Comparison of calculated body muscle mass and SARC-F as methods of screening for sarcopenia in patients with chronic liver disease.

A simple method is required to screen for sarcopenia in patients with chronic liver disease. In the present study, the value of the existing SARC-F questionnaire as well as calculated body muscle mass (CBMM) approaches were assessed for screening of sarcopenia. A total of 482 patients with chronic liver disease underwent CBMM, grip strength (GS) and SARC-F score assessments. Cross-sectional computed tomography images of the third lumbar vertebrae were analyzed to determine the skeletal muscle (SM) mass in 303 patients. Cutoff CBMM values for sarcopenia were <27.903 in females and <39.731 in males. The cutoff SARC-F score for sarcopenia was ≥4 points. Sarcopenia was diagnosed using the criteria described in the Japan Society of Hepatology. GS was moderately correlated with SARC-F score (females, R=-0.578; males, -0.453) and CBMM (females, R=0.497; males, 0.548). The SM index was moderately correlated with CBMM for both sexes (females, R=0.546; males, 0.612), but not with SARC-F score in females (females, R=-0.132; males, -0.246). The area under the curve (AUC) for CBMM against sarcopenia (0.85964) was significantly larger than that for SARC-F score (0.72013) amongst males (P=0.03577) but not females. The AUCs for a modified SARC-F questionnaire (encompassing the SARC-F questionnaire, CBMM, sex and age; mSARC-F) against sarcopenia were 0.864 in males and 0.78185 in females. As a screening method, SARC-F is less useful than CBMM. However, the AUC for mSARC-F is greater than SARC-F and CBMM.

Direct-acting Antivirals Improved the Quality of Life, Ameliorated Disease-related Symptoms, and Augmented Muscle Volume Three Years Later in Patients with Hepatitis C Virus.

Objective Patient-reported outcomes (PROs) are important measures of the quality of life (QOL) and symptoms in patients with hepatitis C virus (HCV). We evaluated the PROs at the beginning of direct-acting antiviral (DAA) treatment and three years later. A low QOL in patients with chronic liver disease suggested a low muscle mass. We compared the relationship between the QOL and muscle mass. Methods DAAs were administered to 100 patients with HCV infection. The PROs included the cirrhosis-related symptom score (CSS), presence of restless legs syndrome, Pittsburg sleep quality index (PSQI) to evaluate sleep disturbance, SF-36 to measure the QOL, and calculated body muscle mass (CBMM) measured at the beginning of treatment and three years later. Computed tomography (CT) was used to screen 82 patients for hepatocellular carcinoma at the beginning of treatment and three years later. Cross-sectional CT images of the third lumbar vertebrae were analyzed to evaluate the body composition. Results The general health perception (GHN) of SF-36 was better at three years after DAA administration than at the beginning. Changes in the GHN (dGHN) were related to an improved sleep quality on the PSQI and CSS and increased CBMM. The dGHN was positively related to changes in the skeletal muscle. The sleep quality, sleep latency, fatigue, and abdominal fullness were related to dGHN. Conclusion The QOL is related to sleep disturbance and several other symptoms. Furthermore, in patients with an increased muscle volume after DAA treatment, increased muscle mass is associated with an improvement in the QOL.

Indices calculated by serum creatinine and cystatin C as predictors of liver damage, muscle strength and sarcopenia in liver disease.

Serum creatinine (Cr)-based glomerular filtration rate (CrGFR) is overestimated in liver disease. The present study evaluated whether the difference in CrGFR and cystatin C (CysC) GFR (dGFR) is significant in liver disease. The Cr-to-CysC ratio and sarcopenia index (SI) have been reported to correlate with muscle volume. An estimated total body muscle mass with Cr, CysC and calculated body muscle mass (CBMM) has also been reported to correlate with muscle mass. The applicability of dGFR, SI and CBMM for liver disease were evaluated. A total of 313 patients with liver damage were evaluated for Child-Pugh score, albumin-bilirubin (ALBI) score, model for end-stage liver disease, fibrosis-4, Cr, CysC, Cr-based estimated GFR (CreGFR), CysCGFR and grip strength. Of the 313 patients, 199 were evaluated using cross-sectional computed tomography (CT) of the third lumbar vertebra to determine the skeletal muscle (SM) mass. dGFR, CBMM and SI were compared to liver damage, muscle strength and muscle mass. In the 313 patients, dGFR was correlated with age, ALBI and grip strength; CBMM was correlated with body mass index (BMI) and grip strength; and SI was correlated with BMI and grip strength. In patients evaluated with CT, the correlation coefficients for CBMM and SI with SM were 0.804 and 0.293, respectively. Thus, CBMM and SI were associated with sarcopenia. The relationship between dGFR and ALBI does not differ with different grades of CrGFR-based chronic kidney disease (CKD). dGFR is a marker of liver damage and muscle strength regardless of CKD. CBMM and SI are markers for sarcopenia in liver disease.

