Features Of Autoimmune Hepatitis Research Articles

Primary Biliary Cholangitis Overlap With Autoimmune Hepatitis? A Case Report

Primary biliary cholangitis (PBC) is a chronic, autoimmune cholestatic disease, characterized by inflammation of the small and medium-sized bile ducts, which can lead to cirrhosis. Two to nineteen percent of patients with PBC have been reported to have features that overlap with autoimmune hepatitis (AIH). We report a case of a 39-year-old man with changes in liver biochemistry, with 6 years of asymptomatic evolution, whose diagnostic investigation determined the diagnosis of PBC, however with some features of AIH. J Med Cases. 2021;12(4):131-133 doi: https://doi.org/10.14740/jmc3623

Worse Response to Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients with Autoimmune Hepatitis Features

Background: There is limited evidence on the treatment response of primary biliary cholangitis (PBC) with autoimmune hepatitis (AIH) features but not meet the criteria of PBC-AIH syndromes. The aim of this study was to elucidate the clinical characteristics of PBC patients with features of AIH. Methods: We included patients with diagnostic criteria of PBC. All patients were treated with ursodeoxycholic acid (UDCA) and without immunosuppressive agents for >1 year. The biochemical response was evaluated at 1 year after the treatment of UDCA. Results: Among 432 patients with PBC, 166 (38.4%) patients did not achieve biochemical response within 1 year of UDCA treatment. Nonresponders had a lower albumin level and higher immunoglobulin G, alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase, glutamyl transpeptidase and total bilirubin levels (p < 0.05). The response rates were significantly lower in patients with elevated level of IgG or ALT or AST. Moreover, the higher the IgG or AST level was, the lower the response rate was in patients with PBC, regardless of cirrhosis. For patients with cirrhosis, there was no differences among patients with different levels of ALT. Patients in the PBC with AIH features group had a significant lower response rate than patients in the PBC-only group. Among the 139 patients who underwent liver biopsy, 54 were nonresponsive to UDCA and 48 (88.9%) shown mild interface hepatitis. Conclusion: In conclusion, PBC patients with AIH features had a worse response to UDCA therapy.

Autoimmune liver diseases

Autoimmune liver diseases comprise aspectrum of progredient idiopathic inflammatory diseases. Typical histological features of autoimmune hepatitis (AIH) include the pattern of chronic hepatitis with predominant plasma cell-rich interface activity, rosetting of hepatocytes, and emperipolesis. Florid bile duct lesions are the key feature of primary biliary cholangitis (PBC); onion-like periductal fibrosis characterizes the primary sclerosing cholangitis (PSC). Variants of AIH, or overlap syndromes, show intersecting histomorphologic findings with PBC or PSC. The diagnosis of the different autoimmune inflammatory liver diseases is based on clinical presentation, a hepatitic or cholestatic pattern of liver enzymes, immuno-serological findings, image analysis in PSC, and liver biopsy as afacultative or obligatory adjunct. Liver biopsy plays amajor role in the diagnosis of AIH, small-duct PSC, AMA-negative PBC, IgG4-related diseases, overlap syndrome, and in the recognition of concurrent liver diseases, especially drug-induced liver diseases. Herewith pathologists can help clinicians find adequate therapy for different autoimmune inflammatory liver diseases.

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

Особенности течения аутоиммунного гепатита у женщин перименопаузального периода: ретроспективное исследование

Особенности течения аутоиммунного гепатита у женщин перименопаузального периода: ретроспективное исследование

Features and outcome of AIH patients without elevation of IgG.

Background & AimsHigh IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored.MethodsIn a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up.ResultsOut of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels.ConclusionsCompared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.Lay summaryA characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.

IgG4 associated autoimmune hepatitis: A rare entity

Background: IgG4-related disease is an immune mediated multisystem disorder fibroinflammatory condition. Two types of hepatic involvement in IgG4 related disease have been described: IgG4 hepatopathy and IgG4 related autoimmune disease,1 which is rare with only few cases reported. Case report: We present a case of 50-year-old lady who presented with a history of malaise and nausea, and had deranged LFTs, raised IgG4 and serum lipase levels, and positive ANA and SMA antibodies. Abdominal CT showed no bile duct abnormality. Liver biopsy showed features of autoimmune hepatitis with grade III activity. Unusually, a significant amount of pericapsular tissue was present which showed fibroinflammatory reaction with infiltration of IgG4 bearing plasma cells. No significant bile duct damage was seen. The patient fulfilled the diagnostic criteria for definite AIH using IAIHG scoring system and responded well with steroid therapy. Conclusion: The diagnostic criteria for IgG4 associated autoimmune hepatitis are not well defined and additional studies are needed to clarify the clinical significance and diagnostic guidelines.2

Primary Sclerosing Cholangitis With Features of Autoimmune Hepatitis: Exploring the Global Variation in Management.

