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.
Background
Accurately evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) is important for identifying those who may develop complications. The aims of this study ...were (1) to measure serum
Wisteria floribunda
agglutinin-positive Mac-2 binding protein (WFA
+
-M2BP) using the glycan sugar chain-based immunoassay and (2) to compare the results with clinical assessments of fibrosis.
Methods
Serum WFA
+
-M2BP values were retrospectively evaluated in 289 patients with NAFLD who had undergone liver biopsy. Histological findings were evaluated by three blinded, experienced liver-specific pathologists.
Results
For stages 0 (
n
= 35), 1 (
n
= 113), 2 (
n
= 49), 3 (
n
= 41), and 4 (
n
= 51) of liver fibrosis, the serum WFA
+
-M2BP cutoff indexes were 0.57, 0.70, 1.02, 1.57, and 2.96, respectively. Multivariate regression analysis showed that serum WFA
+
-M2BP values were associated with the stage of fibrosis (≥stage 2). The areas under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum WFA
+
-M2BP were 0.876, 85.9, and 74.6 %, respectively, for severe fibrosis (≥stage 3) and were 0.879, 74.6, and 87.0 %, respectively, for cirrhosis. When compared with six non-invasive conventional markers, serum WFA
+
-M2BP had the greatest AUROC for diagnosing severe fibrosis and cirrhosis.
Conclusions
Serum WFA
+
-M2BP values are useful for assessing the stage of liver fibrosis in patients with NAFLD.
In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the ...molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.
Background
Even though both interferon (IFN)-based and direct-acting antiviral (DAA) therapies against hepatitis C virus (HCV) reduce the risk of hepatocellular carcinoma (HCC), post-sustained ...virological response (SVR) patients remain at elevated risk of HCC.
Methods
A total of 4620 patients who achieved SVR were enrolled in this retrospective cohort study. After excluding patients who had a history of HCC or developed HCC within 1 year and whose follow-up period was less than 1 year and who were positive for HBsAg, we investigated the association between clinical characteristics and HCC development after SVR in the remaining 3771 patients.
Results
Median observation period was 41 months. We confirmed known risk factors. In addition, we found that
PNPLA3
and
HLA-DQB1
polymorphisms were associated with HCC after SVR. Finally, we propose an estimation model for the incidence of HCC after SVR. Based on gender, FIB-4 index, AFP, and
PNPLA3
polymorphism, about 18% of all patients were classified as having high risk, with a cumulative incidence rate (CIR) at 5 years of 16.5%. Another 17% were classified as having moderate risk with a CIR of 7.6%. The remaining 65% showed a CIR of 0.5%. The effect of
PNPLA3
polymorphism might be more pronounced in patients with lower body mass index (BMI) and without diabetes mellitus compared to those with higher BMI and diabetes mellitus.
Conclusions
We demonstrated that
PNPLA3
and
HLA-DQB1
polymorphisms were associated with HCC after SVR. These findings might be useful to inform risk stratification for HCC surveillance after SVR.
Objective This study evaluated the efficacy associated with switching to rifaximin in patients with hepatic cirrhosis receiving kanamycin sulfate for the treatment of hepatic encephalopathy and ...hyperammonemia. Methods We included 37 patients who switched from kanamycin sulfate to rifaximin at our institution from January 2017 to December 2018. The onset of hepatic encephalopathy and changes in blood ammonia values during a six-month period were retrospectively evaluated. Results There were 4 (11%) patients with hepatic encephalopathy at the time of switching from kanamycin sulfate to rifaximin. The cumulative incidence of hepatic encephalopathy was 3% and 16% at 3 and 6 months later, respectively. The blood ammonia levels at the time of switching to rifaximin and at 3 and 6 months later were 94 (range, 20-243) μg/dL, 95 (range, 33-176) μg/dL, and 81 (range, 32-209) μg/dL, respectively, and no significant changes were observed. However, in the 11 patients receiving an oral dose of <1,500 mg/day of kanamycin sulfate, the blood ammonia levels at the time of switching and at 3 and 6 months later were 136 (range, 35-243) μg/dL, 95 (range, 33-150) μg/dL, and 63 (range, 43-124) μg/dL, respectively. Furthermore, the blood ammonia levels significantly decreased at the time of the switching to rifaximin and at three and six months later (p=0.043 and p=0.011, respectively). Conclusion Switching to rifaximin in hepatic cirrhosis patients receiving kanamycin sulfate to treat hepatic encephalopathy and hyperammonemia showed effects that were equivalent to or greater than the original therapy, thereby demonstrating the clinical efficacy.
Background
Intrahepatic and extrahepatic recurrence remains a significant problem for hepatocellular carcinoma (HCC). The aim of this study was to determine the usefulness of diffusion-weighted ...magnetic resonance imaging (DWI) for histological tumor grading and preoperative prediction of early HCC recurrence within 6 months of operation.
Methods
A total of 44 patients who had undergone hepatic resection for HCC (50 nodules) were reviewed retrospectively. DWI was performed within 30 days before hepatectomy, and apparent diffusion coefficients (ADCs) were measured using 2 methods: mean ADC and minimum-spot ADC. Relationships between ADCs and histological differentiation and between ADCs and early recurrence of HCC were analyzed.
Results
Mean ADC was significantly lower in poorly differentiated HCC (
n
= 18, 1.07 ± 0.15 × 10
−3
mm
2
/s) than in moderately differentiated HCC (
n
= 29, 1.29 ± 0.21 × 10
−3
mm
2
/s;
P
< .05). Minimum-spot ADC was significantly lower in poorly differentiated HCC (
n
= 18, 0.69 ± 0.19 × 10
−3
mm
2
/s) than in well-differentiated HCC (
n
= 3, 1.15 ± 0.10 × 10
−3
mm
2
;
P
< .01) or in moderately differentiated HCC (
n
= 29, 0.98 ± 0.18 × 10
−3
mm
2
/s;
P
< .0001). Of 34 patients who were able to be observed for >6 months after resection, 9 showed early recurrence. Minimum-spot ADC was significantly lower in patients with early recurrence (
n
= 9, 0.64 ± 0.24 × 10
−3
mm
2
/s) than in patients without early recurrence (
n
= 25, 0.88 ± 0.19 × 10
−3
mm
2
/s;
P
< .05). On multivariate analysis, minimum-spot ADC was a significant risk factor for early recurrence (
P
< .05).
Conclusion
Quantitative measurement of ADC of HCC with magnetic resonance diffusion weighted imaging is a promising functional imaging tool in the prediction of histological grade and early recurrence before treatment.
Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive ...carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta) = 1.89×10⁻¹² for rs3077 and P(meta) = 9.69×10⁻¹⁰ for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P(meta) = 4.40×10⁻¹⁹ for rs3077 and P(meta) = 1.28×10⁻¹⁵ for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.
Aim
Cell‐free and concentrated ascites reinfusion therapy (CART) and large‐volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear ...which therapy is more effective in patients with cirrhosis with RA.
Methods
From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8‐week observation period.
Results
Among all patients at entry (median age, 63 years; 52% men; 60% Child–Pugh B and 40% Child–Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health‐related quality of life (HRQOL) and prominent ascites‐related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP.
Conclusions
CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis.
Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is ...different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index.
Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45–3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis.
Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index.
Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.
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