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Recently, a new technique using attenuation imaging (ATI) was developed to diagnose hepatic steatosis. The aim of this study was to investigate whether ATI for the evaluation of hepatic steatosis is influenced by liver fibrosis.A total of 328 patients with chronic liver disease were enrolled to study the associations between histological hepatic steatosis or liver fibrosis and ATI findings. The interaction between liver fibrosis and ATI was also analyzed.Median ATI values according to steatosis grade and fibrosis stage increased in line with the progression of liver steatosis (p 0.001) and fibrosis (p 0.05). However, in each steatosis grade, ATI values according to fibrosis stage were not significantly increased. In multiple regression analyses for assessment of the effect of their interaction, the p values for fibrosis stage, steatosis grade, and fibrosis stage × steatosis grade were 0.096,0.001, and 0.077, respectively. Variance inflation factor values for fibrosis stage, steatosis grade, and fibrosis stage × steatosis grade were 1.079, 1.094, and 1.074, respectively.Attenuation imaging values are not influenced by liver fibrosis.

河村博教授 古稀記念論集, Dedicated to Professor Hiroshi Kawamura on his 70th birthday, Article

Background/Aim: A new scoring system [albumin-bilirubin-platelet (ALBI-PLT) score] was reported for identifying cirrhotic patients without high-risk varices (HRV), and patients with ALBI grade 1 (≤−2.60) and a platelet count over 150×10(9)/l were shown to have a low risk of having HRV. The present study modified the cut-off values of the variables in the ALBI-PLT score. Patients and Methods: Among a total of 338 patients with chronic liver diseases, possible cut-off values of the ALBI score and the platelet count were determined by analyzing the first-half group (training cohort: N=169) with the receiver operating characteristic (ROC) method. The utility of the determined values was evaluated in the second-half group (validation cohort: N=169) and total cohort (N=338). In addition, the utility of the modified cut-off values was evaluated in patients with compensated cirrhosis (cirrhotic cohort: N=87). Results: Possible cut-off values of the ALBI score and platelet count were found to be –2.36 and 114×10(9)/l, respectively. In the training cohort, these cut-off values provided a higher ratio of avoiding esophagogastroduodenoscopy than the original ALBI-PLT score (53.3% vs. 25.4%, p

In recent years, it has become possible to experience sports in the virtual reality (VR) space. Although many haptic displays in the VR environment currently use vibrators as the mainstream, the vibrators’ presentation is not suitable to express ball-receiving in the VR sports experience. Therefore, we have developed a novel haptic display that reproduces an impulsive force by instantaneously applying traction to the palm using a string and wearable brake system. This paper proposes a method to present various reaction forces by dynamic control of the braking system and report the quantitative evaluation of the device’s physical and psychological usability.

Background The causal relationship between sarcopenia and depression in chronic liver disease (CLD) patients is unclear. To elucidate these issues, we aimed to investigate the impacts of muscle strength as assessed by grip strength (GS) and muscle mass as assessed by bioelectrical impedance analysis (BIA) on the progression of depression in CLD patients (n=189, 49 cirrhotic cases, and 87 males). Methods The Beck Depression Inventory-2nd edition (BDI-II) was used for the evaluation of depression. Time interval from the date of baseline BDI-II and the first confirmed date of elevation of BDI-II score was calculated in each subject. We analyzed factors associated with the elevation of BDI-II score. Results The baseline mean BDI-II score was 8.4 (median value, 7). Depression (BDI-II score >11) was found in 63 patients (33.33%). GS decline at baseline was found in 13 male patients (14.9%) and 37 female patients (36.3%). Skeletal muscle index (SMI) by BIA decline at baseline was found in 25 male patients (28.7%) and 40 female patients (39.2%). During the follow-up period, 84 patients (44.4%) had the elevation of BDIII score. For all cases, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 39.2%, 46.6% and 54.9%. In patients with GS decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 53.1%, 67.8% and 77.9%, while in patients with GS non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 34.4%, 39.8% and 47.4% (P=0.0006). In patients with SMI decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 43.5%, 50.8% and 62.1%, while in patients with SMI non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 36.9%, 44.5% and 51.0% (P=0.2487). As per the multivariate analyses, only lower GS at baseline (P=0.0022) was identified to be a significant factor associated with the elevation of BDI-II score. Conclusions Reduced GS rather than loss of muscle mass can be independently associated with an elevated risk for the progression of depression.

