Serum zinc concentration as a potential predictor of presarcopenia in patients with chronic liver disease: a preliminary study.

Background: Presarcopenia is a common complication of chronic liver disease. However, the relationship between serum zinc concentration and presarcopenia in patients with chronic liver disease remains unclear. Herein, we examined whether serum zinc concentration could predict presarcopenia in patients with chronic liver disease. Methods: Between October 2015 and December 2019, 278 patients with chronic liver disease (median age, 68 years; women/men, 133/145; hepatitis B virus/hepatitis C virus/negative hepatitis B surface antigen and negative anti-hepatitis C virus antibody, 55/124/99) who underwent abdominal computed tomography (CT) and simultaneous measurement of serum zinc concentration were included. Zinc deficiency and subclinical zinc deficiency were classified using serum zinc concentration cutoff values of <60 and <80 µg/dL [based on the Japanese Society of Clinical Nutrition (JSCN) guidelines], respectively. Additionally, presarcopenia was evaluated based on the skeletal muscle mass as per the Japan Society of Hepatology (JSH)'s sarcopenia criteria. Results: Univariate analysis revealed that the following factors were significantly associated with the presence of presarcopenia in patients with chronic liver disease: age (P<0.001), male sex (P<0.001), body mass index (BMI) (P<0.001), serum zinc concentration (P=0.005), fibrosis-4 index (P<0.001), and serum albumin concentration (P=0.03). Additionally, the median L3 skeletal muscle indices were as follows: men, non-presarcopenia group/presarcopenia group, 47.56/37.91 cm2/m2 (P<0.001); women, non-presarcopenia group/presarcopenia group, 41.64/32.88 cm2/m2 (P<0.001). Multivariate analysis using logistic regression analysis revealed that male sex [odds ratio (OR), 0.194; 95% confidence interval (CI): 0.089-0.419; P<0.001], BMI (OR, 0.666; 95% CI: 0.582-0.761; P<0.001), and serum zinc concentration <60 µg/dL (OR, 5.930; 95% CI: 1.480-23.80; P=0.01) were factors associated with presarcopenia. The OR for serum zinc concentration between 60 and 80 µg/dL was 1.910 (95% CI: 0.824-4.420; P=0.13). Conclusions: Low serum zinc levels may be an independent predictor of presarcopenia in patients with chronic liver disease.

Optimal Skeletal Muscle Mass Index Cut-Off Values for Presarcopenia Evaluated by Computed Tomography against Dual-Energy X-ray Absorptiometry in Patients with Chronic Liver Disease.

Although dual-energy X-ray absorptiometry (DXA) and body impedance analysis are commonly used to measure skeletal muscle mass (SMM), a computed tomography (CT) scan is preferred in clinical practice. We aimed to propose the cut-off values of skeletal muscle mass index (SMI) calculated using CT scans, using DXA as the reference method. We retrospectively assessed 589 patients with chronic liver disease. The SMI was assessed using appendicular SMM by DXA and total muscle area at the level of the third lumbar vertebra (L3) calculated by CT. The cut-off value was determined with reference to the Asian Working Group for Sarcopenia criteria. DXA identified 251 (42.6%) patients as having presarcopenia. In men, the cut-off value of SMI for presarcopenia was determined to be 45.471 cm2/m2, with an area under the curve (AUC) of 0.863 (95% confidence interval (CI): 0.823 to 0.903), and in women, this value was determined to be 35.170 cm2/m2, with an AUC of 0.846 (95% CI: 0.800 to 0.892). Cohen's kappa coefficient was 0.575 (95% CI: 0.485-0.665) in men and 0.539 (95% CI: 0.438-0.639) in women.

Effect of levocarnitine administration in patients with chronic liver disease.

L-carnitine administration was reported to improve sarcopenia in patients with cirrhosis. However, the amount of evidence from previous studies is not sufficient. The present study aimed to clarify the effect of levocarnitine (L-carnitine) administration on body composition in patients with chronic liver disease (CLD). In the present study, 85 patients with L-carnitine administration and 87 control patients were enrolled and divided them into two groups, the L-carnitine administration group (LAG, n=44) and the without L-carnitine administration (controls, n=44) group, by using propensity score matching for age, sex, body mass index (BMI) and serum albumin. Δ skeletal muscle mass index (SMI)/year, Δ intramuscular adipose tissue content (IMAC)/year and Δ bone mineral density (BMD)/year were examined during L-carnitine administration. Each parameter was measured by computed tomography (CT) or dual-energy X-ray absorptiometry. The median age overall was 69 years (IQR, 64.0, 75.0); 36 were men and 52 were women. The median SMI was 37.4 cm2/m2 (IQR, 34.01, 44.34). The initial CT scans showed similar median values of SMI for the two groups [37.74 (34.17, 43.58) and 37.16 (33.83, 44.34), P=0.67]. However, the median ΔSMI/year for the LAG and controls were 0.95% (-3.07, 6.10) and -2.34% (-5.34, 0.53), respectively (P=0.003). The median Δ whole body BMD/year for the LAG and controls were -0.24% (-1.20, 0.91) and -1.04% (-2.16, 0.47), respectively (P=0.038). The median ΔIMAC/year and Δ lumbar spine BMD were not significantly different between the LAG and controls. L-carnitine administration may prevent the loss of skeletal muscle mass and BMD; therefore, it may be used as a new treatment option for osteoporosis and sarcopenia in patients with CLD.

