Management of Difficult Cases of Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a complex autoimmune disease characterized by immune-mediated destruction of hepatic parenchyma which can result in cirrhosis, liver failure, and death. Current American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of Liver (EASL) guidelines recommend corticosteroids alone or in combination with azathioprine as first-line treatment strategies. However, a significant proportion of patients may not be able to tolerate or achieve complete biochemical response with these options. In this article, we discuss approaches to these patients and other challenging AIH patient groups such as the asymptomatic, pregnant, elderly, and liver transplant recipients

Cannabidiol (CBD) Consumption and Perceived Impact on Extrahepatic Symptoms in Patients with Autoimmune Hepatitis

Background and Aims Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile. Methods An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey. Results In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations. Conclusion CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms

Black Adult Patients With Acute Liver Failure Are Sicker and More Likely to Undergo Liver Transplantation Than White Patients

Racial and ethnic differences in the presentation and outcomes of patients wait‐listed with acute liver failure (ALF) have not been explored. Adult patients with ALF wait‐listed for liver transplantation (LT) from 2002 to 2016 were investigated using the United Network for Organ Sharing database. Clinical characteristics and causative etiologies were compared between white, black, Hispanic, and Asian patients with ALF who were wait‐listed as status 1. A competing risk analysis was used to explore differences in LT and wait‐list removal rates. Kaplan‐Meier survival curves were used to explore differences in 1‐year posttransplant survival. There were 8208 patients wait‐listed with a primary diagnosis of ALF; 4501 were wait‐listed as status 1 (55.3% of whites, 64.4% of blacks, 51.6% of Hispanics, 40.7% of Asians; P < 0.001). Black patients had higher bilirubin and Model for End‐Stage Liver Disease at wait‐listing than other groups. White patients were the most likely to have acetaminophen toxicity as a causative etiology, whereas black patients were the most likely to have autoimmune liver disease. Black patients were significantly more likely to undergo LT than white patients (hazard ratio, 1.20; 95% confidence interval, 1.08‐1.30). There was no difference in wait‐list removal because of death or clinical deterioration among racial/ethnic groups. The 1‐year posttransplant survival was lowest in black patients (79.6%) versus white (82.8%), Hispanic (83.9%), and Asian (89.3%) patients (P = 0.02). In conclusion, etiologies of ALF vary by race and ethnicity. Black patients with ALF were more likely to be wait‐listed as status 1 and undergo LT than white patients, but they were sicker at presentation. The 1‐year posttransplant survival rate was lowest among black patients

Older Age and Disease Duration Are Highly Associated with Hepatocellular Carcinoma in Patients with Autoimmune Hepatitis

Background: Hepatocellular carcinoma (HCC) is rare in patients with autoimmune hepatitis (AIH). However, the overall burden of AIH cirrhosis in causing HCC and patients' risk factors are not well understood. Aims: To characterize the proportion of HCC linked to AIH at a large academic health center, and to identify variables associated with HCC in patients with AIH in a case-control study design. Methods: Over a 14.5-year period, medical records of all patients with HCC were reviewed. Cases are AIH patients identified from the cohort, and controls are patients with AIH without HCC. Three controls were randomly chosen from the Genetic Repository of Autoimmune Liver Disease and Coexisting Exposures database for each eligible case. Results: Out of 1250 eligible patients, 20 were linked to AIH (1.6%). Their median age was 64 years, 40% men and 100% Caucasian. Ten percent of AIH patients did not have evidence of cirrhosis at HCC diagnosis. The proportion of HCCs due to AIH decreased during the time intervals of the study. Compared to controls, cases were more likely men (40.0% vs. 18%, p = 0.049), with longer AIH duration (median 16 years vs. 5 years, p = 0.004). Prolonged AIH duration (OR 1.68, p = 0.006) and older age (OR 1.15, p = 0.049) were risk factors for HCC. Conclusions: AIH is a rare cause (1.6%) for HCC in Midwestern USA with a decreasing trend over 14.5 years. Ten percent of AIH-HCC patients did not have cirrhosis at time of HCC diagnosis. Patients with prolonged duration of the disease and older age are at high risk to develop HCC