Patients with primary sclerosing cholangitis (PSC) frequently manifest features of autoimmune hepatitis (AIH). We sought to understand factors affecting expert management, with the goal of facilitating uniformity of care. A Survey Monkey questionnaire with four hypothetical cases suggesting a potential AIH/PSC variant was sent to hepatologists spanning global practices. Eighty responses from clinicians in 23 countries were obtained. Most of the respondents would request a liver biopsy, and stated that the cases presented could not be appropriately managed without a biopsy. Despite the fact that histology did not unequivocally support an AIH/PSC variant in three of the four cases, this diagnosis was reached by most of the respondents for all cases, except case 1, in which 49% were diagnosed with AIH/PSC. There was a wide variation of suggested medical treatment. For three cases, the most commonly chosen treatment options did not exceed 35%, indicating a lack management consensus. Most respondents would treat with ursodeoxycholic acid, despite current American Association for the Study of Liver Diseases guidelines, either alone or in combination with immunosuppression. European clinicians recommended ursodeoxycholic acid more frequently than their counterparts in North America (P < 0.05 in three out of four cases), who advocated the use of immunosuppression alone more commonly than Europeans (P = 0.005 in case 2). Conclusions: We document a wide variation in clinical decision making in the context of managing patients with a potential AIH/PSC variant. Guidance, likely based on systematic studies arising from prospective registries, is needed to better address this difficult clinician problem.

IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis

Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

1354 It's Not Always PSC: An Intriguing Case of IgG-4 Sclerosing Cholangitis

INTRODUCTION: IgG4-related disease has a broad spectrum of clinical manifestations, when it involves the biliary tract it is termed as IgG4-associated cholangitis. It is the most frequent extra-pancreatic manifestation of type 1 autoimmune pancreatitis and shares clinical and radiographic features with Primary Sclerosing Cholangitis however differentiation is important. CASE DESCRIPTION/METHODS: 71-year-old female with a known history of recurrent pancreatitis and cholangitis status post laproscopic cholecystectomy presented to the hospital with abdominal pain and obstructive pattern of LFTs. Previous ERCPs had revealed common bile duct stricture and a stent had been placed. Prior CT, ultrasound and MRCP all were consistent with findings of pancreatitis with pancreatic duct dilation along with dilation of the intra-hepatic ducts. Endosonographic imaging of the pancreas demonstrated a markedly abnormal pancreas However CA19-9 was normal. She underwent repeat ERCP with biliary dilatation revealing multiple biliary strictures and underwent stent placement in the common bile duct and right hepatic duct. Cytology did not reveal malignant cells and core liver biopsy showed preserved hepatic architecture with no evidence of fibrosis. Features of autoimmune hepatitis are not identified. She presented in a couple of months with similar abdominal pain and ERCP revealed a new 2 cm hepatic duct stricture which was stented. Due to recurrent strictures in the biliary system with failed response to recurrent endoscopic stenting a multi disciplinary decision was made to repeat liver biopsy which revealed very dense lymphoplasmacytic inflammatory infiltrates, numerous lymphoid follicles and obliterative phelebitis similar to findings noted in type I autoimmune pancreatitis. IgG-4 liver stains performed highlighted multiple positive plasma cells establishing the diagnosis of IgG4-sclerosing cholangitis. She was started on steroids and noted to have improvement in her liver enzymes. DISCUSSION: The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult however necessary as the former is steroid responsive where as the latter are not. Serum IgG-4 levels are highly predictive for IgG-RD. Tissue acquisition is absolutely essential for the diagnosis. We present a challenging case where due to non-conclusive histological evidence the diagnosis was delayed and later a portal-based inflammatory nodule was seen which is a characteristic feature of this disease.

