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Aging causes skeletal muscle atrophy, and myofiber loss can be a critical component of this process. In 1989, Rosenberg emphasized the importance of the loss of skeletal muscle mass that occurs with aging and coined the term 'sarcopenia'. Since then, sarcopenia has attracted considerable attention due to the aging population in developed countries. The presence of sarcopenia is closely related to staggering, falls and even frailty in the elderly, which in turn leads to the need for nursing care. Sarcopenia is often associated with a poor prognosis in the elderly. Therefore, it is crucial to investigate the causes and pathogenesis of sarcopenia, and to develop and introduce interventional strategies in line with these causes and pathogenesis. Sarcopenia can be a primary component of physical frailty. The association between sarcopenia, frailty and locomotive syndrome is complex; however, sarcopenia is a muscle‑specific concept that is relatively easy to approach in research. In the elderly, a lack of exercise, malnutrition and hormonal changes lead to neuromuscular junction insufficiency, impaired capillary blood flow, reduced repair and regeneration capacity due to a decrease in the number of muscle satellite cells, the infiltration of inflammatory cells and oxidative stress, resulting in muscle protein degradation exceeding synthesis. In addition, mitochondrial dysfunction causes metabolic abnormalities, such as insulin resistance, which may lead to quantitative and qualitative abnormalities in skeletal muscle, resulting in sarcopenia. The present review article focuses on age‑related primary sarcopenia and outlines its pathogenesis and mechanisms.

The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross-sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. Based on the findings of previous studies, male patients with SMI ≤36.2 cm2/m2 and female patients with SMI ≤29.6 cm2/m2 were defined as having sarcopenia. The baseline characteristics, overall survival (OS) rates, progression-free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non-sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child-Pugh A and 67 with Child-Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non-sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non-sarcopenia group (P

To the best of our knowledge, none of the prognostic staging systems for hepatocellular carcinoma (HCC) patients who underwent sorafenib therapy is universally adopted or preferred. In the present study, we aimed to compare prognostic ability among five prognostic systems, including the Japan Integrated Staging (JIS) system, the Barcelona Clinic Liver Cancer classification system, the tumor-node-metastasis classification system, the Cancer of the Liver Italian Program scoring system and the Chinese University Prognostic Index (CUPI) scoring system for HCC patients who received sorafenib therapy. A total of 143 HCC patients treated with sorafenib were analysed. We compared prognostic ability among the five prognostic systems using the likelihood ratio (LR) χ2 test, linear trend χ2 test and concordance index (c-index). Our cohort included 114 men and 29 women. The median patient age was 71 years (range, 45–89 years). A total of 102 patients were classified as Child-Pugh A and 41 as Child-Pugh B, whereas 31 patients (21.7%) had portal vein invasion and 63 (44.1%) extrahepatic metastases. The median survival time was 6.9 months. In the LR χ2 test, the CUPI scoring system had the highest value (35.804), followed by the JIS system (17.469). In the linear trend χ2 test, the CUPI scoring system had the highest value (17.523), followed by the JIS system (15.819). In addition, the JIS system had the highest value in the 6-month c-index (0.659) as well as in the 1-year c-index (0.674). However, the CUPI classification system had the lowest value in the 1-year c-index (0.590). In conclusion, the JIS system may be an appropriate staging system for HCC patients undergoing sorafenib therapy.

Due to varying positive rates of polymerase chain reaction (PCR) amplification, interpretation of conventional PCR results for non-infectious ascites remains problematic. The present study developed a highly sensitive PCR protocol and investigated the positive rate of PCR for the 16S ribosomal (r)RNA gene in non-infectious ascites. Following the design of a new PCR primer pair for the 16S rRNA gene (800F and 1400R), the sequences of PCR products were analyzed and the lower limit for bacterial DNA detection evaluated. The positive rate of PCR for 16S rRNA gene in non-infectious ascites was also evaluated. PCR with the primer pair amplified the genomic DNA of 16S rRNA genes of major disease-causing bacterial strains. Additionally, PCR with this primer pair provided highly sensitive detection of bacterial genomic DNA (lower limit, 0.1 pg of template DNA). When DNA samples isolated from ascites were used, the 16S rRNA gene was amplified independently of the presence of bacterial infection. PCR products contained the genomic DNA fragments of multiple bacterial species. Bacterial genomic DNA can be amplified from all ascitic fluids using a highly sensitive PCR protocol. Careful attention is required to interpret the results based on simple amplification of 16S rRNA gene with conventional PCR.

