting antivirals and interferon therapy (p = 0.251). Group 3 had significantly poorer recurrence-free survival than Group 2 (p < 0.001). The Cox proportional hazards model demonstrated that SVR achievement was the only independent factor associated with low HCC recurrence (p = 0.005). In conclusion, patients who achieved SVR were the least prone to HCC recurrence, whereas those who did not achieve SVR and had AFP levels ≥ 11 ng/mL were the most prone to HCC recurrence. [ABSTRACT FROM AUTHOR]

Non-viral hepatocellular carcinoma (HCC) tends to appear in non-cirrhotic livers, rendering it difficult to screen for a high-risk group. The present study aimed to identify the most suitable indicator for screening high-risk groups of non-viral HCC. A total of 190 patients with non-viral HCC, including 126 with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), were enrolled in the present study. A total of two cut-off values, for low and high levels of fibrosis, were set for each of the indicators, including the Child-Pugh score (CPS; 6 and 7), platelet counts (15.8 and 10x104/µl), albumin-bilirubin (ALBI) score (-2.60 and -2.27), fibrosis 4 index (FIB-4 index; 1.30 and 2.67) and NAFLD fibrosis score (NFS; -1.455 and 0.675). The ratio of the number of patients who fell outside the cut-off value for all patients was defined as the overlooking rate. The overlooking rates of CPS, platelet counts, ALBI score, FIB-4 index and NFS for the low fibrosis cut-off value were 41.0, 48.9, 35.8, 4.2 and 5.8%, respectively. When performing analysis limited to the NAFLD cases, those of the FIB-4 index and NFS were 4.8 and 6.3%, respectively. Those for the high fibrosis cut-off value were 79.5, 73.2, 62.6, 30.0 and 37.4%, respectively. On the whole, the present study demonstrates that the cut-off values of ≥1.30 for the FIB-4 index or ≥-1.455 for the NFS may be used to screen high-risk groups of HCC among patients with non-viral hepatitis. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) occurring in non-cirrhotic livers is often overlooked in clinical practice because the present HCC surveillance strategies usually focus only on patients with cirrhotic livers. This study aimed to determine the risk factors for HCC among viral hepatitis patients with non-cirrhotic livers. The findings of this study could be very useful in detecting HCC at an early stage, especially in patients with viral hepatitis who may not have developed extensive cirrhosis. This study aimed to determine the risk factors for hepatocellular carcinoma in non-cirrhotic livers among viral hepatitis patients. A total of 333 HCC cases, including 69 hepatitis B virus (HBV)-related and 264 hepatitis C virus (HCV)-related, were divided into cirrhotic (Fibrosis-4 [FIB-4] index > 3.25) and non-cirrhotic groups (FIB-4 index ≤ 3.25). The clinical characteristics of the two groups were compared. The independent risk factors for the development of HCC were analyzed using logistic regression analysis. The patients with HBV-related HCC were significantly younger, had better Child-Pugh scores, lower FIB-4 index and Mac-2 binding protein glycosylated isomers (M2BPGi) levels, more progressive cancer stage, and higher alpha-fetoprotein (AFP) levels than those with HCV-related HCC. Diabetes mellitus and hypertension were less common in patients with HBV-related HCC. The non-cirrhotic group with HBV-related HCC had a higher visceral adipose tissue index (VATI), better Child-Pugh score, and higher hemoglobin A1c (HbA1c), whereas the one with HCV-related HCC had a higher proportion of men, higher VATI, better Child-Pugh score, higher HbA1c, and a higher prevalence of hypertension, than the corresponding cirrhotic groups. Logistic regression analyses demonstrated that age, male sex, VATI, HbA1c, the presence of hypertension, and HBV etiology were independent risk factors for HCC in a non-cirrhotic liver. A high accumulation of VAT is a risk factor for HCC in patients with non-cirrhotic livers. [ABSTRACT FROM AUTHOR]

Simple Summary: With the increasing prevalence of obesity and diabetes in most countries, the increase in hepatocellular carcinoma (HCC) associated with these factors has recently become a serious healthcare problem. HCC can often emerge in the non-cirrhotic liver among obese patients, and it might suggest that the conventional surveillance strategies for HCC, which is mainly targeted at cirrhotic patients with hepatitis B or C virus, might be insufficient in the overnutrition era. We tried to extract factors that affect recurrence-free survival in patients with non-viral HCC, among obesity and diabetes factors, together with the established recurrence risk factors, using a decision-tree analysis. We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment. [ABSTRACT FROM AUTHOR]