3195 Autoimmune Hepatitis With Primary Biliary Cirrhosis: An Overlapping Syndrome of the Liver

INTRODUCTION: Autoimmune liver diseases consist of Primary Biliary Cirrhosis (PBC), Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC). Overlap syndromes are defined when there are characteristic features of AIH along with PBC and PSC. We report the presentation and management of an AIH-PBC overlap syndrome. CASE DESCRIPTION/METHODS: A 60-year-old Asian female with a past history of hypertension, presented with fatigue, myalgia, nausea, vomiting, and icterus for ten days. She denied the use of illicit drugs, alcohol consumption or family history of liver disease. On arrival, she had a temperature of 38.2°C, a pulse of 110 beats/minute, blood pressure of 100/70 mm Hg, and oxygen saturation of 97% on room air. Physical exam revealed icterus 1+, and mild tenderness in the right hypochondriac area. Laboratory investigations revealed leukocyte count of 15.2 K/ul, alanine transaminase of 1107 U/l, aspartate aminotransferase of 1010 U/l, alkaline phosphatase of 685 U/l, total bilirubin of 10 mg/dl with the direct component of 9 mg/dl, and gamma-glutamyl transferase of 666 U/l. Further workup revealed anti-nuclear antibody titer of 1:1000, antimitochondrial antibody (AMA) titer of 1:80 with negative peripheral antineutrophil cytoplasmic antibody and hepatitis serology. Ultrasound of the abdomen showed common-bile duct (CBD) stricture formation. The patient underwent endoscopic retrograde cholangiopancreatography with sphincterotomy and stenting. Liver biopsy showed interface hepatitis with portal tract inflammation. Brush border sampling from the CBD revealed lymphocytic and neutrophilic infiltrate. A diagnosis of AIH-PBC overlap syndrome was made. She was started on piperacillin/tazobactam 4.5 gm and metronidazole 400 mg along with with ursodeoxycholic acid (UDCA) 300 mg, thrice a day. After a month, the stent was removed and there was a resolution of symptoms with normalization of liver enzymes. DISCUSSION: The minimum criteria required for the diagnosis of AIH-PBC overlap syndrome include positive AMA and histology showing bile duct abnormality in an otherwise classical AIH (Table 1). Management is usually with UDCA, immunosuppressants, and corticosteroids. It is prudent to maintain a modest index of suspicion of overlap syndromes in patients such as ours. Early diagnosis and appropriate management are of paramount importance.

2267 Drug-Induced Autoimmune Hepatitis From Valerian Root Tea

INTRODUCTION: Differentiating drug induced liver injury from other causes of acute hepatitis, especially autoimmune hepatitis can be difficult secondary to overlapping histological features and confounding laboratory abnormalities. Stopping the offending drug should usually result in resolution of liver injury. We describe a rare case of drug induced liver injury secondary to valerian root tea with overlapping features of autoimmune hepatitis which resolved with limited duration steroid therapy. CASE DESCRIPTION/METHODS: Our patient is a 47-year-old female with hypothyroidism who presented with acute onset of generalized abdominal discomfort, jaundice and vomiting without fever or confusion. She denied prior similar episodes. She reported regular use of valerian tea for insomnia for a duration of 3 months prior to presentation. Physical examination revealed jaundice, mild diffuse abdominal tenderness and no features of chronic liver disease. Labs showed elevated alanine aminotransferase of 2741 U/L, aspartate aminotransferase of 1847 U/L, alkaline phosphatase of 199 U/L, total bilirubin of 9.2 mg/dL, albumin of 3.4 g/dL and International normalized ratio of 1.4. Autoimmune work up revealed positive smooth muscle antibody, mildly elevated Immunoglobulin G of 1980 mg/dL and negative antinuclear and mitochondrial antibodies. Viral hepatitis panel was negative. Imaging of the abdomen was unremarkable. Liver biopsy showed severe acute hepatitis with extensive necroinflammatory activity with plasma cells and bridging necrosis without significant fibrosis. With no significant improvement in liver enzymes after stopping valerian root tea and with concern for autoimmune hepatitis, she was started on prednisone 60 mg daily with improvement of transaminitis. Transaminases have remained normal for several months after stopping prednisone (Table 1, Figure 1). DISCUSSION: Diagnosing autoimmune like drug induced liver injury and differentiating it from autoimmune hepatitis can be difficult. Steroids should be considered in cases with severe or prolonged elevation of liver enzymes that do not resolve after stopping the offending drug. Valerian root can cause severe form of autoimmune like drug induced liver injury that responds to steroids. Complete recovery is possible with steroids for limited duration. Relapse following steroid cessation should prompt further evaluation for autoimmune hepatitis.

Histologic patterns of liver injury induced by anti-PD-1 therapy.

BackgroundNivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1 (PD-1)—have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them.MethodsEight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients.ResultsSeven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy.ConclusionsOur study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients.