川本哲郎教授 奥村正雄教授 古江頼隆教授 古稀記念論集 第二部, Dedicated to Professor Tetsuro Kawamoto Professor Masao Okumura Professor Yoritaka Furue on their 70th birthday, Article

AIM Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically. METHODS A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically. RESULTS The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p

Background/Aim: To elucidate factors associated with secular changes of grip strength (GS) in patients with chronic liver diseases (CLDs) (n=241, 102 males, median age=63 years, 87 liver cirrhosis cases). Materials and Methods: ΔGS (kg/year) was defined as [GS value (second time) – GS value (first time)]/[time interval between the first and second time]. GS loss (GSL) was defined as ΔGS

Background/Aim: Recent advances in antiviral treatment have achieved a sustained viral response (SVR) in over 95% of hepatitis C virus (HCV) infections. HCV elimination is suggested to improve several lifestyle-related factors; however, few studies have focused on dietary habit-/appetite-related factors. Patients and Methods: HCV-infected patients who received Daclatasvir/Asnaprevir (DCV/ASV) therapy were enrolled, and the changes in appetite-related molecules after antiviral therapy were assessed with a multiple cytokine-measuring system. Results: Among 119 HCV-infected patients who received DCV/ASV treatment, 104 (87.3%) achieved an SVR. In the SVR group, DCV/ASV treatment improved several liver-related variables at 24 weeks after the completion of therapy. In patients with an SVR, the values of glucagon-like peptide 1 (GLP-1) and leptin were significantly increased at 24 weeks after completing direct-acting antiviral therapy. However, no significant change was observed in non-SVR patients, regardless of the receipt of direct-acting antiviral treatment. Conclusion: Gastrointestinal hormones related to the dietary habit and/or appetite may be influenced by HCV elimination.

Aim To elucidate the common and different points between sarcopenia and frailty in chronic liver damage (CLD). Patients and methods Patients with both grip strength decline and skeletal muscle index decline were regarded as sarcopenia. Frailty was defined as a syndrome in which 3 or more of the following criteria were met: i) exhaustion, ii) body weight loss, iii) slow walking speed, iv) muscle weakness, and v) low physical activity. Results Sarcopenia and frailty were identified in 52 patients (15.2%) and 46 (13.5%), respectively. The prevalence of sarcopenia and frailty was well stratified according to age and the liver cirrhosis (LC) status. In the multivariate analysis, we identified significant factors for sarcopenia: i) age, ii) LC, iii) body mass index and iv) extracellular water (ECW) to total body water (TBW) ratio, while only the ECW to TBW ratio was significant for frailty. Conclusion Sarcopenia and frailty in CLD should be separately evaluated.

AIM We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all

AIM Transient elastography (TE) is the gold standard for measurement of liver stiffness. The usefulness of shear wave elastographies (SWE) is well accepted. However, the measurement values cannot be equivalently compared because cut-off values for the diagnosis of liver fibrosis are different among those devices. We aimed to clarify correlations, to generate the regression equations between TE and SWEs, and to compare the diagnostic ability of each device to diagnose liver fibrosis. METHODS A total of 109 patients with chronic liver disease who underwent liver biopsy and same-day evaluation of liver stiffness using six ultrasound devices were analyzed. The diagnostic ability of liver stiffness from each ultrasound device and correlations between TE and each SWE were analyzed. RESULTS Liver stiffness measured by all six ultrasound devices increased significantly as liver fibrosis stage advanced (P

