Etiological changes of liver cirrhosis and hepatocellular carcinoma-complicated liver cirrhosis in Japan: Updated nationwide survey from 2018 to 2021.

AIM: A nationwide survey in 2018 showed decreasing involvement of viral hepatitis and increasing involvement of nonviral liver diseases in the etiology of liver cirrhosis (LC) in Japan. An updated nationwide survey was undertaken in 2023. METHODS: Cases of LC diagnosed between 2018 and 2021 were collected from 75 institutions, and the etiologies of LC were investigated. In addition, the data obtained were compared with the results of previous studies. RESULTS: Among the 15 517 cases, alcohol-related liver disease (ALD)-associated LC was the most frequent cause (n = 5,487, 35.4%). Hepatitis C virus-associated LC, nonalcoholic steatohepatitis (NASH)-associated LC, and hepatitis B virus-associated LC were ranked as second, third, and fourth, respectively. In comparison to the previous survey, the ratios of viral hepatitis-associated LC decreased (HBV: from 11.5% to 8.1%; HCV: from 48.2% to 23.4%), while the ratios of ALD-associated LC and NASH-associated LC increased (from 19.9% to 35.4% and from 6.3% to 14.6%, respectively). Regarding cases of LC with hepatocellular carcinoma (n = 5906), HCV-associated LC (1986 cases, 33.6%) was the most frequent cause. Alcohol-related liver disease-associated LC, NASH-associated LC, and HBV-associated LC were the second-, third-, and fourth-ranked causes, respectively. In comparison to the previous survey, as the cause of hepatocellular carcinoma-complicated LC, HCV-associated LC decreased from 60.3% to 33.6%, while the ratios of ALD-associated LC and NASH-associated LC increased from 14.2% to 28.6% and from 4.2% to 14.0%, respectively. CONCLUSIONS: The major causes of LC in Japan are suggested to have been shifting from viral hepatitis to nonviral chronic liver diseases.

Metabolic dysfunction-associated steatotic liver disease criteria may underestimate the number of lean female nonalcoholic fatty liver disease patients with significant liver fibrosis.

AIM: It remains unclear whether the newly defined concept of metabolic dysfunction-associated steatotic liver disease (MASLD) appropriately includes patients with nonalcoholic fatty liver disease with significant liver fibrosis. METHODS: A total of 4112 patients in whom nonalcoholic fatty liver disease was diagnosed by ultrasonography during medical checkups were enrolled. We defined a fibrosis-4 index ≥1.3 in patients aged <65 years and ≥2.0 in patients aged ≥65 years as significant liver fibrosis. RESULTS: The numbers of patients with a low, intermediate, and high probability of advanced fibrosis based on the fibrosis-4 index were 3360 (81.7%), 668 (16.2%), and 84 (2.0%). There were 3828 (93.1%) and 284 (6.9%) patients diagnosed with MASLD and non-MASLD. The non-MASLD group, compared with the MASLD group, was significantly younger (44 vs. 55 years) and had a higher percentage of women (62.3% vs. 27.7%). Significant fibrosis, defined based on the fibrosis-4 index, was present in 18.5% of the MASLD group and 15.5% of the non-MASLD group. In a multivariable analysis, female sex (OR 6.170, 95% CI 3.180-12.000; p < 0.001) was independently associated with non-MASLD in patients with a significant fibrosis. Among non-MASLD patients with a significant fibrosis (n = 44), body mass index was significantly lower in females than in males (p < 0.001). In a multivariable analysis of patients aged <65 years, female sex (OR, 7.700; 95% CI, 3.750-15.800; p < 0.001) remained independently associated with non-MASLD in patients with a significant fibrosis. CONCLUSIONS: MASLD may inappropriately exclude patients with significant fibrosis, especially lean females with nonalcoholic fatty liver disease.

A Low Geriatric Nutritional Risk Index Is Associated with Low Muscle Volume and a Poor Prognosis among Cirrhotic Patients.