Síndrome de superposición hepatitis autoinmune - colangitis biliar primaria

Introducción: Los síndromes de superposición son aquellas enfermedades hepáticas que simultáneamente presentan características de hepatitis autoinmune (HAI), colangitis biliar primaria (CBP) o colangitis esclerosante primaria (CEP).&#x0D; Objetivo: Describir un caso clínico de síndrome de superposición HAI-CBP.&#x0D; Material y métodos: Se realizó un estudio descriptivo, retrospectivo, presentación de caso clínico sobre síndrome de superposición HAI-CBP.&#x0D; Resultados: Presentamos el caso clínico de un paciente masculino de 48 años, con diagnóstico de síndrome de superposición HAI-CBP, quien cumple dos de los tres criterios de París: alanina aminotransferasa (ALT) &gt; 5 del límite superior normal y hepatitis de interfase para HAI; anticuerpos antimitocondriales (AMA) positivos y fosfatasa alcalina (FAL) &gt; 2 límite superior normal para CBP, la respuesta al tratamiento combinado con esteroides más ácido ursodesoxicólico (UDCA) fue excelente.&#x0D; Conclusiones: Por la baja prevalencia de esta entidad no existen ensayos aleatorizados sobre el tratamiento ideal, dosis y vía de administración

Effects of adenovirus‐induced hepatocyte damage on chronic bile duct inflammation in a sclerosing cholangitis mouse model

Four major autoimmune diseases target the liver. They develop because of bile duct destruction, leading to chronic cholestasis or result from hepatocyte damage like autoimmune hepatitis (AIH). Interestingly, some patients simultaneously show features of both cholangitis and AIH. Our goal was to mimic such concurrent characteristics in a mouse model that would help deciphering mechanisms possibly involved in an inflammatory crosstalk between cholestatic disease and hepatitis. Mdr2-/- mice, which spontaneously develop sclerosing cholangitis because of accumulation of toxic bile salts, were infected with adenovirus (Ad) encoding human Cytochrome P4502D6 (hCYP2D6), the major target autoantigen in type-2 AIH, to trigger hepatocyte injury. Wild type FVB mice were controls. Resulting Ad-Mdr2-/- mice presented with cholangitis, fibrosis and cellular infiltrations that were higher than in Mdr2-/- or Ad-FVB mice. Increased levels of anti-neutrophil cytoplasmic antibodies but similar anti-hCYP2D6 antibody titres were detected in Ad-Mdr2-/- compared to Mdr2-/- and Ad-FVB mice respectively. IFNγ-expressing hCYP2D6-specific CD4 T cells declined, whereas hCYP2D6-specific CD8 T cells increased in Ad-Mdr2-/- compared to Ad-FVB mice. The overall T cell balance in Ad-Mdr2-/- mice was a combination of a type 17T cell response typically found in Mdr2-/- mice with a type 1 dominated T cell response characteristic for Ad-FVB mice. Simultaneously, the type 2T cell compartment was markedly reduced. Experimental hepatitis induction in a mouse with sclerosing cholangitis results in a disorder which represents not simply the sum of the individual characteristics but depicts a more complex entity which urges on further analysis.

Validation, clinical utility and limitations of the Amsterdam-Oxford model for primary sclerosing cholangitis

Recently the Amsterdam-Oxford model (AOM) was introduced as a prognostic model to assess the risk of death and/or liver transplantation (LT) in primary sclerosing cholangitis (PSC). We aimed to validate and assess the utility of the AOM. Clinical and laboratory data were collected from the time of PSC diagnosis until the last visit or time of LT or death. The AOM was calculated at yearly intervals following PSC diagnosis. Discriminatory performance was assessed by calculation of the C-statistic and prediction accuracy by comparing the predicted survival with the observed survival in Kaplan-Meier estimates. A grid search was performed to identify the most discriminatory AOM threshold. A total of 534 patients with PSC and a mean (SD) age of 39.2 (13.1) years were included. The diagnosis was large duct PSC in 466 (87%), PSC with features of autoimmune hepatitis in 52 (10%) and small-duct PSC in 16 (3%). During the median (IQR) follow-up of 7.8 (4.0-12.6) years, 167 patients underwent LT and 65 died. The median LT-free survival was 13.2 (11.8-14.7) years. The C-statistic of the AOM ranged from 0.67 at baseline to 0.75 at 5 years of follow-up. The difference between the predicted and observed survival ranged from -1.6% at 1 year to + 3.9% at 5 years of follow-up. Patients that developed AOM scores >2.0 were at significant risk of LT or death (time-dependent hazard ratio 4.09; 95% CI 2.99-5.61). In this large cohort of patients with PSC, the AOM showed an adequate discriminative performance and good prediction accuracy at PSC diagnosis and during follow-up. This study further validates the AOM as a valuable risk stratification tool in PSC and extends its utility. In our study we assessed whether the Amsterdam-Oxford model (AOM) is able to correctly estimate the risk of liver transplantation or death in patients with primary sclerosing cholangitis (PSC). This model uses 7 objective and readily available variables to estimate prognosis for individual patients at the time of PSC diagnosis. The AOM may aid in patient counselling and timing of diagnostic procedures or therapeutic interventions for complications of liver disease. We confirm that the model works well at PSC diagnosis, but also when the AOM is recalculated at different timepoints during follow-up, greatly improving the applicability of the model in clinical practice and for individual patients.

