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 effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no ...randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (
p
= 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.
Endoscopic submucosal dissection (ESD) provides strong therapeutic benefits for early gastrointestinal cancer as a minimally invasive treatment. However, there is currently no reliable treatment to ...prevent scar contracture resulting from ESD which may lead to cicatricial stricture. Herein, a multifunctional colloidal wound dressing to promote tissue regeneration after ESD is demonstrated. This sprayable wound dressing, composed of hydrophobized microparticles, exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re‐epithelialization, angiogenesis, and controlled inflammation based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric ESD models reveals that this colloidal wound dressing suppresses fibrosis and accelerates wound healing. Multifunctional colloidal and sprayable wound dressings have an enormous therapeutic potential for use in a wide range of biomedical applications including accelerated wound healing after ESD, prevention of perforation, and the treatment of inflammatory diseases.
A tissue‐adhesive microparticle‐based wound dressing for promoting wound healing after endoscopic surgery is demonstrated. Sprayable dressing of hydrophobized microparticles exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re‐epithelialization, and angiogenesis based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric endoscopic submucosal dissection models reveals suppression of fibrosis and promotion of wound healing.
Aim
To summarize the annual nationwide survey on fulminant hepatitis (FH) and late‐onset hepatic failure (LOHF) between 2004 and 2009 in Japan.
Methods
The annual survey was performed in a two‐step ...questionnaire process to detail the clinical profile and prognosis of patients in special hospitals.
Results
Four hundred and sixty (n = 227 acute type; n = 233 subacute type) patients had FH and 28 patients had LOHF. The mean age of patients with FH and LOHF were 51.1 ± 17.0 and 58.0 ± 14.4 years, respectively. The causes of FH were hepatitis A virus in 3.0%, hepatitis B virus (HBV) in 40.2%, other viruses in 2.0%, autoimmune hepatitis in 8.3%, drug allergy‐induced in 14.6% and indeterminate etiology in 29.6% of patients. HBV reactivation due to immunosuppressive therapy was observed in 6.8% of FH patients. The short‐term survival rates of patients without liver transplantation (LT) were 48.7% and 24.2% for the acute and subacute type, respectively, and 13.0% for LOHF. The prognosis was poor in patients with HBV reactivation. The implementation rate for LT in FH patients was equivalent to that in the previous survey. The short‐term survival rates of total patients, including LT patients, were 54.2% and 40.8% for the acute and subacute type, respectively, and 28.6% for LOHF.
Conclusion
The demographic features and etiology of FH patients has gradually changed. HBV reactivation due to immunosuppressive therapy is problematic. Despite advances in therapeutic approaches, the prognosis of patients without LT has not improved.
With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual ...nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid‐containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.
Background:
Approximately 25% of patients with ulcerative colitis UC experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to ...assess the efficacy of tacrolimus as a rescue therapy for active UC.
Methods:
Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials RCTs and observational studies.
Results:
Two RCTs comparing high trough concentration 10–15ng/ml versus placebo n = 103 and 23 observational studies n = 831 were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio RR = 4.61, 95% confidence interval CI = 2.09–10.17, p = 0.15 x 10-3 among RCTs. Rates of clinical response at 1 and 3 months were 0.73 95% CI = 0.64–0.81 and 0.76 95% CI = 0.59–0.87, and colectomy-free rates remained high at 1, 3, 6, and 12 months 0.86, 0.84, 0.78, and 0.69, respectively among observational studies. Among RCTs, adverse events were more frequent compared with placebo RR = 2.01, 95% CI = 1.20–3.37, p = 0.83 x 10-2, but there was no difference in severe adverse events RR = 3.15, 95% CI = 0.14–72.9, p = 0.47. Severe adverse events were rare among observational studies 0.11, 95% CI = 0.06–0.20.
Conclusions:
In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC.
Background
Metabolic syndrome, which includes obesity, hyperglycemia, dyslipidemia, and hypertension, is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD). Cigarette ...smoking is a well-known risk factor for metabolic syndrome, but the epidemiological impact of cigarette smoking on development of NAFLD is unclear.
Methods
In this retrospective study, 2,029 subjects underwent a complete medical health checkup in 1998 and again in 2008. Those who were positive for hepatitis B surface antigen or hepatitis C virus antibody, or had an alcohol intake of >20 g/day as assessed by questionnaire, were excluded. Fatty liver was diagnosed by abdominal ultrasonography. Independent risk factors associated with the development of NAFLD were determined by multiple logistic regression analysis. Smoking status was expressed using the Brinkman index (BI), which was calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking.
Results
Of 1,560 subjects without NAFLD in 1998, 266 (17.1%) were newly diagnosed with NAFLD in 2008. Multiple logistic analysis identified age adjusted odds ratio (AOR) 0.95, 95% confidence interval (95% CI) 0.94–0.97, male sex (AOR 1.46, 95% CI 1.01–2.10), body mass index ≥25 (AOR 3.08, 95% CI 2.20–4.32), dyslipidemia (AOR 1.79, 95% CI 1.25–2.58) and cigarette smoking (AOR 1.91, 95% CI 1.34–2.72) as risk factors associated with the development of NAFLD. Smoking status at baseline was also associated with the development of NAFLD (BI 1–399: AOR 1.77, 95% CI 1.02–3.07, BI ≥400: AOR 2.04, 95% CI 1.37–3.03).
Conclusion
Cigarette smoking is an independent risk factor for onset of NAFLD.
Background
Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained ...virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1).
Methods
This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m
2
); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR
12
).
Results
The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR
12
was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis.
Conclusions
G/P achieved high SVR
12
rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.
To establish diagnostic criteria for acute‐on‐chronic liver failure (ACLF) in Japan, the Intractable Hepato‐Biliary Disease Study Group of Japan undertook a multicenter pilot survey for patients ...fulfilling the Asian Pacific Association for the Study of the Liver (APASL), Association for the Study of the Liver–Chronic Liver Failure (EASL‐Clif) Consortium, or Chinese Medical Association (CMA) diagnostic criteria for ACLF. The APASL criteria were suitable for screening Japanese patients with ACLF when patients whose conditions were triggered by gastrointestinal bleeding were included within the disease entity, and the EASL‐Clif Consortium criteria were useful for classifying the severity of the patients’ conditions. Based on these observations, the Study Group proposed the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and a Child–Pugh score of 5–9 should be diagnosed as having ACLF when a deterioration of liver function (serum bilirubin level ≥5.0 mg/dL and prothrombin time value ≤40% of the standardized values and/or international normalization rate ≥1.5) caused by severe liver damage develops within 28 days after acute insults, such as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the exacerbation of underlying liver diseases. The severities of the patients can be classified into four grades depending on the extent of the deterioration in organ functions, including kidney, cerebral, blood coagulation, circulatory and respiratory functions, as well as liver function. The usefulness of these novel criteria should be validated prospectively in a large‐scale cohort in the future.
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