Advanced Age is not a Risk Factor for Mortality in Patients with Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Organisms: a Multicenter Cohort Study.

A 5-year multicenter retrospective cohort study was conducted across six hospitals in Niigata, Japan. Patients (n = 179) with bacteremia due to extended-spectrum ß-lactamase (ESBL)producing organisms were included in the study. The rates of appropriate carbapenem prescription were 61% (n = 41) in patients aged 65-84 years and 89% (n = 31) in those aged ≥ 85 years. Patients aged ≥ 85 years were significantly more likely to receive carbapenem than their younger counterparts. After propensity score matching, 65 patients were assigned to two groups based on age (65-84 years or ≥ 85 years). Multivariate regression analysis showed that other sites of infection had a positive association with 30-day mortality (odds ratio [OR], 27.50; 95% confidence interval [CI], 2.90-260.00) and biliary tract infection tended to have a positive association with 30-day mortality (OR, 8.90; 95% CI, 0.88- 89.90) compared with urinary tract infection. However, an age ≥ 85 years was not associated with 30-day mortality. Elderly patients aged ≥ 85 years were more likely to be treated with carbapenem; however, old age was not associated with 30-day mortality when bacteremia was caused by ESBLproducing organisms. These results may help clinicians justify withholding carbapenem in patients aged ≥ 85 years.

Efficacy of Physical Activity in Prevention of Muscle Weakness in Patients With Chronic Liver Disease.

BACKGROUND: Sarcopenia is a prognostic factor for patients with liver cirrhosis and hepatocellular carcinoma, and it affects the onset of hepatic encephalopathy. Therefore, the prevention of sarcopenia contributes to the improvement of the prognosis of patients with chronic liver disease (CLD). We focused on changes of hand grip strength (HGS), one of the indicators of sarcopenia. However, there are little data investigating the impact of physical activity (PA) on HGS in patients with CLD. This study aimed to clarify whether PA contributes to the prevention of muscle weakness in patients with CLD. METHODS: This was a prospective observational study. We examined the effect of PA on changes in HGS from the baseline to the endpoint in each group. Metabolic equivalents-hour/week (METs-h/w) was used to evaluate PA. In total, 183 outpatients with CLD were analyzed. We divided participants into four groups (low PA in younger patients (n = 20), high PA in younger patients (n = 33), low PA in elderly patients (n = 47), and high PA in elderly patients (n = 83)). RESULTS: Fifty-eight percent of patients were men, and the median (interquartile range) age was 69.0 (63.0, 75.0) years. The most common etiology of liver disease was hepatitis C (38%). The frequency of living alone and low exercise habit was significantly high, and sarcopenia was more obvious in elderly patients with low PA than in those with high PA. Additionally, the elderly with low PA showed significantly reduced HGS compared to that of the elderly with high PA (-1.00 (-2.27, 0.55) kg vs. 0.10 (-1.40, 1.10) kg, P < 0.05). However, changes in HGS in younger patients were not significant (-0.02 (1.83, 1.47) kg vs. 0.25 (-2.45, 2.05) kg, P = 0.96). Logistic regression analyses identified PA as the independent factor for prevention of decrease in HGS (odds ratio: 1.91, 95% confidence interval: 1.00 - 3.62, P = 0.049). CONCLUSIONS: Young patients with low PA were characterized by a long sedentary time; however, there was no loss of HGS. In contrast, elderly patients with CLD and low PA had significantly reduced HGS compared to that in elderly patients with CLD and high PA.

Relationship between pre-sarcopenia and quality of life in patients with chronic liver disease: a cross-sectional study.