Recently, treatments for chronic hepatitis C virus (HCV) infection have significantly improved by the development of direct-acting antiviral agents (DAAs) and almost all patients with HCV can complete antiviral treatment without apparent adverse events. Malignant lymphoma, particularly B-cell non-Hodgkin's lymphoma, is one of the extrahepatic manifestations associated with chronic HCV infection. The effectiveness of anti-HCV therapy with DAAs for B-cell non-Hodgkin's lymphoma has been demonstrated in recent reports, whereas late-onset B-cell non-Hodgkin's lymphoma after HCV eradication with DAAs has occasionally been reported. In the present study, a 77-year-old man with chronic hepatitis C and intermediate liver cancer risk received sofosbuvir-ledipasvir treatment for 12 weeks. Two months following the end of antiviral therapy, he had achieved sustained virologic response for 8 weeks. However, the patient occasionally found swelling of the right cervical lymph nodes without any subjective symptoms. Lymph node biopsy revealed diffuse large B-cell lymphoma and whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography showed increased FDG uptake in the right cervical, right submandibular, mediastinal and mesenteric lymph nodes. The patient received six courses of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and achieved complete response at 8 months after chemotherapy initiation. Thus, the development of lymphoid malignancies may arise, even after HCV eradication with DAAs. Therefore, clinicians should be aware of such risks during and after antiviral treatment with DAAs. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the annualized changes in body composition, including skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before, during, and after sorafenib treatment in patients with hepatocellular carcinoma (HCC). This retrospective study evaluated 61 HCC patients treated with sorafenib. Annualized changes (Δ; cm2/m2/year) in skeletal muscle index (SMI), SAT index (SATI), and VAT index (VATI), which were defined as the cross-sectional areas (cm2) of those areas on computed tomography normalized by the square of one's height (m2), before (pre), during (during), and after (post) sorafenib treatment, were calculated. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion group and the effects of these values on survival were analyzed using the Kaplan-Meier analysis and Cox proportional-hazards model. Annualized depletion rates of SMI (ΔSMIpre: −3.5, ΔSMIduring: −3.5, ΔSMIpost: −8.0) and VATI (ΔVATIpre: −3.2, ΔVATIduring: −2.8, ΔVATIpost: −15.1) accelerated after the cancellation of sorafenib, whereas that of SATI (ΔSATIpre: −4.8, ΔSATIduring; −7.6, ΔSATIpost; −8.0) had already accelerated during sorafenib treatment. Patients with rapid depletion of ΔSATIduring experienced significantly worse survival rates (p < 0.001), and it was an independent predictor of survival (p = 0.009), together with therapeutic effect (p < 0.001). Rapid depletion of SAT during sorafenib treatment can be used to predict survival in patients with HCC. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether rapid depletions of fat mass and skeletal muscle mass predict mortality in hepatocellular carcinoma (HCC) patients treated with sorafenib. This retrospective study evaluated 61 HCC patients. The cross-sectional areas of visceral and subcutaneous fat mass and skeletal muscle mass were measured by computed tomography, from which the visceral fat mass index (VFMI), subcutaneous fat mass index (SFMI), and skeletal muscle index (L3SMI) were obtained. The relative changes in these indices per 120 days (ΔVFMI, ΔSFMI, and ΔL3SMI) before and after sorafenib treatment were calculated in each patient. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion (RD) group. Kaplan–Meier analysis revealed that with respect to ΔL3SMI (p = 0.0101) and ΔSFMI (p = 0.0027), the RD group had a significantly poorer survival. Multivariate analysis using the Cox proportional-hazards model also demonstrated that ΔL3SMI (≤−5.73 vs. >−5.73; hazard ratio [HR]: 4.010, 95% confidence interval [CI]: 1.799–8.938, p = < 0.001) and ΔSFMI (≤−5.33 vs. >−5.33; HR: 4.109, 95% CI: 1.967–8.584, p = < 0.001) were independent predictors. Rapid depletions of subcutaneous fat mass and skeletal muscle mass after the introduction of sorafenib indicate a poor prognosis. [ABSTRACT FROM AUTHOR]