Calculated body muscle mass as a useful screening marker for low skeletal muscle mass and sarcopenia in chronic liver disease.

AIM: Sarcopenia is a harmful condition in patients with chronic liver disease. However, the evaluation of body muscle mass requires expensive instrumentation. The sarcopenia index (SI): (creatinine / cystatin C × 100) has been reported to correlate with muscle volume. A calculated body muscle mass (CBMM) using creatinine, cystatin C, and bodyweight also correlates with muscle mass. We evaluated the applicability of using SIs and CBMMs as screening methods for sarcopenia. METHODS: Patients (n = 303) with liver damage were evaluated for creatinine, cystatin C, and grip strength (GS). All patients were evaluated using cross-sectional computed tomography images of the third lumbar vertebrae to determine their skeletal muscle (SM) mass. CBMMs and SIs were compared with SMs, GSs, and sarcopenia. RESULTS: Correlation coefficients (R) between SMI (SM / height2 [m2 ]) and CBMM, and between GS and CBMM were 0.643 and 0.723, respectively. Factors contributing to low GSs; low SM indices; and sarcopenia were age and SM; sex, age, GS, SI, and CBMM indices; and sex, bodyweight, and CBMM, respectively, in the multivariate logistic analyses. Receiver operating characteristic curve analysis between sarcopenia and CBMM showed an area under the receiver operating characteristic curve of 0.78504 in women and 0.86067 in men. Cut-off CBMM values for sarcopenia were 27.903 (sensitivity 0.73958) in women and 39.731 (sensitivity 0.7941) in men. CONCLUSIONS: CBMMs and SIs are simple and minimally invasive screening methods in which low levels are indicative of sarcopenia in patients with liver disease.

Changes in serum LDL, PCSK9 and microRNA-122 in patients with chronic HCV infection receiving Daclatasvir/Asunaprevir.

The present study evaluated the changes in lipid profile, and the associations between serum protein convertase subtilisin/kexin 9 (PCSK9), microRNA (miR)122 and low-density lipoprotein variation following treatment of hepatitis C virus (HCV) genotype 1b infection with Daclatasvir/Asunaprevir. A total of 39 patients with HCV genotype 1b infection with chronic hepatitis received a 24-week treatment regimen of Daclatasvir/Asunaprevir. Laboratory data were obtained for each subject every 4 weeks during treatment and every 12 weeks after treatment. Serum miR122 and PCSK9 were measured at the start of treatment (week 0), end of treatment (week 24), 4 weeks after the end of treatment (week 28), 12 weeks after the end of treatment (week 36) and 28 weeks after the end of treatment (week 52). LDL was increased at week 4 after the start of treatment to week 52. The increased LDL/HDL ratio at week 52 compared with week 4 was also associated with relative miR122 at week 52. At week 4, PCSK9-active form (A) was lower than that at other time points, and PCSK9-inactive form (I) exhibited the greatest increase. At week 52, PCSK9-A was higher than that during treatment, but PCSK9-I level at week 52 did not markedly differ from that any time point except for week 4. Relative miR122 at week 4 was associated with increased PCSK9-A at weeks 36 and 52 from the start of DAA. In summary, treatment of HCV with Daclatasvir/Asunaprevir resulted in elevated LDL, and relative miR122 and PCSK9-A levels in serum appeared to have some association with LDL increase.

Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection.

Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.