AIM: This study aimed to clarify the relationship between pre-sarcopenia (PS) and quality of life (QOL) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: This cross-sectional study evaluated 335 patients with CLD. PS was diagnosed on the basis of the assessment criteria by the Japan Society of Hepatology. QOL was evaluated using the short form-36. RESULTS: Patients' mean age was 69.52 ± 10.17 years, and 169 (50.4%) participants were men. The prevalence of PS was 53.7%. Patients were divided into the PS and non-pre-sarcopenia (NPS) groups. Patients in the PS group were older (71.84 ± 9.78 vs. 66.81 ± 9.97, P < 0.01) and mostly women (65.2 vs. 37.8%, P < 0.01) compared with those in the NPS group. QOL, physical function (38.30 ± 17.63 vs. 44.02 ± 14.76, P < 0.01), physical role functioning (RP) (40.63 ± 15.38 vs. 44.88 ± 13.89, P < 0.01), and bodily pain (BP) (48.42 ± 11.45 vs. 51.24 ± 10.19, P = 0.02) were significantly lower in the PS group than in the NPS group. Logistic regression analyses identified that the independent predictive factors for PS were female sex (odds ratio: 3.16, 95% confidence interval: 2.01-4.98; P < 0.01) and RP (odds ratio: 1.97, 95% confidence interval: 1.24-3.12; P < 0.01). CONCLUSION: QOL characteristics of PS patients with CLD were low physical function, RP, and BP in short form-36. In addition, social role functioning was low in the PS patients aged 65-74 years, whereas RP and BP were low in those aged at least 75 years. Female sex and RP were independent predictors of PS according to the multivariate analysis. Maintaining and increasing muscle mass in patients with CLD may contribute toward improving physical QOL.

Relationship Between Sarcopenia and Both Physical Activity and Lifestyle in Patients With Chronic Liver Disease.

BACKGROUND: Sarcopenia can affect the prognosis of patients with cirrhosis or hepatocellular carcinoma. Exercise therapy and nutritional therapy are carried out to prevent processing sarcopenia. In addition, changing lifestyle is also important. However, there are only few reports on the physical activities (PAs) and lifestyle of chronic liver disease patients and their association with sarcopenia. The aim of this study is to examine the relationship between sarcopenia in patients with chronic liver disease and both PA and lifestyle. METHODS: A total of 214 out-patients with chronic liver disease were enrolled into the present study. All patients were evaluated for with or without sarcopenia based on the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Then, patient's characteristics and laboratory parameters were divided into two groups with or without sarcopenia and compared. In continuous variable with significant difference in univariate analysis, cut-off value was calculated by receiver operating characteristic curve. We determined which factors were associated with sarcopenia in univariate analyses, and variables significant in the univariate analyses were entered in a multivariable logistic regression model. RESULTS: Patients with chronic liver disease had a prevalence of sarcopenia of 12.6% in this study. Sarcopenia patients were older (76.48 ± 6.69 versus 66.97 ± 11.19 years old; P < 0.01), had lower body mass index (BMI) (20.84 ± 2.44 versus 23.76 ± 3.72 kg/m2; P < 0.01), lower PA (6.6 (2.34 - 19.90) versus 16.5 (6.60 - 41.23) metabolic equivalents (METs)-h/week; P < 0.01) and longer total time sitting and lying on the day (7.43 ± 4.09 versus 5.68 ± 3.17 h/day; P = 0.01); retirement status (81.5% versus 48.1%; P < 0.01) and low frequency of driving (40% versus 20%; P = 0.01) were higher in sarcopenia patients than in non-sarcopenia patients. The independent predictive factors of sarcopenia, analyzed with logistic regression, were age (odds ratio (OR): 5.89, 95% confidence interval (CI): 2.15 - 16.20; P < 0.01), BMI (OR: 4.77, 95% CI: 1.87 - 12.10; P < 0.01) and PA (OR: 3.65, 95% CI: 2.15 - 16.20; P < 0.01). CONCLUSION: Sarcopenia patients' lifestyle characteristics were longer sedentary time and low frequency of driving, high retirement. Independent predictive factors of sarcopenia were elderly, low BMI and low PA. For these patients, intervention in the lifestyle for prevention of sarcopenia may be effective for patients with chronic liver disease.

Health-related quality of life on the clinical course of patients with chronic hepatitis C receiving daclatasvir/asunaprevir therapy: A prospective observational study comparing younger (<70) and elderly (≥70) patients.