Sex disparities in waitlisting and liver transplant for acute liver failure

Background & aims: Sex disparities in liver transplantation (LT) for chronic liver disease have been described. It is unclear if similar disparities exist for acute liver failure (ALF). Methods: Adults waitlisted for LT from 2002 to 2016 with ALF were investigated using the United Network of Organ Sharing database. Clinical characteristics and causative aetiologies were compared between men and women who were waitlisted Status-1. Differences in LT, waitlist removal, and 1-year post-transplant survival were explored. Results: Of 8,408 patients waitlisted for LT with ALF, 41.3% of men and 63.9% of women were waitlisted Status-1 (p <0.001). Women had significantly higher international normalised ratio, higher frequency of grade 3-4 hepatic encephalopathy, and different aetiologies of ALF than men. On univariable analysis, women were less likely to undergo LT (subdistribution hazard ratio [SHR] 0.90; 95% CI 0.84-0.97) and were more likely to die or be removed from the waitlist as a result of clinical deterioration (SHR 1.14; 95% CI 1.002-1.30) than men. The disparities in LT (HR 0.95; 95% CI 0.87-1.03) and death/clinical deterioration (SHR 1.13; 95% CI 0.99-1.29) were no longer significant on multivariable analysis. On multivariable analysis, there was no difference in 1-year post-transplant survival between men and women. Conclusions: Women with ALF are more likely to be waitlisted Status-1 than men. There were no clear disparities in LT or waitlist removal. Sex differences in LT and waitlist removal were attenuated on fully adjusted models, suggesting that these disparities may in part be mitigated by Status-1 listing. Lay summary: Women with acute liver failure appear to be sicker than men and more often require urgent Status-1 waitlisting. There were no sex disparities in waitlist removal because of clinical deterioration or liver transplantation. This is in contrast to chronic liver disease, where sex disparities exist. The Status-1 waitlisting that women with acute liver failure receive may in part mitigate sex disparities in liver transplantation

HLA-DR Mismatch and Black Race Are Associated With Recurrent Autoimmune Hepatitis After Liver Transplantation

The predictors of recurrent autoimmune hepatitis (R-AIH) after liver transplantation (LT) are heterogeneous with limited data to guide immunosuppression, with little data on impact of race. Aims: To describe the incidence, predictors, and outcomes of R-AIH. Methods: We studied patients undergoing LT for AIH during 2000-2017 at our center. Liver biopsies were performed for clinical indications. R-AIH was defined using clinical and histologic criteria. Results: Among 75 patients undergoing LT for AIH (mean age 45 ± 16, 65% female individuals, 19% Black), 71 (95%) received antithymocyte globulin induction with tacrolimus-based immunosuppression. R-AIH developed in 20 (27%) patients at a median interval of 313 d (interquartile range, 155-1205). R-AIH was associated with level 2 HLA-DR mismatch (hazard ratio, 3.6; (95% confidence interval, 1.3-9.9; P = 0.01) and Black race (hazard ratio, 4.5; 95% confidence interval, 1.8-11.8; P = 0.002)] in the multivariable analysis. R-AIH developed in 62% of patients with level 2 HLA-DR mismatch on single-agent immunosuppression but in <20% of patients with no or 1 HLA-DR mismatch regardless of maintenance immunosuppression. R-AIH developed in 8 (57%) of 14 Black patients (71% on single-agent and 43% on dual-agent maintenance immunosuppression). Patient and graft survival were not impacted by R-AIH over a median follow-up of 8.3 y (interquartile range, 3-12). Conclusions: High-level HLA-DR mismatch and Black recipient race are associated with an increased risk of R-AIH. Immunosuppression did not predict R-AIH, but higher rates of disease recurrence with single-agent maintenance immunosuppression with these risk factors were observed and may guide maintenance immunosuppression in LT for AIH

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study

Background and Aims: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. Approach and Results: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score?matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. Conclusions: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.Fil: Efe, Cumali. Harran University Hospital; TurquíaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Lammert, Craig. University School of Medicine; Estados UnidosFil: Ebik, Berat. Gazi Yaşargil Education and Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Rıza Calışkan, Ali. Adıyaman University; TurquíaFil: Peralta, Mirta. Latin American Liver Research Educational And Awareness Network; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. University of Milano Bicocca; Italia. San Gerardo Hospital; ItaliaFil: Massoumi, Hatef. Montefiore Medical Center; Estados UnidosFil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Torgutalp, Murat. Universitätsmedizin Berlin; AlemaniaFil: Purnak, Tugrul. McGovern Medical School; Estados UnidosFil: Rigamonti, Cristina. Azienda Ospedaliera Maggiore Della Carita Di Novara; Italia. Università del Piemonte Orientale; ItaliaFil: Gomez Aldana, Andres Jose. Universidad de los Andes; ColombiaFil: Khakoo, Nidah. University of Miami; Estados UnidosFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Nazal, Leyla. Clínica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training and Research Hospita; TurquíaFil: Irak, Kader. SBU Kanuni Sultan Süleyman Training and Research Hospital; TurquíaFil: Ellik, Zeynep Melekoğlu. Ankara University Medical Faculty; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. Mardin State Hospital; TurquíaFil: Eren, Fatih. Ordu State Hospital; TurquíaFil: Cristoferi, Laura. University of Milano Bicocca; Italia. San Gerardo Hospital; ItaliaFil: Batibay, Ersin. Harran University Hospital; TurquíaFil: Urzua, Álvaro. Universidad de Chile. Facultad de Medicina.; ChileFil: Snijders, Romee. Radboud University Medical Center; Países BajosFil: Ridruejo, Ezequiel. Latin American Liver Research Educational and Awareness Network; Argentina. Cerrahpaşa School of Medicine; Turquía. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin