Background
A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.
Methods
Two-step surveys for patients with ALF ...and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys.
Results
In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation).
Conclusion
Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.
Background
The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated.
Methods
A nationwide survey was performed for patients with ...ACLF occurring between 2017 and 2019. Cirrhotic patients with a Child–Pugh score of 5–9 were diagnosed as having ACLF when liver failure (serum bilirubin level of ≥ 5.0 mg/dL and a prothrombin time international normalization rate INR of ≥ 1.5) occurred within 28 days after an acute insult. Patients who fulfilled either criterion (total serum bilirubin or INR) and/or those with indeterminate Child–Pugh scores at baseline were also enrolled.
Results
Among the 501 enrolled patients, 183 patients (37%) were diagnosed as having ACLF. The etiologies of the cirrhosis and acute insults were alcohol intake/abuse in 114 (62%) and 75 (41%) patients, respectively. Sixty-eight patients (37%) were also diagnosed as having severe alcoholic hepatitis. The survival rate without liver transplantation was 48% among the ACLF patients and 71% in the remaining patients (
P
< 0.01). A multivariate analysis revealed that the disease condition was significantly associated with mortality, with an odds ratio of 2.025 in ACLF patients relative to the remaining patients (
P
< 0.01), and patient age and the number of organs with functional failure were also associated with mortality among the ACLF patients.
Conclusion
The proposed diagnostic criteria for ACLF were useful for identifying cirrhotic patients with an unfavorable outcome following acute insults. A therapeutic strategy for patients with severe alcoholic hepatitis should be established, since such patients accounted for the majority of ACLF patients.
Abstract
Patients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute ...liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836;
P
< 0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832–0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.
Aim
Hepatic encephalopathy (HE) development is crucial in liver transplantation for patients with acute liver injury (ALI) and failure (ALF); to predict HE development, the Japan Hepatic ...Encephalopathy Prediction (JHEP) model, calculated using age, etiology, prothrombin time (PT), and total bilirubin, was established in 2004, and a referral system to the liver center was implemented using the JHEP model from April 2004.
Methods
The JHEP model's ability to predict HE development in 460 consecutive patients with ALI between April 2004 and January 2021 using data from the referral system was evaluated, and the JHEP model was revised.
Results
During the observation period, 7.8% patients developed HE. There was no difference in the proportion of HE development among the etiologies. In the Hosmer–Lemeshow test for HE development prediction, the JHEP model, revised JHEP (rJHEP) model, which was calculated without etiology data, and the modified JHEP model, which used the PT international ratio instead of PT in the rJHEP model, were good fitting models. Upon 30% random sampling from the total patients 60 times, the receiver operating curve analysis of both JHEP and rJHEP models for HE development was performed in all the datasets. The area under the curve of the JHEP model was subtracted from that of the rJHEP model (95% confidential interval, 0.000516–0.01793).
Conclusions
The referral system using the JHEP model reduced the difference in the risk for HE development among each etiology; the rJHEP model had a better prediction ability for HE development than the JHEP model.
Abstract
Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the ...liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance—demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test—and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.
Sarcopenia is a common complication in patients with chronic liver disease (CLD); however, the progression of sarcopenia over the course of CLD is unclear. The present study therefore determined the ...natural course of the progression of sarcopenia in patients with CLD and the effect of liver cirrhosis (LC) on this progression. This observational study analyzed patients with chronic hepatitis (CH) (n = 536) and LC (n = 320) who underwent evaluations of the grip strength and skeletal muscle mass of the arms, trunk, and legs for sarcopenia between 2016 and 2021. A bioelectrical impedance analysis was used to evaluate skeletal muscle mass. The annual rate of change (%/year) in two tests were compared between patients with CH and LC. The annual rates of change in grip strength and skeletal muscle of arms, trunk, and legs of patients with CH and LC were - 0.84% vs. - 2.93%, - 0.54% vs. - 1.71%, - 0.43% vs. - 1.02%, and - 0.76% vs. - 1.70% for men and - 0.12% vs. - 1.71%, - 0.66% vs. - 1.71%, - 0.49% vs. - 1.31%, and - 0.76% vs. - 1.54% for women, respectively. The progression of sarcopenia was greater in LC patients than in CH patients and that the decrease in grip strength was most prominent in the progression of sarcopenia in patients with LC.