Interferon-free direct acting antiviral agent regimens for chronic hepatitis C (CHC) have been developed. These regimens have shown a high rate of sustained virologic response (SVR), and a reduction in side effects during treatment is also anticipated. However, the impact of the regimens on health-related quality of life (HRQOL) and side effects during treatment is not fully understood. The purpose of the present study was to evaluate HRQOL in the clinical course of patients with CHC receiving daclatasvir/asunaprevir (DCV/ASV) therapy using the Short Form-36 (SF-36) method. Twenty-eight patients with CHC receiving DCV/ASV therapy were analyzed in the present study, and HRQOL was measured by SF-36. Patients were asked to fill out the SF-36 prior to therapy (baseline), following 12 weeks of therapy, at the end of treatment and at SVR week 24 (SVR24) to evaluate HRQOL. Laboratory data were also investigated during the same period, and associations between these results and SF-36 were investigated. Aspartate aminotransferase, alanine aminotransferase, serum albumin, α-fetoprotein, platelet counts and Fibrosis (Fib)-4 index were all significantly improved at each time point when compared with baseline. With regard to alterations in HRQOL during therapy, the ≥70-year-old group displayed a significantly greater improvement in physical functioning during the period between baseline and 12 weeks when compared with the <70-year-old group. In the analysis of the SF-36 differences within each group, general health improved significantly in the ≥70-year-old group, as well as albumin levels. In addition, Fib-4-index significantly improved at all time points (12 and 24 weeks, and SVR24) when compared with baseline in the ≥70-year-old group. Therefore, DCV/ASV therapy may improve HRQOL and hepatic functional reserve, particularly in elderly patients.

Evaluation of the health-related quality of life using the 36-item short form health survey in patients with chronic hepatitis C receiving pegylated interferon/ribavirin/telaprevir triple treatment.

The rate of sustained virologic response (SVR) has increased in patients with chronic hepatitis C (CHC; genotype 1) since triple treatment with pegylated interferon (PEG-IFN), ribavirin (RBV) and telaprevir (TVR) was included in Japanese health insurance. However, side effects such as high-grade anemia and skin disorders means it is important to investigate the extent to which quality of life (QOL) is maintained during treatment. The impact on health-related (HR) QOL, as a result of TVR-based triple treatment was investigated long-term (48 weeks) in 34 patients (18 men, 16 women) following TVR-based triple treatment, using the 36-item short form health survey (SF-36). While scores for physical health were significantly lower during treatment, an improvement was seen in patients who showed complete response to treatment from 12 weeks following treatment (P<0.05). HRQOL improved significantly following completion of TVR-based triple treatment in these complete-responders, with higher scores compared with those prior to treatment. Anemia and skin symptoms appeared frequently during treatment and scores for physical health dropped. Particular care needs to be taken in regards to the management of side effects during TVR treatment. Further evaluations using the SF-36 may help in controlling doses to achieve SVR.

Assessment of tear concentrations on therapeutic drug monitoring. III. Determination of theophylline in tears by gas chromatography/mass spectrometry with electron ionization mode.

A simple and sensitive method for the quantitation of theophylline (TP) in tears and plasma developed using gas chromatography/electron-impact ionization/mass spectrometry. Tears were collected by non-invasive Schirmer method. Plasma was pipetted on a Schirmer tear test strip (cutting to 5 mm x 5 mm). Then, TP was converted directly into its pentafluorobenzoyl amide derivative without the need to perform any extraction from the biological fluid absorbed on Schiemer test paper and was quantified by gas chromatography-selected ion recordings with electron ionization mode. The concentrations in tears [C]t correlated very well with those of the free form in the plasma [Cf]p and those of the total form in the plasma [Cb+f]p. The ratios between TP concentrations in tears and plasma (free and total form) were as follows: [C]t/[Cb+f]p=0.53+/-0.20; [C]t/[Cf]p=1.21+/-0.19; [Cf]p/[Cb+f]p=0.44+/-0.14. The ratios of [C]t/[Cb+f]p, [C]t/[Cf]p and [Cf]p/[Cb+f]p were in good agreement with the previously published data.

Viral infection of infants and children with benign transient hyperphosphatasemia.

In this study, we screened serum samples for transient hyperphosphatasemia (TH) using cellulose acetate membrane electrophoresis over a period of 3 years. In the patients found to suffer from TH, we examined the relationship between the clinical condition and viral infection. The frequency of TH was 0.26%, and all of the cases detected were in infants or young children. The female to male ratio of TH was 1.29/1. While there was no clear seasonal fluctuation or periodicity in the appearance of TH, two peaks were recognized in spring and autumn. Research on the clinical manifestations clarified that most of the TH cases had infectious diseases of the upper airways accompanied by symptoms of fever and diarrhea. We examined antibody titers for viruses causing upper airway infectious diseases and identified antibodies for enteroviruses such as Echo 22, Entero 71, and Coxsackie B4. Our results suggested that TH might be caused by an infection of the enterovirus group.