Background and Objectives: The geriatric nutritional risk index (GNRI) is an easily calculable index that can be determined using three common clinical variables. The GNRI is suggested to be related to sarcopenia in cirrhotic patients. However, the relationship between the GNRI and the prognosis in patients with liver cirrhosis (LC) has not been reported. The aim of the present research is to study the association of the GNRI with the nutritional status, hepatic function reserve, and prognosis in patients with liver cirrhosis (LC). Materials and Methods: A total of 370 cirrhotic patients whose nutritional statuses were evaluated using anthropometric measurements and bioimpedance analysis were studied. The associations between the GNRI and nutritional status and the GNRI and hepatic function reserve were analyzed. We also investigated the GNRI and prognosis of patients with LC. Results: The median age of the enrolled patients was 66 years old, and 266 (71.9%) patients had viral hepatitis-related LC. The GNRI was shown to decrease with the progression of chronic liver disease, represented by an increased FIB-4 index and severe Child-Pugh and mALBI grades. In addition, a low GNRI (<92) was associated with severe cirrhosis-related metabolic disorders, including a low branched-chain amino acid-to-tyrosine ratio (BTR) and a low zinc value. The GNRI was positively correlated with two nutrition-related anthropometric variables (% arm circumference and % arm muscle circumference), and a low GNRI was related to a low skeletal muscle mass index (SMI) (<7.0 kg/m2 for men or <5.7 kg/m2 for women), as determined by using bioimpedance analysis. In addition, patients with a low GNRI (<92) had a poorer prognosis than those with a high GNRI (≥92) (log-rank test: p = 0.0161, and generalized Wilcoxon test, p = 0.01261). Conclusions: Our results suggest that a low GNRI is related to severe chronic liver disease, low muscle volume, and a poor prognosis of patients with cirrhosis.

A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study.

INTRODUCTION: In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD. METHODS: Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285). RESULTS: In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83-0.94) and 0.83 (95% CI: 0.73-0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at -6 and -4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively ( P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80-0.90). DISCUSSION: The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.

Diagnosis of hepatic steatosis based on ultrasound attenuation imaging is not influenced by liver fibrosis.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Attenuation imaging values are not influenced by liver fibrosis.

Outcome of nucleos(t)ide analog intervention in patients with preventive or on-demand therapy for hepatitis B virus reactivation.

Preventive or on-demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV-R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies. We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on-demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml. NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on-demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels <20 IU/ml (preventive group). HBV relapse occurred in five (33%) patients in the on-demand group. Relapse occurred only in anti-HBs-negative patients at the cessation of NA therapy. There were no cases of hepatitis flare after the cessation of NA therapy. HBsAg predicted HBV relapse after the cessation of NA therapy in HBsAg-positive patients. Anti-HBs could be a predictive marker for NA therapy cessation in patients with resolved HBV.

Clinical impact of the finger-circle test in patients with liver diseases.

AIM: To elucidate the relationship between the finger-circle test (Yubi-wakka [in Japanese] test; three levels of bigger, just-fits, and smaller) and sarcopenia-related factors and anthropometric parameters in patients with chronic liver disease (n = 202, 99 men, mean age 61 years). METHODS: Patients with both grip strength decline (<26 kg for men and <18 kg for women) and skeletal muscle index (SMI) decline (<7.0 kg/m2 in men and <5.7 kg/m2 in female) were diagnosed as sarcopenia. RESULTS: Liver cirrhosis was found in 56 patients (27.7%). The proportions of bigger, just-fits, and smaller in liver cirrhosis versus non-liver cirrhosis patients were 51.8%, 21.4%, and 26.8% versus 77.4%, 11.4%, and 8.2% (p < 0.01). The proportions of grip strength decline in patients with bigger, just-fits, and smaller were 12.0% (77/142), 21.2% (7/33), and 40.7% (11/27; overall p < 0.01). The proportions of SMI decline in patients with bigger, just-fits, and smaller were 9.9% (14/142), 45.5% (15/33), and 77.8% (21/27; overall p < 0.01). The proportions of sarcopenia in patients with bigger, just-fits, and smaller were 3.5% (5/142), 18.2% (6/33), and 33.3% (9/27; overall p < 0.01). In both sexes, arm circumference, triceps skinfold thickness, calf circumference, and waist circumference were significantly stratified according to the finger-circle test. In the multivariate analysis, smaller was an independent predictor for SMI decline (p < 0.01, risk ratio 8.188, bigger as a reference), and body mass index was an independent predictor for both SMI decline and sarcopenia. CONCLUSION: The finger-circle test can be helpful for the screening of sarcopenia in chronic liver disease and is closely linked to body composition.

