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Mini-laparoscopy of a patient with acute liver failure due to newly diagnosed autoimmune hepatitis exemplarily showing the right liver lobe with diffuse capsular swelling, regenerative nodules, and rounded lower margin (upper panel) (A), and liver histology of the same patient with AIH-induced ALF (B). Left panel demonstrating severe inflammation with interface hepatitis (original magnification 200 ×) and the right panel with higher magnification (400 ×) revealing numerous plasma cells extending from the portal tract into the adjacent parenchyma (lower panel).
Source publication
AIM
To investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH).
METHODS
A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defin...
Contexts in source publication
Context 1
... was diagnosed according to the "Diagnostic Scoring System of the International Autoimmune Hepatitis Group" including analysis of auto-antibodies, IgG-levels, histological features, and exclusion of viral markers [18,19] . Liver histology was available for the whole study population and was obtained either by percutaneous- or laparoscopy-guided biopsy ( Figure 1A and B). Only adult patients (age ≥ 18 years) were included in the study. ...
Context 2
... out of 565 patients with AIH suffered from ALF as their initial presentation (9.2%) ( Figure 1A and B) and were included in the study. Mean age of the study population was 43.6 ± 14.9 (19-76) years while the majority was of female gender (44/52, 84.6% ipilimumab (n = 1), and rivaroxaban (n = 1)] followed by previous acute viral infections [8/26 (30.8%), namely Epstein-Barr virus (n = 4), Cytomegalovirus (n = 3), and hepatitis E virus (n = 1)]. ...
Context 3
... this retrospective study between 01/2005 and 04/2017, a total of 565 patients with histologically- proven AIH were analyzed, from whom 52 previously healthy patients suffered from ALF as their initial presentation of autoimmune hepatitis. According to the criteria defined by the "American Association for the Study of the Liver (AASLD)", ALF was diagnosed by elevation of liver enzymes in combination with hepatic encephalopathy (HE) and coagulopathy (INR > 1.5) in the absence of a pre-existing chronic liver disease [14] . AIH was diagnosed according to the "Diagnostic Scoring System of the International Autoimmune Hepatitis Group" including analysis of auto-antibodies, IgG-levels, histological features, and exclusion of viral markers [18,19] . Liver histology was available for the whole study population and was obtained either by percutaneous- or laparoscopy-guided biopsy ( Figure 1A and B). Only adult patients (age ≥ 18 years) were included in the study. The University Clinic of Essen ethics committee approved the retrospective, anonymous analysis of the data and the study was conducted according to the principles expressed in the Declaration of Helsinki. All patients gave their written informed consent prior to study ...
Context 4
... out of 565 patients with AIH suffered from ALF as their initial presentation (9.2%) ( Figure 1A and B) and were included in the study. Mean age of the study population was 43.6 ± 14.9 (19-76) years while the majority was of female gender (44/52, 84.6% ipilimumab (n = 1), and rivaroxaban (n = 1)] followed by previous acute viral infections [8/26 (30.8%), namely Epstein-Barr virus (n = 4), Cytomegalovirus (n = 3), and hepatitis E virus (n = 1)]. Finally, the remaining 3 patients underwent previous surgery in general anesthesia (11.5%) (Figure ...
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Citations
... To date, the etiology of AIH is still unknown, and other causes of acute or chronic liver disease must be excluded in order to diagnose AIH. It is hypothesized that AIH develops in individuals with a certain genetic background due to environmental factors (triggering factors such as drugs or biological agents), suggesting that they have awakened latent autoimmunity [7][8][9]. This assumption is underlined by strong genetic associations within genes of the human leukocyte antigen (HLA) region (the human major histocompatibility complex, MHC), which are involved in the presentation of antigenic peptides to T cells and are therefore implicated in the initiation of an adaptive immune response [10]. ...
