Scientific letter
Autoimmune severe acute fulminant hepatic failure (FHF) during pregnancy
Insuficiencia hepática aguda grave (IHAG) fulminante de origen autoinmune en gestante
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Caballero-Mateos, María Ángeles López Garrido, Patricia Becerra Massare, Javier de Teresa Galván" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Antonio M." "apellidos" => "Caballero-Mateos" "email" => array:1 [ 0 => "ogy1492@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María Ángeles" "apellidos" => "López Garrido" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Patricia" "apellidos" => "Becerra Massare" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Javier" "apellidos" => "de Teresa Galván" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Aparato Digestivo y Hepatología, Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Insuficiencia hepática aguda grave (IHAG) fulminante de origen autoinmune en gestante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1396 "Ancho" => 1649 "Tamanyo" => 118444 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Progress during hospital stay. PI, prothrombin index (%); TB, total bilirubin (mg%); Bx, liver biopsy; ALT (IU/ml); Tx, liver transplantation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute liver failure (ALF) is an uncommon syndrome due to severe deterioration of liver cell function that may require an emergency liver transplantation (ETx). Clinical signs include a decrease in prothrombin index (PI) (<40%) and hepatic encephalopathy. Severe ALF can be fulminant when it appears within <2 weeks of clinical onset or subfulminant if it appears within 2–8 weeks.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In Spain, approximately one third of ALF cases are due to hepatitis B virus (HBV) infection, although around 5% are due to autoimmune hepatitis (AIH). This figure, however, is underestimated since cases caused by non-classical phenotype AIH are classified as cryptogenic ALF.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our case study is a 29-year-old female patient, with no significant medical history, who was 20 weeks pregnant. She was referred to the hospital after suffering from jaundice and choluria for 2 days. She had no risk factors for hepatic diseases and said she had not travelled recently or consumed any drugs/hepatotoxic substances. She had yellow discolouration of the skin and sclera (jaundice) but was alert and oriented and had no asterixis. At admission, her lab test results were: AST 3205<span class="elsevierStyleHsp" style=""></span>IU/ml, ALT 2664<span class="elsevierStyleHsp" style=""></span>IU/ml, direct bilirubin 12.9<span class="elsevierStyleHsp" style=""></span>mg%, indirect bilirubin 3.1<span class="elsevierStyleHsp" style=""></span>mg%, leukocytes 13,820/mm<span class="elsevierStyleSup">3</span>, INR 1.91 and PI 43% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The Doppler ultrasound was normal. The Obstetrics department confirmed it was a normal pregnancy. Hepatotropic virus results (HAV, HBV, HCV, HDV, HEV, CMV, EBV and herpes simplex) were negative, while autoantibody screen results (ANA-1/320, SMA-1/320 and AMA-1/320 and IgG–IgA–IgM–IgE 1870–235–79–124<span class="elsevierStyleHsp" style=""></span>mg/dl) were positive. Other serological test results (copper, ceruloplasmin and α-1 antitrypsin) were normal. No percutaneous/transjugular liver biopsy (biopsy) was performed due to abnormal clotting and foetal radiation. In accordance with consensus criteria,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–5</span></a> a diagnosis of autoimmune hepatitis with overlap syndrome (ANA+, AMA+) was considered.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> On day 5, a course of methylprednisolone was started (50<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h-<span class="elsevierStyleSmallCaps">IV</span>/10 days followed by a tapering dose regimen). On day 6, the patient deteriorated: malleolar and pretibial oedema, grade II encephalopathy (<span class="elsevierStyleItalic">flapping</span> +), blood pressure 24.2<span class="elsevierStyleHsp" style=""></span>mg%, INR 1.8, PI 40%, factor <span class="elsevierStyleSmallCaps">V</span> 72% and urine sediment normal. Her condition was classified as fulminant ALF with MELD score of 24<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). On day 8, encephalopathy was grade III and the possibility of an ETx was contemplated since 3 of the <span class="elsevierStyleItalic">King's College</span> criteria (non-A, non-B hepatitis; TB<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mg%; and duration of jaundice before onset of encephalopathy >7 days) were met. After 24<span class="elsevierStyleHsp" style=""></span>h, the patient improved (PI 54%, INR 1.5, TB 18.6<span class="elsevierStyleHsp" style=""></span>mg%, AST/ALT 307/665<span class="elsevierStyleHsp" style=""></span>IU/ml), ruling out an ETx. On day 26, once PI had returned to normal, a percutaneous biopsy was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): grade 2, stage 2 AIH, “portal inflammation with necrosis of the limiting plate and bridging periportal fibrosis, with destruction of bile ducts and disappearance of interlobular bile ducts” (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). On day 43, the patient was discharged with normal obstetric control, almost normal lab test results and tapered doses of corticosteroids<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>azathioprine (50<span class="elsevierStyleHsp" style=""></span>mg/day). Three days later, she suffered a miscarriage. After 4 months, all lab test results were normal and autoantibody screen results were negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">AIH presents in episodes, attacking both healthy livers and livers affected by prior flare-ups.