AIM The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with chronic hepatitis C virus who receive direct-acting antiviral therapy and achieve sustained virological response. This study investigated two risk factors for HCC in these patients; specifically, hepatic fibrosis and steatosis. METHODS A total of 355 patients in whom hepatitis C virus was eradicated by direct-acting antiviral were evaluated. Fibrosis and steatosis were assessed using transient elastography (TE) and the controlled attenuation parameter (CAP). Inverse probability weighting was applied to patient age, sex, albumin-bilirubin, α-fetoprotein, history of HCC, TE, or CAP. RESULTS The 12-, 24-, and 36-month cumulative incidence rates of HCC were 0.9%, 2.4%, and 4.1%, respectively. Univariate analysis with the Cox proportional hazards model showed that whereas a high TE value (≥10 kPa) was significantly associated with HCC development (HR 7.861, 95% CI 2.126-29.070; p = 0.002), CAP was not. Additionally, univariate analysis with the Cox proportional hazards model adjusted by inverse probability weighting showed that a high TE value was significantly associated with HCC development (HR 3.980, 95% CI, 1.036-15.290; p = 0.044), whereas CAP was not. The cumulative inverse probability weighting-adjusted incidence of HCC rates at 12, 24, and 36 months were 0.0%, 0.5%, and 1.7%, respectively, in patients with a low TE value, and 2.5%, 5.1%, and 7.6%, respectively, in those with a high TE value. CONCLUSION A high TE value was a risk factor for HCC in hepatitis C virus patients who received direct-acting antiviral therapy and achieved sustained virological response.

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.

Background/Aim: To elucidate the influence of calf circumference (CC) on sarcopenia in patients with chronic liver damages (CLDs, n=525, 255 men). Patients and Methods: Anthropometry parameters including arm circumference, arm muscle circumference, CC, arm muscle area, triceps skinfold thickness, waist circumference and body mass index were measured. Patients with both grip strength (GS) decline and skeletal muscle index (SMI) decline were diagnosed as sarcopenic. Results: Liver cirrhosis was identified in 103 cases (40.4%) in males and 87 cases (32.2%) in females. Sarcopenia was identified in 23 male patients (9.0%) and 38 female patients (14.1%). CC had the strong positive correlation with SMI both in male (r=0.79, p

We sought to examine the serum zinc (Zn) level and frailty in patients with chronic liver diseases (CLDs, n = 285, 107 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: &lt, 26 kg in men and &lt, 18 kg in women), slow walking speed (&lt, 1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 90 (31.6%), 157 (55.1%), and 38 (13.3%), respectively. The median serum Zn levels in patients with frailty, prefrailty, and robust were 59.7 &mu, g/dL, 72.8 &mu, g/dL, and 76.9 &mu, g/dL, respectively (p-values: frailty vs. prefrail, p &lt, 0.0001, prefrail vs. robust, p = 0.0063, frailty vs. robust, p &lt, overall p &lt, 0.0001). For all cases, variables with absolute values of correlation coefficient with frailty score (0&ndash, 5) &ge, 0.3 were age (rs = 0.3570, p &lt, 0.0001), serum albumin (rs = &minus, 0.3212, p &lt, 0.0001), extracellular water to total body water ratio using bioimpedance analysis (rs = 0.4386, p &lt, 0.0001), and serum Zn level (rs = &minus, 0.3406, p &lt, 0.0001). In conclusion, decreased serum Zn level in patients with CLDs can be closely associated with the presence of frailty.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409), transmembrane 6 superfamily member 2 (TM6SF2, rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13, rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7, rs641738) and glucokinase regulatory protein (GCKR, rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy, n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0&times, 10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