Background and aims: Autoimmune hepatitis (AIH) is a complex and progressive inflammatory liver disease characterized by immune-mediated destruction of the liver parenchyma, hypergammaglobulinemia, the presence of circulating autoantibodies, and good response to immunosuppressive therapy. Since the prevalence of AIH is relatively rare, data on the clinical course and the long-term outcome are scarce. Patients and methods: We retrospectively analyzed the data of 535 well-documented AIH patients treated at the University Hospital Essen between 2000 and 2020. Results: The majority of patients were middle-aged females (75% women, mean age 45 years) with AIH type 1 (97%). Approximately 32% of patients were diagnosed with cirrhosis due to AIH, 29% had concomitant autoimmune (predominantly autoimmune thyroiditis), and 10% had psychiatric diseases, respectively. Skin tumors were the most common malignant diseases (47% of all tumors), while hepatocellular carcinoma rarely occurred (only six cases). Overall long-term mortality and liver-associated mortality were 9.16% and 4.67%, respectively. However, long-term survival was strongly associated with disease remission. Conclusions: Although AIH is a silent disease and cirrhosis is present in many cases, a favorable long-term prognosis can be achieved by consequent immunosuppressive therapy. The incidence of (liver-associated) complications seems to be lower in comparison to other etiologies, such as viral hepatitis or NASH, and mainly depends on the long-term side effects of immunosuppressive therapy.
... Based on evolving diagnostic standards, autoimmune hepatitis is now recognized as an etiology for ALF, accounting for a substantial percentage of the heretofore indeterminate cases [16]. One group reported a specific inciting event in approximately half of patients with autoimmune ALF, usually drugs such as NSAIDS and antibiotics in addition to acute viral infections [17]. Clinical criteria include serum globulin concentration, absence of hepatitis viral markers and presence of various autoantibodies. ...
... hepatitis patients may have a genetic predisposition and are quiescent and undiagnosed until the drug triggers an autoimmune response [17]. The literature is not clear regarding any characteristic imaging findings in patients with autoimmune hepatitis [18]. ...
Acute liver failure (ALF) is a rare clinical entity with high morbidity and mortality frequently requiring liver transplantation for survival. Imaging, particularly with ultrasound, plays an important role, especially to distinguish patients with underlying chronic liver disease who have lower transplant priority. We discuss the clinical and imaging findings in the three subtypes of ALF using a multi-modality approach with an emphasis on ultrasound.
... In suspected autoimmune hepatitis biopsy would help in further management and may assist in the identification of a cause that may have precipitated liver failure. 242 It will also be useful in drug Induced hepatitis 243 and ALF due to obscure reasons where there is a possibility of etiology influencing management significantly and where ACLF is a strong differential diagnosis or cannot be excluded otherwise, 244 and very rare instances in ALF due to metabolic disorders. 245 ...
Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature has regional differences, which affects the clinical presentation and natural course. In this part of the consensus paper designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication has been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to anti-tuberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, sub-acute liver failure as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short term mortality. Death is usually attributable to cerebral complications, infections, and resultant multi-organ failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until liver transplantation can be arranged. It is equally important to assess prognosis to select patients that are suitable for LT. Several prognostic scores have been proposed and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part-2 of this document.
... In addition, major histocompatibility complex HLA-loci (HLA-DR3 and HLA-DR4) are reported to have a strong association with AIH [3]. Interestingly, a recent study demonstrated that drugs, viral infections, and surgery in general anesthesia might trigger ALF as the initial presentation of AIH [4]. Thus, the genetic risk factor in combination with environmental factors, which are involved in the disruption of immune tolerance to the autologous liver antigens, leads to the onset of AIH. ...
... The aetiology of AIH is unclear, but it may be triggered by viruses. Buechter Matthias et al. [21] demonstrated that drugs, viral infections, and previous surgery may trigger acute liver failure (ALF) as the initial presentation of AIH. Navarta Luz et al. [22] reported that a relationship between hepatitis C virus (HCV) infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases, and a link among the presence of a variety of autoantibodies simultaneously with SMA, increased Gamma-glutamyl transferase (GGT) levels and HCV titres in a population of male patients. ...