Direct-Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis.

Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV‐positive (HCV+) study group that had elevated serum markers of AIH before starting direct‐acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre‐DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow‐up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.

Treatment response in primary biliary cholangitis: The role of autoimmune hepatitis features

Introduction and aimPrimary biliary cholangitis is a rare disease with scarce epidemiological data in Southern Europe. The authors aimed to evaluate treatment response in a cohort of patients. Materials and methodsThis retrospective observational single-centre study included patients with diagnostic criteria of primary biliary cholangitis. Data on disease presentation, laboratory results, treatment and clinical endpoints were collected and analyzed. ResultsFifty-three patients were included, 89% women, with mean age of 62±15 years at diagnosis. The majority was asymptomatic (49%), tested positive for antimitochondrial antibodies (96%) and had increased alkaline phosphatase (median=214U/L). 75% of the patients had liver histology and the majority were in Ludwig's stage I (42%). Autoimmune hepatitis (AIH) features were found in seven patients (13%). All were treated with ursodeoxycholic acid (UDCA) and 56% achieved biochemical response at one year; patients with AIH features exhibited steeper decreases in alkaline phosphatase (p=0.007) and reached the endpoint of 40% decrease in alkaline phosphatase more frequently (p=0.017). ConclusionIn conclusion a significant proportion of patients failed to achieve an adequate response to UDCA treatment. The response rate of patients with AIH features was better, which could be related to a different phenotype or to the potential impact of immunosuppressive agents.

SUN-578 Severe Hyperbilirubinemia Due to Graves' Thyrotoxicosis

Introduction: Graves’ disease is the most common cause of hyperthyroidism in the United States. Though hepatic dysfunction has been described in patients with thyrotoxicosis due to Graves’ disease, it is an extremely rare cause of severe hyperbilirubinemia. There is limited evidence to guide physicians in the management of hyperthyroidism associated with liver dysfunction, making it a diagnostic and therapeutic challenge. Case Report: 30-year-old woman with no significant history presented with complaints of diarrhea and yellowish discoloration of skin for more than a month. She had generalized itching, hand tremors and a 30 lb. weight loss during this period. On physical examination, she was noted to have tachycardia, scleral icterus, a diffuse non-nodular non-tender goiter, bilateral fine tremors and hyperreflexia. Abdomen was soft and non-tender with no hepatosplenomegaly. Laboratory evaluation showed normal compete blood count, total bilirubin 26 mg/dL, direct bilirubin 17.7 mg/dL, indirect bilirubin 9.1 mg/dL, ALT 49 IU/L, AST 26 IU/L, ALP 265 IU/L. She had biochemical hyperthyroidism with TSH less than 0.01 UIU/ml (0.45-4.5), free T4 of 4 ng/dL (0.6-1.3), total T3 371 ng/dL (79-149). TSI was elevated 2.13 (0-0.55). Further work up of hyperbilirubinemia including hepatitis viral panel, anti-nuclear antibody, anti-mitochondrial and anti-smooth muscle antibodies were negative. Ultrasound of the liver showed no abnormalities. Liver biopsy revealed benign liver with bland canalicular stenosis in central zones. There were no features of autoimmune hepatitis or chronic hepatitis. She underwent I131 ablation with normalization of ALP and bilirubin levels at 3 months follow-up. Discussion: Hepatic dysfunction has been described in patients with hyperthyroidism since it was reported in 1874. It may occur because of hyperthyroidism per se, drug treatment of hyperthyroidism and conditions associated with autoimmune thyroid disease like autoimmune hepatitis and primary biliary cirrhosis. The causes could also be unrelated to hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, medications. Several theories have been hypothesized, but the mechanism of the hepatic dysfunction due to hyperthyroidism per se is not clear. A thorough work up is essential to rule out other potential etiologies. If clinically feasible, liver biopsy may be deferred initially. However, it should be considered if liver function fails to improve despite normalization of thyroid hormone levels. I131 ablation is a safe and effective method of treatment in these patients.

A case of melatonin-induced biochemical flare in a patient with primary sclerosing cholangitis with features of autoimmune hepatitis.

A case of melatonin-induced biochemical flare in a patient with primary sclerosing cholangitis with features of autoimmune hepatitis.