Background
To assess the recent real-world changes in the etiologies of liver cirrhosis (LC) in Japan, we conducted a nationwide survey in the annual meeting of the Japan Society of Hepatology (JSH).
...Methods
We investigated the etiologies of LC patients accumulated from 68 participants in 79 institutions (
N
= 48,621). We next assessed changing trends in the etiologies of LC by analyzing cases in which the year of diagnosis was available (
N
= 45,834). We further evaluated the transition in the real number of newly identified LC patients by assessing data from 36 hospitals with complete datasets for 2008–2016 (
N
= 18,358).
Results
In the overall data, HCV infection (48.2%) was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Regarding the transition in the etiologies of LC, the contribution of viral hepatitis-related LC dropped from 73.4 to 49.7%. Among the non-viral etiologies, alcoholic-related disease (ALD) and nonalcoholic steatohepatitis (NASH)-related LC showed a notable increase (from 13.7 to 24.9% and from 2.0 to 9.1%, respectively). Regarding the real numbers of newly diagnosed patients from 2008 to 2016, the numbers of patients with viral hepatitis-related LC decreased, while the numbers of patients with non-viral LC increased.
Conclusions
HCV has remained the main cause of LC in Japan; however, the contribution of viral hepatitis as an etiology of LC is suggested to have been decreasing. In addition, non-viral LC, such as ALD-related LC and NASH-related LC, is suggested to have increased as etiologies of LC in Japan.
Background
We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC).
...Methods
Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (
N
= 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases.
Results
In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased.
Conclusions
Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.
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.
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.
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.
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).
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).
The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.
Summary Background Compared with other countries, patients with chronic hepatitis C infection in Japan tend to be older, have more advanced liver disease, and are more likely to have been previously ...treated for hepatitis C. We aimed to assess the efficacy and safety of an all-oral, fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection. Methods In this randomised, open-label study, we enrolled patients from 19 clinical Japanese centres. Patients were randomly assigned (1:1) to receive either ledipasvir (90 mg) and sofosbuvir (400 mg) or ledipasvir, sofosbuvir, and ribavirin (dosed according to the Japanese Copegus product label—ie, patients ≤60 kg received 600 mg daily, patients >60 kg to ≤80 kg received 800 mg daily, and patients >80 kg received 1000 mg daily) orally once daily for 12 weeks. After completion or early discontinuation of treatment, patients were followed up off-treatment for 24 weeks. Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log10 IU/mL, creatinine clearance of at least 1·0 mL/s, and a platelet count of at least 50 × 109 per L. An interactive web response system was used to manage patient randomisation and treatment assignment. Randomisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category (relapser or breakthrough, non-responder, or interferon-intolerant) for previously treated patients. Within each strata, patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12) assessed in all patients who were randomly assigned and received at least one dose of study drug; safety outcomes were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , number NCT01975675. Findings Between Oct 15, 2013 and Dec 13, 2013, 341 patients were randomly assigned to treatment groups and received at least one dose of study treatment. SVR12 was achieved in all 171 (100%) patients (83 of 83 treatment naive and 88 of 88 treatment experienced) receiving ledipasvir-sofosbuvir (95% CI 98–100) and 167 (98%) of 170 patients (80 of 83 treatment naive and 87 of 87 treatment experienced) receiving ledipasvir-sofosbuvir plus ribavirin (95% CI 95–100). Of the 76 patients with baseline NS5A resistant variants, 75 (99%) achieved SVR12. Two (1·2%) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events. The most common adverse events were nasopharyngitis (50 29·2% of 171), headache (12 7·0% of 171), and malaise (nine 5·3% of 171) in patients receiving ledipasvir-sofosbuvir; and nasopharyngitis (40 23·5% of 170), anaemia (23 13·5% of 170), and headache in those receiving ledipasvir-sofosbuvir and ribavirin (15 8·8% of 170). Interpretation Although existing regimens for the treatment of hepatitis C virus are effective for many patients, medical needs remain unmet, particularly in Japan where the population with hepatitis C virus genotype 1 is generally older and treatment-experienced, with advanced liver disease. The efficacy, tolerability, and absence of drug–drug interactions of ledipasvir-sofosbuvir suggest that it could be an important option for treatment of genotype 1 hepatitis C virus in Japanese patients. Funding Gilead Sciences.
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.
Aim
We aimed to examine the relationship between the Wisteria floribunda agglutinin positive Mac‐2‐binding protein (WFA+‐M2BP) level and high‐sensitivity C‐reactive protein (hCRP) concentration and ...liver histological findings for patients with autoimmune hepatitis (AIH).
Methods
A total of 84 AIH patients (median age, 64 years) were analyzed. We examined the effect of pretreatment WFA+‐M2BP level and hCRP concentration on histological findings of liver fibrosis and liver inflammation activity comparing with other laboratory markers. Receiver–operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC).
Results
The median WFA+‐M2BP values in each fibrosis stage were: 1.5 cut‐off index (COI) in F1, 2.1 in F2, 3.3 in F3 and 9.8 in F4 (P < 0.001). The median WFA+‐M2BP values in each liver inflammation stage were: 1.6 COI in A1, 2.5 in A2 and 5.4 in A3 (P < 0.001). For predicting liver cirrhosis (F4), WFA+‐M2BP yielded the highest AUROC (0.853). For predicting advanced liver fibrosis (F3 or F4), WFA+‐M2BP, FIB‐4 index and hyaluronic acid yielded the highest AUROC (0.747). For predicting severe liver inflammation activity (A3), WFA+‐M2BP yielded the highest AUROC (0.739). The hCRP concentration in patients with A3 (median, 2230 ng/mL) was significantly higher than that in patients with A1 or A2 (median, 854.5 ng/mL) (P < 0.01). WFA+‐M2BP level significantly correlated with hCRP concentration (rs = 0.461, P < 0.001).
Conclusion
WFA+‐M2BP can be a useful marker for assessing liver histological findings in AIH patients and it correlated well with hCRP concentration.
The development of hepatocellular carcinoma (HCC) is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related ...to the progression of HCC. HDGF (hepatoma-derived growth factor) is a novel growth factor that belongs to a new gene family. HDGF was initially purified from the conditioned medium of a hepatoma cell line. HDGF promotes cellular proliferation as a DNA binding nuclear factor and a secreted protein acting via a receptor-mediated pathway. HDGF is a unique multi-functional protein that can function as a growth factor, angiogenic factor and anti-apoptotic factor and it participates in the development and progression of various malignant diseases. The expression level of HDGF may be an independent prognostic factor for predicting the disease-free and overall survival in patients with various malignancies, including HCC. Furthermore, the overexpression of HDGF promotes the proliferation of HCC cells, while a reduction in the HDGF expression inhibits the proliferation of HCC cells. This article provides an overview of the characteristics of HDGF and describes the potential role of HDGF as a growth-promoting factor for HCC.
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