Severity of liver fibrosis using shear wave elastography is influenced by hepatic necroinflammation in chronic hepatitis patients, but not in cirrhotic patients.

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 < 0.001). In patients with F0-1, F2, and F3, TE and VTQ values of A2 or A3 were significantly higher than those of A0 or A1 (p value, all <0.05), but not in patients with F4. The median alanine aminotransferase (ALT) values increased significantly with the progression of liver inflammation (p < 0.001). Moreover, TE and VTQ in patients with ALT ≥70 IU/L were significantly higher than those in patients with ALT <70 IU/L (p < 0.01), but not in patients with F4. CONCLUSION: Shear wave elastography can be affected by hepatic necroinflammation in F0-F3 fibrosis, but not in F4.

Association of liver stiffness and steatosis with hepatocellular carcinoma development in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

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.

Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact.

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle-liver-adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.

Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis.

Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies.

Hepatoma-derived growth factor (HDGF) was identified in research seeking to find a novel growth factor for hepatoma cells. Subsequently, four HDGF-related proteins were identified, and these proteins are considered to be members of a new gene family. HDGF has a growth-stimulating role, an angiogenesis-inducing role, and a probable anti-apoptotic role. HDGF is ubiquitously expressed in non-cancerous tissues, and participates in organ development and in the healing of damaged tissues. In addition, the high expression of HDGF was reported to be closely associated with unfavorable clinical outcomes in several malignant diseases. Thus, HDGF is considered to contribute to the development and progression of malignant disease. We herein provide a brief overview of the factor and its functions in relation to benign and malignant cells. We also describe its possible role as a target molecule for digestive malignancies.

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

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 = 1.0×10-4). 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.

Close Correlation between Frailty and Depressive State in Chronic Liver Diseases.

BACKGROUND AND OBJECTIVES: Few data with regard to the relevance between depression and frailty in chronic liver disease (CLD) patients are currently available. We aimed to elucidate the relationship between frailty and depression as evaluated by the Beck Depression Inventory-2nd edition (BDI-II) in CLD patients (n = 340, median age = 65.0 years). METHODS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were met: body weight loss, exhaustion, muscle weakness, slow walking speed and low physical activity. Depressive state was defined as BDI-II score 11 or greater. RESULTS: Robust (frailty score = zero), prefrail (frailty score = one or two) and frailty were identified in 114 (33.5%), 182 (53.5%) and 44 (12.9%). The median BDI-II score was five. Depressive state was identified in 84 patients (24.7%). The median BDI-II scores in patients with robust, prefrail and frail traits were 2, 7 and 12.5 (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0003; robust vs. frail, p < 0.0001; overall p < 0.0001). The proportions of depressive state in patients with robust, prefrail and frail traits were 3.51%, 30.77% and 54.55% (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0046; robust vs. frail, p < 0.0001; overall p < 0.0001). BDI-II score significantly correlated with frailty score (rs = 0.5855, p < 0.0001). CONCLUSIONS: The close correlation between frailty and depression can be found in CLD. Preventing frailty in CLD should be approached both physiologically and psychologically.

Proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B.

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 < 0.0001, r = 0.67), whereas the FBS-cres score was more closely correlated to IH-cccDNA level (P < 0.0001, r = 0.81). In the validation cohort, significant correlation was found between HBcrAg and IH-cccDNA levels (P = 0.0012, r = 0.38), whereas the FBS-cres score was more closely linked to IH-cccDNA levels (P < 0.0001, r = 0.51). Similar tendencies were observed in all subgroup analyses. CONCLUSION: Our proposed model for the prediction of IH-cccDNA level could be helpful in CHB patients.

Liver fibrosis markers as assessed by ultrasound elastography and serum samples: A large comparative study in hepatitis virus B and C liver diseases.

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 <0.0001). Similar tendencies were noted by F stage-based stratification. The median TCPA in the CHB cohort and the CHC cohort were 8.5% and 12.7% (P < 0.0006). The TCPA values in the CHC cohort were higher than those in the CHB cohort regardless of LF stage. CONCLUSION: Values of LF markers in CHB patients can differ from those in CHC patients even in the same LF stage. Difference in total amount of collagen fiber in CHB and CHC appears to be linked to the difference.

Comparison of liver stiffness assessment by transient elastography and shear wave elastography using six ultrasound devices.

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 < 0.001). Receiver operating characteristic (ROC) curve analysis for predicting significant fibrosis (≥F2) and cirrhosis yielded area under the ROC curve (AUROC) values based on TE of 0.830 (95% confidence interval [CI], 0.755-0.905) and 0.959 (95% CI, 0.924-0.995), respectively. The AUROCs for predicting significant fibrosis (≥F2) and cirrhosis (F4) based on SWE from all five ultrasound devices were over 0.8 and 0.9, respectively. Furthermore, the correlation coefficients between TE values and SWE values from five ultrasound devices were all over 0.8, indicating a strong relationship. CONCLUSION: Our study showed strong correlations between TE and SWEs with high correlation coefficients. The regression equations between TE and SWEs demonstrated the ability to compare the measurement values in each device equivalently.

Sequential therapy involving an early switch from entecavir to pegylated interferon-α in Japanese patients with chronic hepatitis B.

AIM: The optimal combination of two currently available agents with different mechanisms of action, a nucleos(t)ide analog and pegylated interferon-α (PegIFNα), must be determined to improve treatment of chronic hepatitis B (CHB). METHODS: In this study, 24 patients with CHB (14 hepatitis B envelope antigen [HBeAg]-positive patients and 10 HBeAg-negative patients) received entecavir for 36-52 weeks, followed by entecavir plus Peg-IFNα2a for 4 weeks, and finally by PegIFNα-2a alone for 44 weeks. RESULTS: A sustained biochemical, virologic, and serologic response was obtained in 7/24 (29%) patients at 48 weeks post-treatment (2/14 [14%] in HBeAg-positive vs 5/10 [50%] in HBeAg-negative patients, P = 0.085). At baseline, patients with a sustained response had a significantly lower γ-glutamyl transferase level (P = 0.0023), a lower aspartate aminotransferase-to-platelet ratio index (P = 0.049), and a lower α-fetoprotein level (P = 0.042) than those without a sustained response. The decline in hepatitis B surface antigen (HBsAg) levels during the first 24 weeks of PegIFNα-2a treatment in patients with a sustained response was greater than that in patients without (P = 0.017). Additionally, HBsAg seroclearance was achieved in two patients (8.3%): one HBeAg-positive and one HBeAg-negative patient. CONCLUSION: The outcomes of sequential therapy involving an early switch from entecavir to PegIFNα-2a were unsatisfactory in Japanese patients with CHB. In addition to viral factors, host metabolic characteristics and liver fibrosis/tumor markers can be used for prediction of a sustained response to therapy, but accurate prediction of the therapeutic response is difficult.