The seroprevalenc of autoimmune hepatitis (AIH)-related antibodies in patients, particularly Asians, with acute hepatitis E (AHE) is unclear. In this study, we investigated whether acute hepatitis E virus (HEV) infection is associated with the seroprevalence of AIH-related autoantibodies and assessed their impact on the disease characteristics. AIH-related autoantibodies were detected by indirect immunofluorescence in 198 AHE patients and 50 type 1 AIH patients. The positivity rates of against nuclear antigen (ANA) and smooth muscles antibody (SMA) in AHE patients were 37.4% and 22.7%, and the total positivity rate was 50%. Compared to those in AIH patients, the positivity rates of ANA-H and SMA-AA were significantly lower (35.1% vs. 82.1% and 4.4% vs. 88.4%). Female gender and the ALT level, but not immunosuppressive or antiviral drugs, were independently predictive of the presence of AIH-related autoantibodies in AHE patients. Fifty-two patients positive for AIH-related autoantibodies were followed up for 12 months. During this period, 33 of them became negative and 19 remained positive, albeit with significantly decreased titres. In conclusions, the seroprevalence of AIH-related autoantibodies in AHE patients was elevated, particularly in females, but their subspecificities and titres differed from those of type 1 AIH. Acute HEV infection may be related to AIH.
Abbreviations: AIH: autoimmune hepatitis; AHE: acute hepatitis E; ANA: against nuclear antigen; SMA: smooth muscles antibody; ANA-H: ANA with homogeneous pattern; SMA-AA: SMA with anti-actin pattern; Anti-LKM1: anti- liver-kidney microsomes-1 antibody; ANCA: anti-neutrophil cytoplasmic antibody; AMA: anti-mitochondrial antibody; Anti-SLA: anti-soluble liver antigen; Anti-LC1: anti-liver cytoplasmic type 1 antibody; pANCA: perinuclear antineutrophil cytoplasmic antibody
... The AHRQ score of each study was presented in Table 1 and Supplemental Digital Content (Appendix 3, http:// links.lww.com/MD/D462) ( Table), which illustrates the detailed AHRQ score. Ten studies [23][24][25][26][27][28][29][30][31][32] were of high quality and 15 studies [6,7,[33][34][35][36][37][38][39][40][41][42][43][44][45] were of moderate quality. There were no studies with low quality. ...
... Both this study and Anand et al study [48] have shown that glucocorticoid was beneficial in patients with liver failure or fulminant hepatitis. In recent Buechter et al study, [23] all patients were treated with 1 mg/kg/d of glucocorticoid. The 28-day mortality or liver transplantation rate was 17.3%. ...
Background:
Glucocorticoid as the standard treatment of autoimmune hepatitis has been recommended with different doses. The purpose of this study is to compare the efficacy and safety of high and low doses for clinical practice.
Methods:
Medline, Embase, and Cochrane Library were searched until January 16th, 2019 for cohort studies or randomized controlled trials in patients with autoimmune hepatitis. Glucocorticoid 60 mg/d or 1 mg/kg/d was defined as high dose and 40 to 50 mg/d or 0.5 mg/d as low dose. Outcome of interests includes the incidence of the biochemical remission, adverse event, and endpoint events. Double arcsine method with a random-effect model was used to combine the incidence. Potential heterogeneity was explored by meta-regression and subgroup analysis.
Results:
Overall, 25 studies (3305 patients) were included, with 10 studies in the high dose group and 15 in low dose group. The biochemical remission rate in the high and low dose group was 0.79 (95% confidence interval [CI] [0.72, 0.85]) and 0.72 (95% CI [0.65, 0.78]), respectively. The incidence of endpoint events and adverse event in the high were slightly higher (0.03, 95% CI [0.02, 0.04]; 0.42, 95% CI [0.30, 0.53]) than that of the low dose group (0.01, 95% CI [0.00, 0.01]; 0.39, 95% CI [0.15, 0.63]).
Conclusions:
For autoimmune hepatitis patients, 60 mg/d or 1 mg/kg/d of glucocorticoid gives higher biochemical remission rate and higher incidence of endpoint events and adverse events.
