Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness ...against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.
The main causes of liver cirrhosis have changed over the past decade. In Japan, the number of deceased donors is increasing but is still insufficient relative to the number of patients awaiting a ...liver transplant. In the present study we aimed to assess the outcomes of candidates for liver transplantation.
This was a retrospective study of adult patients who visited our department for consultation regarding liver transplantation from January 2009 to December 2020. Of a total of 601 patients, 336 were followed-up. The following data were collected and analyzed: patient's characteristics, liver etiology, Child-Pugh and MELD scores, and the eventual outcome, that is, whether liver transplantation was performed.
Only 153 of 336 (45.5%) patients underwent liver transplantation, of which 42 (27.5%) received deceased donor liver transplantation, and 129 (38.4%) died without transplantation. The proportion of patients who underwent liver transplantation was low among patients with nonalcoholic steatohepatitis (NASH) (10.7%) (P < .001). The rate of qualified living donors was the lowest for patients with NASH (28.6%) and that for the other etiologies ranged from 55.6% to 67.4% (P = .050).
Patients with liver cirrhosis due to NASH may have a lesser chance of undergoing liver transplantation from both living and deceased donors.
Health-related quality of life is impaired in patients with autoimmune hepatitis, but the association between health-related quality of life and patients' backgrounds remains unknown. We assessed ...health-related quality of life in patients with autoimmune hepatitis and identified factors associated with its impairment.
We assessed health-related quality of life in patients with autoimmune hepatitis, patients with chronic hepatitis C, and healthy subjects using the Japanese version of the Chronic Liver Disease Questionnaire and the 36-Item Short Form Survey. We compared health-related quality of life in patients with autoimmune hepatitis with that of patients with chronic hepatitis C and healthy subjects.
A total of 265 patients with autoimmune hepatitis, 88 patients with chronic hepatitis C, and 97 healthy subjects were enrolled; most patients were women. The median ages of patients were 65, 66, and 57 years, respectively. Of these patients with autoimmune hepatitis, 10.6% and 57.0% had cirrhosis and comorbid diseases, respectively. The overall Chronic Liver Disease Questionnaire scores (5.5 vs. 6.2, P < 0.001) and physical (48.1 vs. 54.2, P < 0.001) and mental (51.8 vs. 55.0, P = 0.004) component summaries of 36-Item Short Form Survey were significantly lower in patients with autoimmune hepatitis than in healthy subjects, and similar to scores in patients with chronic hepatitis C. Having cirrhosis, comorbid diseases, and treatment for autoimmune hepatitis were associated with impaired health-related quality of life among patients with autoimmune hepatitis. In particular, prednisolone use was associated with lower scores on the worry domain of the Chronic Liver Disease Questionnaire.
Patients with autoimmune hepatitis showed impairment in health-related quality of life, which was associated with not only disease progression, but also comorbid diseases and treatment. Ways to improve health-related quality of life should be considered in patients with AIH when disease outcome is not favorable and when using prednisolone.
Aim
Some autoimmune hepatitis (AIH) patients experience relapse during their clinical course, and some risk factors for relapse have been identified previously using a relatively small sample size. ...The aim of the present study was to identify the risk factors for relapse in recently diagnosed AIH patients using a nationwide survey in Japan.
Methods
The nationwide survey performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017 was re‐evaluated. A total of 614 patients who received corticosteroids were enrolled in the present study. Associations between relapse and patients' characteristics at diagnosis were evaluated using logistic regression analysis.
Results
Relapse was identified in 143 (23.3%) patients after remission. At the time of diagnosis of the disease, there were significant differences in the γ‐glutamyl transpeptidase (γ‐GTP) level, prevalence of liver cirrhosis, and degree of liver fibrosis. Multivariable logistic regression analysis showed that γ‐GTP elevation and liver cirrhosis were significantly associated with relapse.
Conclusion
The γ‐GTP level at diagnosis could help identify AIH patients at higher risk of relapse.
Histopathology is essential for the diagnosis and evaluation of disease activity of autoimmune hepatitis (AIH). We aimed to elucidate the characteristics of AIH from the localization of inflammation. ...We re-evaluated a nationwide survey that was performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017. A total of 303 patients were enrolled, and the clinical and treatment characteristics were compared between the patients with predominantly portal inflammation (230 patients) or lobular inflammation (73 patients). AIH patients with lobular inflammation had a higher probability of being diagnosed with acute hepatitis than those with portal inflammation. Liver enzyme levels were higher in patients with lobular inflammation, whereas immunoglobulin G levels were higher in patients with portal inflammation. The prevalence of an alanine aminotransferase level < 30 U/L after 6 months of treatment was significantly higher in patients with lobular inflammation than in those with portal inflammation (81.7% vs. 67.3%,
P
= 0.046). The localization of inflammation may be useful for evaluating the onset of AIH.
Cytotoxic CD4
T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, ...including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4
T cells express CD8αα
and reside in the intestine (mouse CD4
CTLs; mCD4-CTLs). The population of cytotoxic CD4
T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4
T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4
T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4
CD8A
T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4
CD8A
T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4
CD8A
T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4
CD8A
T cells among the total CD4
T cells in the inflamed intestine of the patients with Crohn's disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4
CD8
T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.
The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9
inflammatory Mφs ...play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9
Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11b
F4/80
hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9
Mφs were firmly replaced by donors, indicating that CCR9
Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU
CCR9
Mφs with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b
cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury.
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