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.

Comparison of Ablation Volume Between Emprint® and Mimapro® Systems for Hepatocellular Carcinoma -A Preliminary Study.

Background: Microwave ablation (MWA) is a standard percutaneous local therapy for hepatocellular carcinoma (HCC). Next-generation MWA is reported to create a more spherical ablation zone than radiofrequency ablation (RFA). We compared the ablation zone and aspect ratio of two 2.45 GHz MWA ablation probes; Emprint® (13G) and Mimapro® (17G). We compared the ablation zone to the applied energy after MWA in patients with hepatocellular carcinoma (HCC). Furthermore, we investigated local recurrence. Materials and Methods: We included 20 patients with HCC, with an average tumour diameter of 33.2 ± 12.2 mm, who underwent MWA using Emprint®, and 9 patients who underwent MWA using Mimapro® with an average tumour diameter of 31.1 ± 10.5 mm. Both groups underwent the same ablation protocol using the same power settings. The images obtained after MWA showed the treatment ablation zone and aspect ratio, which were measured and compared using three-dimensional image analysis software. Results: The aspect ratios in the Emprint® and Mimapro® groups were 0.786 ± 0.105 and 0.808 ± 0.122, respectively, with no significant difference (p = 0.604). The ablation time was significantly shorter in the Mimapro® group than in the Emprint® group, and there was no significant difference in the frequency of popping or the ablation volume. There were no significant differences in local recurrence between the two groups. Conclusion: There was no significant difference in the aspect ratios of the ablation diameter, and the ablation zone was almost spherical in both cases. Mimapro® at 17G was less invasive than Emprint® at 13G.

Ex Vivo Experimental Study of the Ablation Area of Bovine Liver Using STARmed Radiofrequency Ablation.

BACKGROUND/AIM: Ablating a spherical area during hepatocellular carcinoma ablation therapy is a very important issue. We aimed to determine the ablation area of bovine liver using various radiofrequency ablation (RFA) protocols. MATERIALS AND METHODS: Bovine liver (1-2 kg) was placed in an aluminum tray, which was punctured with STARmed VIVA 2.0 17-gauge (G) and 15-G electrodes using a current-carrying tip. Under the step-up or linear method, with an ablation time up to one break and RFA output stop, the size of the color change area (representing the thermally coagulated area) of the bovine liver was measured along the vertical and horizontal axes, and the ablated volume and total heat generated were calculated. RESULTS: 5-W per minute increases protocol resulted in greater horizontal and vertical diameters of the ablated area than 10-W per minute increases protocol under the step-up method. For 5-W and 10-W per minute increases under the step-up method, the aspect ratio was 0.81 and 0.67 with a 17-G electrode, and 0.73 and 0.69 with a 15-G electrode, respectively. For 5-W and 10-W increases under the linear method, the aspect ratio was 0.89 and 0.82, respectively. Sufficient ablation was obtained, with vertical and horizontal diameters of 50 mm and 43.50 mm, respectively. Although the ablation time was long, the watt output value at the break and average watt value were low. CONCLUSION: Gradual increase in output (5 W) using the step-up method yielded a more spherical ablation area, and longer ablation time in the linear method with a 15-G electrode could result in a more spherical ablation area in real clinical practice in humans. Future studies should examine concerns regarding long ablation times.

An Investigation of Popping During Radiofrequency Ablation After Lenvatinib Administration for Hepatocellular Carcinoma.

BACKGROUND/AIM: Lenvatinib is available as a molecular target agent for hepatocellular carcinoma (HCC). In this study, we investigated the popping phenomena in patients with HCC who underwent radiofrequency ablation (RFA) after taking lenvatinib. PATIENTS AND METHODS: Fifty-nine patients with HCC between 21-30 mm in diameter and no history of systemic treatment were enrolled in the study. The patients underwent RFA using a VIVA RFA SYSTEM with an ablation tip of 30 mm in length. For the initial lenvatinib administration, 16 patients had an adequate course of treatment and were treated with RFA as add-on therapy (combination group). The other 43 patients were treated by RFA monotherapy (monotherapy group). The popping frequency during RFA was recorded and compared. RESULTS: Popping frequency in the combination group (RFA combined with lenvatinib) was significantly higher than that in the monotherapy group. There was no significant difference between the combination group and the monotherapy group in ablation time, maximum output level, tumour temperature after ablation, or initial resistance value. CONCLUSION: Popping frequency was significantly higher in the combination group. It is possible that the intra-tumour temperature increased rapidly during RFA in the combination group due to the inhibitory effect of lenvatinib on tumour angiogenesis, leading to the occurrence of popping. Further studies are needed to investigate popping after RFA, and precise protocols need to be developed.

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.

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.

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.