We aimed to clarify the impact of the serum zinc (Zn) level grading system proposed by the Japanese society of clinical nutrition (JSCN: 80 &mu, g/dL &lt, serum Zn level &lt, 130 &mu, g/dL (type A), 60 &mu, 80 &mu, g/dL (type B), and serum Zn level &lt, 60 &mu, g/dL (type C)) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC) on the incidence of composite hepatic events (Com-HEs) compared with Child&ndash, Pugh (C&ndash, P) classification or albumin-bilirubin (ALBI) grade. (n = 275, median age = 67 years). The Akaike information criterion (AIC) was compared among three prognostic models. Factors associated with the incidence of Com-HEs were also studied. The first incidence of any HE was confirmed in 112 patients (40.7%). The AIC value for Com-HEs by the Zn level grading system was the lowest among the three prognostic models (AIC: 301.788 in Zn level grading system, 303.372 in ALBI grade, and 333.953 in C&ndash, P classification). In the multivariate analysis, male (p = 0.0031), ALBI grade 3 (p = 0.0041), type B (p = 0.0238), type C (p = 0.0004), and persistent viremia (p &lt, 0.0001) were significant factors associated with the incidence of Com-HEs. In conclusion, the serum Zn level grading system proposed by JSCN can be helpful for estimating the incidence of Com-HEs in HCV-related LC patients.

The indications for immune checkpoint inhibitors (ICIs) have expanded to include carcinomas of various organs. However, as ICI therapy expands, the management of immune-related adverse events (irAEs) has become a problem. ICI-related pancreatitis and cholangitis are relatively rare irAEs. Although some patients with ICI-related pancreatitis and cholangitis are asymptomatic and do not require treatment, there have been reports of patients who did not respond to immunosuppressive therapy and died. Thus, the pathogenesis of ICI-related pancreatitis and cholangitis should be clarified immediately. Currently, the role of endoscopy in the diagnosis and treatment of inflammatory pancreatic and biliary duct diseases is becoming increasingly important. In this review, we summarize clinical characteristics as well as radiographic and endoscopic findings of ICI-related pancreatitis and cholangitis.

AIM We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy. METHODS Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n = 57), and those who received previous NA therapy were assigned to the validation cohort (n = 69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA levels was constructed. Next, the reproducibility of that formula was assessed. RESULTS In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P = 0.0227), hepatitis B e antigen (HBeAg) (P = 0.0067) and log10 (HB surface antigen [HBsAg]) (P = 0.0497) were significant, whereas HB core-related antigen (HBcrAg) tended to be significant (P = 0.0562). The formula was constructed and named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg, and HBsAg). The FBS-cres score was calculated as: 3.1686 - (0.0148 × FBS) + (0.1982 × HBcrAg) + (0.0008168 × HBeAg) + (0.1761 × log10 (HBsAg)). In the training cohort, a significant correlation was noted between HBcrAg and IH-cccDNA levels (P

Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy.A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48).Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020).Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.

Background We aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC). Methods A total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm2/m2). The study cohort was divided into two groups based on the median myostatin value in each gender. Results Our study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4–12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4–8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child–Pugh A patients (n = 123) was 2726.0 pg/mL (578.4–12667.2 pg/mL), whereas that for Child–Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3–12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1-, 3-, 5-, and 7-year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high-myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low-myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1-, 3-, 5-, and 7-year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high-myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low-myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (P

We sought to clarify the correlation between non-protein respiratory quotient (npRQ) in indirect calorimetry and serum zinc (Zn) level in chronic liver diseases (CLDs, n = 586, 309 liver cirrhosis (LC) patients, median age = 63 years). Clinical parameters potentially linked to npRQ &lt, 0.85 (best cutoff point for the prognosis in LC patients) were also examined in receiver operating characteristic curve (ROC) analyses. The median npRQ was 0.86. The median serum Zn level was 64 &mu, g/dL. The median npRQ in patients with non-LC, Child&ndash, Pugh A, Child&ndash, Pugh B and Child&ndash, Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p &lt, 0.0001)). The median serum Zn level in patients with npRQ &lt, 0.85 (58 &mu, g/dL) was significantly lower than that in patients with npRQ &ge, 0.85 (68 &mu, g/dL) (p &lt, 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p &lt, 0.0001). Similar tendencies were observed in all subgroup analyses. The highest correlation coefficient between serum Zn level and npRQ was found in patients with Child&ndash, Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ &lt, 0.85, serum Zn level had the highest area under the ROC (AUC) among baseline laboratory parameters (AUC = 0.69). In conclusion, serum Zn level can be helpful for npRQ in patients with CLDs.