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Background: Corticosteroid (CS) has been introduced in most acute liver failure (ALF) patients for the purpose of suppressing pro-inflammatory cytokines in Japan where a shortage of donor livers exists, whereas CS use is evaluated to be no benefit in Western countries. In the present study, we aimed to clarify the association between infectious complications and CS use in ALF, and determine when to evaluate treatment response and consider the timing for switching to liver transplantation (LT)., Methods: Corticosteroid was administered to patients in the early stage prospectively. Clinical and biochemical features of 110 adult patients were analyzed., Results: Corticosteroids were administered to 78 (71%) patients. The duration between start of CS and onset of infection was 17 ± 10 days. Multivariate analysis revealed that infection was associated with age >50 years (P = 0.034) and T-BIL >15 mg/dl (P < 0.001), and not with CS use (P = 0.10). Accumulative incidence of infection was not different between patients with and without CS (P = 0.18)., Conclusions: Corticosteroid use did not significantly increase the incidence of infection. Two weeks after introduction of CS is a critical point for evaluating treatment response, avoiding infectious complications and switching to LT., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT., Methods: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed., Results: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01)., Conclusions: Two-week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Aim: The prognosis of patients with acute liver failure has improved dramatically in the past three decades due to advances in medical critical care and use of liver transplantation (LT) in Western countries, where the etiology of acute liver failure is different from that in Japan. We analyzed patients with fulminant hepatitis (FH) and late‐onset hepatic failure (LOHF) admitted to our unit over a 32‐year period to clarify the nature of Japanese patients with FH and LOHF. Methods: A total of 137 Japanese patients with FH and LOHF between 1986 and 2017 were analyzed for etiologies, disease types, treatment protocols, and outcome. Results: Of 137 patients, 124 were FH (53 acute type and 71 subacute type) and 13 LOHF. The major etiology was due to viral infections in 48% of patients. A total of 23.4% of patients recovered without LT, 7.3% received LT, and 69.3% died without LT. The number of patients showed rise and fall without an evident decrease during the period. Patients with autoimmune hepatitis increased after the establishment of autoimmune hepatitis criteria in 1999 (p < 0.001), and that with indeterminate cause decreased (p < 0.01). The mean age was older in the last decade than in the first decade (p = 0.036). Spontaneous and overall survival rates were not different during the period. Conclusions: The prognosis of our patients with FH and LOHF has not improved, probably because of aging and the increasing proportion of etiologies with poor prognosis and difficult‐to‐treat patients without response to medications regardless of advancement of clinical management, including artificial liver support devices and LT. [ABSTRACT FROM AUTHOR]

Background: In Western countries, most patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). The number of patients with UC in East Asia has increased markedly over the past two decades. However, current clinical features of PSC and of PSC associated with UC (PSC-UC) have not yet been clarified in East Asia, particularly in Japan. We aimed to reveal the clinical courses and associations with UC in Japanese patients with PSC from the mutual viewpoint of PSC and UC. Methods: We retrospectively retrieved medical records of patients with PSC (69) and UC (1242) who were diagnosed at Chiba University Hospital between June 1991 and August 2017. Results: In the present cohort, 37 patients had PSC-UC; the cumulative risks of PSC in patients with UC and of UC in patients with PSC were 3.0% and 53.6%, respectively. We confirmed similar distinctive results by a Japanese nationwide survey, noting that younger patients with PSC had a notably high possibility of association with UC. From the viewpoint of the UC cohort, the occurrence of right-sided disease was significantly higher in patients with PSC-UC than in those with UC (16.2% vs. 4.2%, P = 0.003). Pancolitis was more commonly observed in PSC-UC, and proctits/left-sided colitis was less commonly found in patients with UC. The number of patients with young-onset PSC-UC may be increasing similar to an increase in patients with UC in Japan. Conclusions: In our cohort, the comorbidity rate of PSC-UC was higher than that obtained in previous reports. The incidence of PSC-UC and UC may increase in the future in East Asia, particularly in Japan. [ABSTRACT FROM AUTHOR]

Aim There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF. Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro-inflammatory cytokine levels in the early stage of ALF. Methods Ten consecutive adult Japanese patients with fulminant hepatitis in the early stage, three treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group) and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical data on admission were matched between the groups and retrospectively analyzed for serum concentrations of interleukin-6, tumor necrosis factor-α, and interleukin-1β over a 2-week period. Results Mean cytokine levels on admission were not different between the two groups. Tumor necrosis factor-α was significantly reduced on day 7 in patients with CS. Serum levels of pro-inflammatory cytokines tended to be reduced in patients with CS compared to those without during the observation period, although the differences were not significant. Conclusions It might be possible that introduction of CS pulse therapy in the early stage of ALF could reduce levels of pro-inflammatory cytokines, which might inhibit the cascade of progression of ALF. [ABSTRACT FROM AUTHOR]