Hepatitis C virus-related symptoms, but not quality of life, were improved by treatment with direct-acting antivirals.

AIM: Direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection have a significantly high sustained virologic response rate after a short treatment course and do not have any severe adverse effects. Patient-reported outcomes (PROs) have become increasingly important to assess the total impact of a chronic disease. We aimed to evaluate the changes in symptoms of patients with HCV infection treated with DAAs by using PROs. METHODS: A total of 107 patients with chronic HCV infection were treated with DAAs. Daclatasvir/asunaprevir or sofosbuvir/ledipasvir was used for HCV 1B infection, and sofosbuvir/ribavirin for HCV 2A/2B infection. The PROs measured at the start of treatment and 1 year after the start of treatment were cirrhosis-related symptom score (CSS), presence of restless legs syndrome (RLS), Epworth sleepiness scale (ESS), Pittsburg sleep quality index (PSQI), Kessler 6 score (K-6), and the SF-36 to measure quality of life (QOL). All patients had a sustained virologic response rate of 24. RESULTS: The CSS, PSQI, K-6, and RLS scores were improved 1 year after beginning treatment. However, QOL had not recovered. Changes in total CSS were correlated with HCV genotype, sex, hypertensive drug use, serum low-density lipoprotein, and ESS at the start of treatment and RLS 1 year after the start of treatment. The factors that contributed to worsening of CSS were HCV genotype 2B and RLS 1 year after the start of treatment. CONCLUSION: Treatment with DAAs eliminated HCV-RNA and improved most symptoms, but QOL did not recover.

Photodynamic therapy using talaporfin sodium (Laserphyrin®) for bile duct carcinoma: a preliminary clinical trial.

The efficacy of adjuvant photodynamic therapy (PDT) using the new photosensitizer, talaporfin sodium (TPS), was assessed in 7 patients with bile duct carcinoma (BDC). The 664-nm semiconductor laser (100 J/cm(2)) was applied through endoscopy to the tumor lesion within 6 h after injection of TPS. Cases included three non-resectable and 4 resected BDC with remnant cancer cells at the bile duct stump. Radiated lesions exhibited mild inflammatory responses. Locally advanced tumor occluding bile duct was relieved by PDT and patency was maintained for 16 months. Two patients developed mild photodermatitis but no severe morbidity. One patient died of other disease, and two patients died of liver metastasis within 6 months, but local recurrence was not observed. Three patients maintained cancer-free survival for 6-13 months. One patient survived with good status for 24 months. Adjuvant TPS-PDT is a safe and useful treatment for local control of BDC. Compared to the conventional PDT, the patient's quality of life is remarkably improved.

Evaluation of surgical resection for gallbladder carcinoma at a Japanese cancer institute.

BACKGROUND/AIMS: Surgical resection is a radical treatment option for gallbladder carcinoma (GBC); however, it is still difficult to cure and patient prognosis is poor. An assessment of the surgical results and chemotherapy options may elucidate effective treatments. METHODOLOGY: We retrospectively examined the demographics, surgical records and outcome in 33 patients with GBC undergoing surgical resection. RESULTS: Postoperative cancer recurrence was observed in 36% of patients. Mean cancer-free survival time was 84 months and 3-year cancer-free survival rate was 70% Mean overall survival time was 96 months and 5-year overall survival rate was 52%. The 3-year cancer-free survival and the 5-year overall survival were significantly different between the final tumor stages (p<0.001). Higher CEA and CA19- 9 level were significantly related to poor overall survival (p<0.05). Macroscopically, papillary type tumor showed significantly better overall survival compared to nodular or flat types (p<0.05). Degree of invasion, node metastasis, moderate or poor differentiation, vascular or perineural invasion and invasion of the liver or hepatoduodenal ligament were significantly associated with poor overall survival (p<0.05). A cancerfree margin at the hepatic cut end and dissected periductal structures showed a significantly poor prognosis (p<0.05). The overall survival in final curability A was significantly associated with better curability than B or C (p<0.05). CONCLUSIONS: Radically extended surgical resection for GBC is necessary to obtain improved patient survival and new adjuvant chemotherapy would be expected to improve results after surgery.