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–5</span></a> Diagnosis can be difficult when features of the classical phenotype are absent<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4</span></a>; therefore, the <span class="elsevierStyleItalic">International AIH Group</span> defined several score-based diagnostic criteria,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–5</span></a> with liver biopsy results (not pathognomonic) being essential for diagnosis.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> As in our case, AIH sometimes overlaps with primary biliary cholangitis criteria. This overlap syndrome is more a clinical than a histological entity, sharing features of both AIH (predominant phenotype) and cholestasis (Paris and EASL criteria),<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> and must be interpreted within the context of a systemic autoimmune phenomenon. Only follow-up will determine the direction in which each process will develop.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4–6</span></a> Almost 6% of AIH cases start out as ALF, requiring differential diagnosis with viral hepatitis, Wilson's disease and α-1 antitrypsin deficiency, in addition to other concomitant or pre-existing hepatic processes associated exclusively with pregnancy (second trimester) (preeclampsia, HELLP, intrahepatic cholestasis and acute fatty liver of pregnancy). The diagnosis of such processes tends to be simple using clinical, analytical and ultrasound data.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7–9</span></a> A probable diagnosis of AIH is sufficient to be able to start steroid therapy early, with prognosis and the need for ETx depending on early treatment. Our patient was placed on the ETx list but did not actually receive a transplant since her symptoms improved within 48<span class="elsevierStyleHsp" style=""></span>h. The difficulty of personalising the need for ETx using parameters/criteria of varying strictness<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,10</span></a> due to the presence of false negatives and positives (as in our case) has resulted in these criteria being reviewed in multi-centre studies between various ETx units.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> There is a state of immune tolerance during pregnancy due to hyperoestrogenaemia (induces shift from Th<span class="elsevierStyleInf">1</span> response to Th<span class="elsevierStyleInf">2</span> response or changes in anti-inflammatory cytokine profile).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> This may explain spontaneous improvement in some cases of AIH during pregnancy and the appearance of acute episodes towards the end of pregnancy or postpartum once oestrogen levels fall. Prior to modern-day treatments, rates of foetal morbidity and mortality and complications in pregnant women were high.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Today, pregnancy in a woman with AIH is safe for both the mother and her foetus, provided that she receives proper pre-natal care.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> In our case, the patient suffered a miscarriage 3 days after discharge, and it seems reasonable to say that AIH<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ALF were responsible for this given that steroid treatment is considered safe during pregnancy. To summarise, a fast differential diagnosis is necessary in the event of acute liver symptoms in pregnant women, when resulting in ALF, along with early immunosuppressant therapy, with prognostic value, even before reaching a definite histological diagnosis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Caballero-Mateos AM, López Garrido MÁ, Becerra Massare P, de Teresa Galván J. Insuficiencia hepática aguda grave (IHAG) fulminante de origen autoinmune en gestante. Gastroenterol Hepatol. 2018;41:259–260.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1396 "Ancho" => 1649 "Tamanyo" => 118444 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Progress during hospital stay. PI, prothrombin index (%); TB, total bilirubin (mg%); Bx, liver biopsy; ALT (IU/ml); Tx, liver transplantation.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 689 "Ancho" => 975 "Tamanyo" => 182827 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Liver biopsy: rosette formation. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 21 | 3 | 24 |
| 2024 September | 34 | 7 | 41 |
| 2024 August | 32 | 4 | 36 |
| 2024 July | 28 | 5 | 33 |
| 2024 June | 30 | 2 | 32 |
| 2024 May | 30 | 3 | 33 |
| 2024 April | 31 | 4 | 35 |
| 2024 March | 44 | 6 | 50 |
| 2024 February | 41 | 1 | 42 |
| 2024 January | 36 | 2 | 38 |
| 2023 December | 37 | 3 | 40 |
| 2023 November | 48 | 5 | 53 |
| 2023 October | 49 | 2 | 51 |
| 2023 September | 37 | 7 | 44 |
| 2023 August | 38 | 7 | 45 |
| 2023 July | 21 | 1 | 22 |
| 2023 June | 36 | 4 | 40 |
| 2023 May | 56 | 11 | 67 |
| 2023 April | 32 | 0 | 32 |
| 2023 March | 31 | 2 | 33 |
| 2023 February | 15 | 3 | 18 |
| 2023 January | 34 | 7 | 41 |
| 2022 December | 40 | 7 | 47 |
| 2022 November | 33 | 3 | 36 |
| 2022 October | 38 | 10 | 48 |
| 2022 September | 52 | 12 | 64 |
| 2022 August | 43 | 8 | 51 |
| 2022 July | 26 | 9 | 35 |
| 2022 June | 15 | 12 | 27 |
| 2022 May | 31 | 6 | 37 |
| 2022 April | 34 | 5 | 39 |
| 2022 March | 26 | 7 | 33 |
| 2022 February | 29 | 3 | 32 |
| 2022 January | 29 | 7 | 36 |
| 2021 December | 25 | 8 | 33 |
| 2021 November | 36 | 10 | 46 |
| 2021 October | 20 | 10 | 30 |
| 2021 September | 22 | 14 | 36 |
| 2021 August | 13 | 9 | 22 |
| 2021 July | 13 | 7 | 20 |
| 2021 June | 20 | 9 | 29 |
| 2021 May | 32 | 12 | 44 |
| 2021 April | 31 | 3 | 34 |
| 2021 March | 15 | 15 | 30 |
| 2021 February | 14 | 11 | 25 |
| 2021 January | 8 | 10 | 18 |
| 2020 December | 21 | 7 | 28 |
| 2020 November | 10 | 3 | 13 |
| 2020 October | 8 | 2 | 10 |
| 2020 September | 16 | 7 | 23 |
| 2020 August | 15 | 12 | 27 |
| 2020 July | 23 | 10 | 33 |
| 2020 June | 16 | 10 | 26 |
| 2020 May | 13 | 12 | 25 |
| 2020 April | 54 | 4 | 58 |
| 2018 July | 0 | 0 | 0 |
| 2018 June | 1 | 0 | 1 |
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