Background: Corticosteroid (CS) has been introduced in most acute liver failure (ALF) patients for the purpose of suppressing pro‐inflammatory cytokines in Japan where a shortage of donor livers exists, whereas CS use is evaluated to be no benefit in Western countries. In the present study, we aimed to clarify the association between infectious complications and CS use in ALF, and determine when to evaluate treatment response and consider the timing for switching to liver transplantation (LT). Methods: Corticosteroid was administered to patients in the early stage prospectively. Clinical and biochemical features of 110 adult patients were analyzed. Results: Corticosteroids were administered to 78 (71%) patients. The duration between start of CS and onset of infection was 17 ± 10 days. Multivariate analysis revealed that infection was associated with age >50 years (P = 0.034) and T‐BIL >15 mg/dl (P < 0.001), and not with CS use (P = 0.10). Accumulative incidence of infection was not different between patients with and without CS (P = 0.18). Conclusions: Corticosteroid use did not significantly increase the incidence of infection. Two weeks after introduction of CS is a critical point for evaluating treatment response, avoiding infectious complications and switching to LT. Highlight Aiming to clarify the association between infectious complications and corticosteroid use in acute liver failure, Yasui and colleagues showed that corticosteroid use did not significantly increase the incidence of infection and that two weeks after corticosteroid initiation was a critical point for evaluating treatment response and switching to liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis (AIH) is one of major etiologies of acute liver failure (ALF), and the survival rate without liver transplantation (LT) of patients with fulminant AIH is especially poor worldwide. We investigated the clinicopathological features of infectious complications in autoimmune ALF retrospectively and tried to determine when to continue corticosteroid (CS) treatment or abandon it for LT. Methods: Twenty patients with autoimmune ALF, comprising five severe hepatitis, 13 fulminant hepatitis and two late onset hepatic failure, were analyzed. Results: Corticosteroids were administered to 19 patients. Seventeen infectious complications were observed in 12 patients. The median (range) duration between the introduction of CS and onset of infection was 15 (10–41) days. There were no significant differences in clinicobiochemical features between patients with and without infection. Of 20 patients, eight (40%) recovered without LT, four (20%) received LT and eight (40%) died without LT. Dead or transplanted patients had more advanced liver failure on admission than recovered ones (P < 0.01). Conclusions: Two‐week after the introduction of CS is a critical point for avoiding infectious complications. Therefore, we should have evaluated efficacy of CS and performed LT by then at the latest in case of failure to improve. Highlight Fujiwara and colleagues reveal that the critical point for switching to liver transplantation without infectious complications in autoimmune acute liver failure is two weeks after the start of corticosteroid treatment. It is crucial to evaluate corticosteroid efficacy and, if no improvement is seen, to perform liver transplantation by that time. [ABSTRACT FROM AUTHOR]