Sarcopenia is associated with poor prognosis of patients with hepatocellular carcinoma (HCC). We investigated the association of skeletal muscle volume (SMV) and its change in HCC patients taking ...lenvatinib. In 130 HCC patients, psoas mass index (PMI) was calculated as the left-right sum of the major × minor axis of psoas muscle at the third lumbar vertebra, divided by height squared. Patients were classified into two groups (low and normal PMI) based on indices of < 6.0 cm
/m
for man and < 3.4 cm
/m
for women. Change in PMI per month during the lenvatinib administration period (ΔPMI/m) was calculated; and patients were classified into two groups (severe and mild atrophy) based on the ΔPMI/m rate, as ≥ 1% or < 1%, respectively. There was no significant difference in Overall survival (OS) between the low and normal PMI groups at the start of lenvatinib administration. OS was significantly lower in the severe atrophy group than in the mild atrophy group (median; 15.2 vs. 25.6 months, P = 0.005). Multivariate analysis revealed a significant association of severe atrophy with OS (hazard ratio 1.927, P = 0.031). Progressive loss of SMV is a strong predictor of poor prognosis in HCC patients taking lenvatinib.
We investigated the usefulness of combining two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter for assessing the risk of progressive non-alcoholic ...steatohepatitis, defined as non-alcoholic steatohepatitis with a non-alcoholic fatty liver disease activity score of ≥4 and a fibrosis stage of ≥2.
This prospective study included 202 patients with non-alcoholic fatty liver disease who underwent two-dimensional shear wave elastography, ultrasound-guided attenuation parameter, vibration-controlled transient elastography, the controlled attenuation parameter, and liver biopsy on the same day. Patients were grouped according to liver stiffness measurement using two-dimensional shear wave elastography and the attenuation coefficient, assessed using the ultrasound-guided attenuation parameter: A, low liver stiffness measurement/low attenuation coefficient; B, low liver stiffness measurement/high attenuation coefficient; C, high liver stiffness measurement/low attenuation coefficient; and D, high liver stiffness measurement/high attenuation coefficient.
Two-dimensional shear wave elastography and vibration-controlled transient elastography had equivalent diagnostic performance for fibrosis. The areas under the curve of the ultrasound-guided attenuation parameter for identifying steatosis grades ≥S1, ≥S2, and S3 were 0.89, 0.91, and 0.92, respectively, which were significantly better than those of the controlled attenuation parameter (P<0.05). The percentages of progressive non-alcoholic steatohepatitis in Groups A, B, C, and D were 0.0%, 7.7%, 35.7%, and 50.0%, respectively (P<0.001). The prediction model was established as logit (p) = 0.5414 × liver stiffness measurement (kPa) + 7.791 × attenuation coefficient (dB/cm/MHz)-8.401, with area under the receiver operating characteristic curve, sensitivity, and specificity values of 0.832, 80.9%, and 74.6%, respectively; there was no significant difference from the FibroScan-aspartate aminotransferase score.
Combined assessment by two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter is useful for risk stratification of progressive non-alcoholic steatohepatitis and may be convenient for evaluating the necessity of specialist referral and liver biopsy.
Liver tests (LT), especially to measure AST, ALT and GGT levels, are widely used to evaluate the risk of alcohol-related liver disease (ALD). In this study, we investigated the potential genetic ...factors that modulate the association between LTs and alcohol consumption. We conducted a genome-wide interaction meta-analysis in 7856 Japanese subjects from Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) study recruited in 2013, and identified 2 loci (12q24 and 2p16) with genome-wide significance (P > 5 × 10
). The significant variants in the 12q24 included rs671, a variant associated with alcohol intolerance and located at a coding exon of ALDH2. We found that the amount of alcohol consumption was associated with increased level AST/ALT ratio among the subjects with the rs671 GA genotype. The elevated AST/ALT ratio among subjects with moderate-to-high levels of drinking behavior and the rs671 GA genotype was due to decreased levels of ALT, which was not accompanied with significant differences in AST levels. Although the interaction effect was significant in both men and women, the effect was much larger in men. Our results suggest that the impact of alcohol consumption on LT varies according to the ALDH2 genotype, providing an insight for the accurate screening of ALD in drinkers with the rs671 GA genotype.
Background
The aim of the present study was to examine the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) based on the long‐term outcomes.
Patients and ...Methods
From June 2002 to March 2007, ESD was carried out in 472 cases and 570 lesions of EGC. Post‐surgical cases and status‐unknown cases were excluded. The following long‐term outcomes were examined in 438 patients who were reliably followed up for at least 5 years after treatment (range: 5 years 60 months to 9 years, 9 months 117 months): local recurrence, metachronous recurrences, and the survival rate.
Results
The overall en bloc resection rate was 97.7% for all lesions treated by ESD. The median procedure time was 47.0 min (range 8–345 min). The incidence of positive horizontal andvertical margins was 3.7% and 3.4%, respectively. The incidence of perforation and postoperative bleeding was 5.3% and 4.3%, respectively. There were no deaths related to ESD. Local recurrence was observed in five patients (1.1%), and metachronous recurrences in 7.8% of the patients. The post‐treatment 5‐year survival was 83.1%. There were no deaths as a result of gastric cancer associated with sites treated by ESD.
Conclusion
ESD can be considered a standard treatment for EGC based on its expanded indications and low incidences of local recurrence and lymph node metastasis.
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