The present study examined the prognostic ability of our proposed performance status combined Japan Integrated Staging (PS-JIS) system in hepatocellular carcinoma (HCC) patients with liver cirrhosis (LC) comparing with other four prognostic systems including original JIS system, the Barcelona Clinic Liver Cancer classification system, TNM classification system and the Cancer of the Liver Italian Program (CLIP) scoring system. A total of 1,170 HCC patients complicated with LC were analysed. The disease was staged for all analysed patients by means of the five staging systems. The cumulative overall survival (OS) rate was calculated by Kaplan-Meier method and tested by log-rank test. We also examined prognostic factors associated with OS using univariate and multivariate analyses and compared the prognostic ability in each prognostic system using concordance index (c-index) at 1-, 3- and 5-year time-points. Overall significance in each prognostic system was P

We aimed to examine the relationship between the preoperative GSA index [uptake ratio of the liver to the liver plus heart at 15 min (LHL15) to uptake ratio of the heart at 15 min to that at 3 min (HH15) ratio] calculated from 99mTc‑labeled diethylene triamine pentaacetate-galactosyl human serum albumin (99mTc-GSA) scintigraphy and background liver fibrosis and to investigate whether the GSA index can be a useful predictor in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients treated with surgical resection (SR). A total of 213 HCV-related HCC patients were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for nine noninvasive parameters including GSA index, indocyanine green retention at 15 min, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin, platelet count and prothrombin time for cirrhosis. We also examined predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) after SR in univariate and multivariate analyses. There were 153 males and 60 females with the mean age of 69.9 years. The median observation periods were 2.8 years. The mean maximum tumor size was 4.1 cm. HH15 ranged from 0.452 to 0.897. LHL15 ranged from 0.669 to 0.982. The mean value of the GSA index was 1.41. Among the nine parameters, the GSA index yielded the highest AUROC for cirrhosis with a level of 0.786 at an optimal cut-off value of 1.37 (sensitivity, 65.9%; specificity, 79.0%). In multivariate analyses, the GSA index was an independent predictor (P

The aims of the present study were to examine the relationship between the preoperative FIB-4 index and background liver fibrosis in non-tumor parts obtained from surgical specimens and to investigate whether the FIB-4 index can be a useful predictor for non-B non-C hepatocellular carcinoma (NBNC-HCC) patients treated with surgical resection (SR). A total of 118 patients with NBNC-HCC treated with SR with curative intent were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for the FIB-4 index, aspartate aminotransferase (AST) to platelet ratio index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin and platelet count for cirrhosis. We also examined predictors linked to overall survival (OS) and recurrence-free survival (RFS) after SR. The mean patient age was 68.9±9.0 years (93 males and 25 females) with a median observation period of 3.2 years. In extracted surgical specimens, background liver cirrhosis (F4) was observed in 39 patients (33.1%). The mean maximum tumor size was 5.7±3.2 cm. The mean body mass index was 24.3±3.9 kg/m2. The FIB-4 index yielded the highest AUROC for cirrhosis with a level of 0.887 at an optimal cut-off value of 2.97 (sensitivity, 92.3; specificity, 69.6%). In the multivariate analysis, serum α-fetoprotein >40 ng/ml (P=0.026) was the only significant independent predictor linked to OS, while tumor number (P=0.002) and FIB-4 index >2.97 (P=0.044) were significant factors linked to RFS. In conclusion, preoperative FIB-4 index can be a useful predictor for NBNC-HCC patients who undergo SR.

We examined whether supplementation of branched-chain amino acid (BCAA) granules in an early stage of underlying liver disease (pretreatment serum albumin levels ≥ 3.6 g/dl) can improve overall survival (OS) after therapy for hepatocellular carcinoma (HCC) using propensity score matching analysis. We compared OS between patients treated with BCAA granules and control group patients in two propensity score matched cohorts (cohort 1: pretreatment serum albumin levels ≥ 3.6 g/dl and

The aim of the present study was to compare clinical outcomes in patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent the following treatments: transcatheter arterial chemoembolization (TACE) using an epirubicin-mitomycin-lipiodol (EML) emulsion at initial therapy (TACE group; n=145), and transcatheter chemotherapy infusion (TACI) using an EML emulsion at initial therapy (TACI group; n=81). Overall survival (OS) and treatment efficacy in the TACE and TACI groups were retrospectively compared. Prognostic factors associated with OS were examined using univariate and multivariate analyses. Treatment-related mortality was also calculated. The median observation periods were 1.8 years (range, 0.2-9.0 years) in the TACE group and 2.0 years (range, 0.2-8.7 years) in the TACI group. The median survival time and the 1-, 2-, 3- and 5-year cumulative OS rates were 2.68 years and 81.5, 63.4, 43.9 and 32.7%, respectively, in the TACE group, and 2.64 years and 85.0, 60.0, 43.2 and 26.0%, respectively, in the TACI group (P=0.691). The objective response rate was significantly higher in the TACE group compared to the TACI group (80.0 vs. 66.7%; P=0.009). Using multivariate analysis, the Child-Pugh classification (P=0.017), tumor number ≤5 (P=0.045) and des-γ-carboxy prothrombin level >100 mAU/ml (P=0.002) were found to be significant predictors linked to OS. In all subgroup analyses involving Child-Pugh classification, maximum tumor size and tumor distribution, the differences in the two groups did not reach statistical significance in terms of OS. Treatment mortality was 0% in the two groups. In conclusion, patients with intermediate-stage HCC had a comparable prognosis when treated with TACI or TACE.