Aim Acute liver failure ( ALF) is a worldwide problem despite its rare incidence because of its extremely high mortality. There are no beneficial therapies except for emergency liver transplantation for ALF. However, in Japan where the problem of a shortage of donor livers still remains, therapies other than transplantation must be further investigated for patients with ALF. Our aim was to elucidate the efficacy of high-dose corticosteroid ( CS) in decreasing liver enzyme levels in the early stage of ALF. Methods Thirty-one consecutive Japanese patients with viral ALF in the early stage were prospectively examined for their clinical and biochemical features and treatment responses during 2 weeks after the start of treatment. Nineteen were treated with high-dose methylprednisolone, and 12 having clinical and biochemical backgrounds with no significant difference were treated without CS. Results The aspartate aminotransferase : alanine aminotransferase ratio became lower in patients treated with CS than in controls ( P < 0.05). Fifteen of 19 patients in the CS group and eight of 12 in the control group recovered ( P = 0.36). Hepatitis B viral infection and advanced liver damage at the start of treatment were associated with poor prognosis ( P < 0.05). Complications during the therapy were not greater in the CS group than control ( P = 0.64). Conclusion The introduction of high-dose CS in the early stage of ALF was effective in suppressing the destruction of hepatocytes. CS-treated patients showed slightly higher survival rates and slightly more improved liver regeneration than controls, although the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis of acute liver failure due to autoimmune hepatitis is often difficult because of atypical clinicopathological features. Patients with autoimmune acute liver failure are sometimes resistant to immunosuppressive therapy and have poor prognosis. Although their survival rates are especially poor (5-20%) without liver transplantation in Japan, their clinicopathological features have remained uncertain. A major problem is that there is no gold standard for making the diagnosis of acute onset autoimmune hepatitis. If there are diagnosing tools supporting clinicopathological features, they are of benefit to the patients. We examined computed tomography (CT) imaging features of autoimmune acute liver failure to clarify the usefulness of imaging for the diagnosis. Methods: A retrospective analysis of 129 unenhanced CT scans of 68 patients with acute hepatitis, consisting of 23 with autoimmune acute liver failure (ALF) (group 1), 25 with early admission-viral ALF (group 2) and 20 with late admission-viral ALF (group 3), was performed. Results: Autoimmune acute liver failure showed heterogeneous hypoattenuating areas and viral ALF diffuse ones ( P < 0.001). The diffuse hypoattenuating areas were present in none of group 1, 15 (60%) of group 2, and 7 (30%) of group 3. The heterogeneous hypoattenuating areas were present in 15 (65%) of group 1, none of group 2 and 1 (5%) of group 3. Conclusions: Heterogeneous hypoattenuation on unenhanced CT was a characteristic CT imaging feature of autoimmune acute liver failure compared with viral ALF. This finding could be one of the tools for diagnosing autoimmune acute liver failure in combination with clinicopathological features. [ABSTRACT FROM AUTHOR]

Background and aims: Diagnosis of the acute presentation of autoimmune hepatitis (AIH) is difficult because patients do not always show typical clinicopathological features of AIH. Although some of them progress to fulminant hepatitis, the survival rate of which is <20% without liver transplantation, their clinicopathological features have remained uncertain. We examined them for a better understanding and improvement of the prognosis of 'life-threatening' severe and fulminant AIH. Methods: Clinical, biochemical and pathological features of 28 patients with severe or fulminant AIH and treatment responses were examined retrospectively. Results: At the time of admission, mean immunoglobulin G was 2479 ± 1170 mg/dl, with 7 (25%) patients showing normal levels. Anti-nuclear antibody was ≤1:40 in 8 (29%). Liver histology showed severe activity in 95% and acute hepatitis in 86% of the patients. Centrilobular necrosis including submassive and massive necrosis was characteristic. Of the 25 patients treated with corticosteroids, 17 responded and 8 did not. Responders to corticosteroids showed younger age and higher prothrombin time (PT) activity than non-responders at the time of corticosteroid administration. The improvement of PT activity during 2 weeks and 4 weeks and total bilirubin level during 4 weeks was statistically significant in responders, but not in non-responders. Conclusions: We should diagnose and treat acute onset AIH patients before they develop into severe and fulminant disease. Performing liver biopsy at the early stage of acute onset AIH, evaluating the biopsy specimens precisely and initiating corticosteroid therapy may be essential for improving the prognosis without liver transplantation. [ABSTRACT FROM AUTHOR]

After the establishment of the international criteria of autoimmune hepatitis (AIH) in 1999 and the recognition of acute onset AIH, the diagnosis of patients with fulminant type of AIH came to be made. We diagnosed autoimmune fulminant liver failure based on the criteria, and discussed the etiology of fulminant hepatitis (FH) and late onset hepatic failure (LOHF), and the characteristics of autoimmune fulminant liver failure. We investigated the etiology of 95 consecutive adult patients with FH or LOHF admitted to our liver unit between 1990 and 2009. Clinical and biochemical features, therapies and outcomes were examined in patients with AIH after 2000. Of 95 patients, 85 were FH and 10 LOHF. The etiology was due to viral infections in 51.6% (hepatitis A virus in 7.4%, hepatitis B virus in 43.2% and hepatitis E virus in 1.1%), AIH in 15.8%, drug allergy-induced in 12.6%, and unknown causes in 20.0%. The rate of patients with AIH increased significantly between 2000 and 2009 compared to the rate between 1990 and 1999 ( P = 0.002). In recovered patients with AIH without transplantation after 2000, coma grade was lower, alanine aminotransferase level, prothrombin time activity and alfa-fetoprotein level were higher than in the others with statistical significance. AIH is not a rare cause of FH and LOHF, and the number of patients with unknown causes would surely decrease in concert with the precise diagnosis of AIH. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Brennan et al papers. To view these articles visit https://doi.org/10.1111/apt.14566 and https://doi.org/10.1111/apt.14975. [ABSTRACT FROM AUTHOR]