Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Anand L ，Choudhury A ，Bihari C ，Sharma BC ，Kumar M ，Maiwall R ，Siam Tan S ，Shah SR ，Hamid S ，Butt AS ，Jafri W ，Chawla YK ，Taneja S ，Duseja A ，Dhiman RK ，Mahtab MA ，Ghazinyan H ，Duan Z ，Chen Y ，Shukla A ，Hu J ，Abbas Z ，Treeprasertsuk S ，Lesmana LA ，Lesmana CR ，Sollano JD ，Carpio G ，Sahu MK ，Kumar G ，Sarin SK ，APASL ACLF (APASL ACLF Research Consortium) Working Party ... -  《-》

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Sharma S ，Agarwal S ，Saraya A ，Choudhury AK ，Saigal S ，Soin AS ，Shukla A ，Sahu MK ，Lesmana LA ，Lesmana RC ，Shah SN ，Hu J ，Tan SS ，Jothimani D ，Rela M ，Ghazinyan HL ，Amrapurkar DN ，Eapen CE ，Goel A ，Payawal DA ，Hamid S ，Butt AS ，Zhongping D ，Singh V ，Duseja A ，Sood A ，Midha V ，Al Mahtab M ，Kim DJ ，Ning Q ，Kulkarni AV ，Rao PN ，Lee GH ，Treeprasertsuk S ，Shaojie X ，Karim MF ，Sollano JD ，Kalista KF ，Gani RA ，Prasad VGM ，Sarin SK ，APASL ACLF Research Consortium (AARC) for APASL ACLF working party ... -  《-》

Determinants of Outcomes in Autoimmune Hepatitis Presenting as Acute on Chronic Liver Failure Without Extrahepatic Organ Dysfunction upon Treatment With Steroids.

Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids. In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified. Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-day transplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%). Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.

Sharma S ，Agarwal S ，Gopi S ，Anand A ，Mohta S ，Gunjan D ，Yadav R ，Saraya A ... -  《-》

Acute presentation of autoimmune hepatitis -from acute hepatitis to ALF and ACLF.

Acute presentation of autoimmune hepatitis (AIH) occurs in 22-43% of all AIH cases, and is not a rare condition. Rather than constituting a single disease entity, it represents a clinical spectrum characterized by considerable variability in severity and the presence of preexisting chronic AIH. This spectrum ranges from acute AIH and acute severe AIH to AIH presenting as acute liver failure (ALF) or as acute-on-chronic liver failure (ACLF), contingent upon factors such as coagulopathy, hepatic encephalopathy, and underlying liver disease. Diagnosing acute presentation of AIH can be particularly challenging due to the frequent absence of classical serologic signatures such as autoantibodies and elevated IgG levels. Histopathological examination remains essential for diagnosis, typically necessitating percutaneous or transjugular liver biopsy. Corticosteroids (CS) are recommended for the management of acute AIH and acute severe AIH with coagulopathy. However, the therapeutic response to CS should be meticulously monitored. If a poor response is anticipated, liver transplantation (LT) should be promptly considered. For AIH presenting as ALF with encephalopathy or ACLF with advanced underlying liver disease, LT is generally advised. Nonetheless, there is potential for a trial of CS therapy in cases of ALF with low MELD scores or ACLF without encephalopathy. This review provides an overview of the latest findings concerning the definition, diagnosis, and management of acute presentation of AIH.

Tanaka A ，Harada K 《-》

Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure.

Gupta T ，Dhiman RK ，Rathi S ，Agrawal S ，Duseja A ，Taneja S ，Chawla Y ... -  《-》