In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2–11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of

Although most hepatocellular carcinoma (HCC) is related to viral infection, there is a substantial population of HCC patients (5-20%) who are negative for both markers of hepatitis B virus and hepatitis C virus infection [non-B, non-C (NBNC) hepatitis] in Japan and the incidence of NBNC-HCC has recently tended to increase. The most common cause of liver disease in developed countries is non‑alcoholic fatty liver disease (NAFLD), which includes non‑alcoholic steatohepatitis (NASH) and its related complications. Increased body mass index and diabetes mellitus are associated with developing NAFLD and NASH, which is a severe form of NAFLD. Furthermore, increasing clinical evidence supports the fact that NAFLD and NASH can progress to liver cirrhosis and even HCC. A detailed understanding of the epidemiology, etiology, molecular mechanism, clinical features and prognosis of NBNC-HCC could improve our screening and therapy of this disease. In this review, we primarily focus on clinical aspects of NBNC-HCC and refer to our current knowledge of this cancer.

The impact of antibodies to hepatitis B core antigen (anti-HBc) on survival after curative surgical resection (SR) for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the relationship between anti-HBc positivity and survival of HCV-related HCC patients who underwent curative SR. A total of 222 patients with HCV-related, hepatitis B surface antigen (HBsAg)-negative HCC who underwent curative SR were analyzed. They included 119 anti-HBc-positive patients (53.6%) and 103 anti-HBc-negative patients (46.4%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. The median follow-up periods in the anti-HBc-positive and anti-HBc-negative groups were 3.4 years (range, 0.3-10.9 years) and 3.2 years (range, 0.5-10.9 years), respectively. The 1-, 3- and 5-year cumulative OS rates were 88.8, 70.2 and 50.0%, respectively, in the anti-HBc-positive group and 95.8, 77.1 and 61.7% in the anti-HBc-negative group (P=0.300). The corresponding RFS rates were 68.7, 33.0 and 20.0%, respectively, in the anti-HBc-positive group and 74.4, 38.5 and 16.5% in the anti-HBc-negative group (P=0.482). Multivariate analyses identified serum albumin ≥3.8 g/dl (P=0.005) and the presence of microvascular invasion (P

The value of serum cholinesterase (ChE) level as a predictive marker in sorafenib therapy for advanced hepatocellular carcinoma (HCC) has not yet been investigated. The present retrospective study therefore analyzed the impact of the serum ChE level in 93 patients with advanced HCC treated with sorafenib. Patients were categorized into two groups: group A with pretreatment serum ChE ≥140 IU/l (n=46) and group B with pretreatment serum ChE

The aim of the present study was to evaluate the influence of preoperative transcatheter arterial chemoembolization (TACE) on survival after surgical resection (SR) for hepatocellular carcinoma (HCC). Two hundred and thirty-five HCC patients who underwent SR with curative intent were analyzed. Overall survival (OS), recurrence-free survival (RFS) and complication rates were compared between the TACE (n=110) and control groups (n=125). Moreover, TACE subjects were classified into TACE responders (n=85) and TACE non-responders (n=25), according to the therapeutic efficacy of pretreatment TACE, and the factors contributing to OS and RFS after SR were analyzed using univariate and multivariate analyses. The 1-, 3- and 5-year OS rates were 87.4, 76.0 and 62.5%, respectively, in the TACE group and 94.9, 79.0 and 57.8%, respectively, in the control group (P=0.674). The corresponding RFS rates at 1, 3 and 5 years were 73.3, 48.9 and 33.2%, respectively, in the TACE group and 73.3, 29.4 and 16.3%, respectively, in the control group (P=0.062). No TACE-related serious adverse events (SAEs) were observed. There were no significant differences between the groups in terms of surgery-related SAEs (P=0.714), operation time (P=0.881), blood loss during surgery (P=0.334) and hospitalization period (P=0.447). Multivariate analyses identified TACE responder, TACE non-responder, total bilirubin ≥1 mg/dl, serum albumin ≥4 g/dl, pretreatment α-fetoprotein (AFP) level ≥100 ng/ml and microscopic vascular invasion as significant prognostic factors linked to OS. TACE non-responder, tumor number (multiple) and pretreatment AFP level ≥100 ng/ml were significant adverse prognostic factors linked to RFS. In conclusion, TACE is a safe procedure in patients with HCC, and the efficacy of TACE prior to surgery may be associated with clinical outcomes after SR.