... 3,30 AIH may also manifest as ACLF, with clinical characteristics equal to ALF. 28 It is thought that about 20% to 30% of the patients develop an acute course and to an even lesser extent ALF, which might be induced by a triggering agent including toxic injury, preceding viral infections, or therapy with immune-modifying drugs. 32 For the substantiation of diagnosis, apart from the related clinical appearance, positive serum autoantibodies, remission under glucocorticoids as well liver biopsy are required; liver biopsy in an AIH-mediated ALF setting seems to be safe and effective in diagnosing AIH, and corticosteroid therapy is not associated with sepsis or high mortality and might improve the outcome. 33 Autoantibodies that can be found in high titers in serum include, for instance, antinuclear antibody, antiactin antibody, anti-soluble liver antigen, and quantitative immunoglobulins. ...
... 34 Advanced age and high model of end-stage liver disease (MELD) score are related with lethal outcome. 32 Drug-induced ALF is uncommon, varies geographically, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. 4,35 Its main representative constitutes acetaminophen hepatotoxicity. ...
Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available. © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
... Подчеркнем, все больше внимания привлекают к себе случаи дебюта АИГ, связан- ные с воздействием именно триггерных факто- ров. Соответственно, иммуноопосредованные реакции могут быть инициированы токсически- ми, в частности, лекарственными воздействиями, вызванными реактивными метаболитами лекар- ственных препаратов, вирусными вакцинами [8], инфекцией, в том числе вирусами гепатита А, В, С, герпеса человека 6-го типа (HHV-6) и просто- го герпеса типа 1 (HSV-1), вирусом Эпштейна - Барр [9]. С расширением спектра лекарственных средств на фармацевтическом рынке выявляются «новые» триггеры АИГ. ...
Autoimmune hepatitis is a progressive immune-mediated liver disease of unknown etiology. Its key characteristics include hyper-gammaglobulinemia, circulating autoantibodies, and periportal inflammation seen in a liver biopsy sample. It is not infrequent that the lack of unified diagnostic tests makes the verification of the disease very challenging. Most patients respond well to standard immunosuppressive therapy; however, a significant proportion of them demonstrate side effects and disease relapses after treatment withdrawal. A wide range of side effects of systemic steroids and eventual disruptions with azathioprine (the agent of choice in the treatment algorithms for autoimmune hepatitis) supplies to the Russian market make it relevant to use alternative treatment regimens. In the real world practice, alternative treatment regimens are rarely used in such patients due to the absence of hard evidence of their efficacy. Low prevalence of autoimmune hepatitis, multiplicity of its clinical types, as well as a lack of understanding of its pathogeneticmechanisms hinder the synthesis of new agents and performing trials with already known immunosuppressants with a statistical power necessary to obtain persuasive data. One of solutions of the problem could be the accumulation of clinical data into registries for further systematization of the knowledge and formulation of new clinical guidelines.
Acute liver failure (ALF) has a mortality rate of more than 40%. Currently, orthotopic liver transplantation is the sole clinical treatment for ALF, but its wide usage is severely limited due to donor shortage and immunological rejection. An emerging and promising technology for ALF treatment is liver tissue engineering (LTE), wherein porous scaffolds serve as a crucial component. Nanofiber scaffolds, which mimic the inherent structures of fibrous extracellular matrix well, provide an ideal environment for cell growth and tissue regeneration. Recently, several functional nanofiber scaffolds for LTE have been developed, which show impressive results in regulating cell function and repairing liver injury when combined with appropriate seeding cells and/or growth factors. This review firstly introduces the etiologies and treatment indicators of ALF. Subsequently, typical fabrication technologies of nanofiber scaffolds and their related applications for function regulation of liver-related cells and treatment of ALF are comprehensively summarized. Particular emphasis is placed on the strategies involving an appropriate combination of suitable seeding cells and growth factors. Finally, the current challenges and the future research and development prospects of nanofiber scaffold-based LTE are discussed. This review will serve as a valuable reference for designing and modifying novel nanofiber scaffolds, further promoting their potential application in LTE and other biomedical fields.
