Scientific letter
Severe intrahepatic cholestasis as the initial manifestation of light chain amyloidosis
Colestasis intrahepática grave como manifestación inicial de la amiloidosis por depósito de cadenas ligeras
Diego Martínez-Acitores de la Mataa,
, Silvia Bravo Meléndeza, Candela Ceballos Bolañosb, Irene Amat Villegasc, María Carmen Mateos Rodriguezb, Mara Pilar Huarte Muniesaa, Susana Oquiñena Legaza, Montserrat Alvarellos Outeriob, Sara Pérez Ricarted
Corresponding author
a Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona, Spain
b Department of Haematology, Complejo Hospitalario de Navarra, Pamplona, Spain
c Department of Pathology, Complejo Hospitalario de Navarra, Pamplona, Spain
d Department of Internal Medicine, Complejo Hospitalario de Navarra, Pamplona, Spain
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Pathology, Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Internal Medicine, Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Colestasis intrahepática grave como manifestación inicial de la amiloidosis por depósito de cadenas ligeras" ] ] "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" => 1737 "Ancho" => 1674 "Tamanyo" => 397469 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Liver cell trabeculae are compressed by marked amyloid deposition in the sinusoids. Abundant acellular pink material (black arrows) on a H&E stain is seen in this high magnification picture. (B) The presence of amyloid was confirmed by apple green birefringence on Congo Red staining with polarized microscopy. The deposit was observed both in the sinusoids (arrows) as well as in the vessels wall (black star). (C, D) FDG-PET showed signs of hepatic infiltration (SUVmax<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.3) and axial skeleton bone marrow heterogeneous hypercaptation (SUVmax L2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.2).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Amyloidosis is a rare disease characterized by deposition of insoluble, fibril-forming amyloid proteins in the extracellular space of organs, eventually producing insufficiency and end-organ dysfunction. The most common form of amyloidosis is light-chain (AL) amyloidosis. AL amyloidosis is a clonal plasma cell disorder, being the kidney, heart and peripheral nerves the most commonly organs affected.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1–4</span></a> Liver is often involved histologically (60–92%) in patients with AL amyloidosis, but most cases are clinically asymptomatic.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This research presents the case of a 70-year-old man, without relevant past medical history, admitted to our hospital with progressive jaundice, choluria and abdominal distension for 2 weeks. There was no history of weight loss, encephalopathy or gastrointestinal bleeding. On physical examination, the patient presented generalized jaundice, mild peripheral edema and hepatomegaly, with a palpable liver until 3<span class="elsevierStyleHsp" style=""></span>cm below the right costal margin. Laboratory data showed hyperbilirubinemia (7.5<span class="elsevierStyleHsp" style=""></span>mg/dl) and cholestasis enzymes elevation (alkaline phosphatase 1273<span class="elsevierStyleHsp" style=""></span>U/L; gamma-glutamyl transferase 705<span class="elsevierStyleHsp" style=""></span>U/L). Hemogram, coagulation and renal function were both normal. Ultrasonography and computed tomography (CT) of the abdomen revealed hepatomegaly and portal hypertension signs, such as paraumbilical vein recanalization and mild quantity of ascites. Serologies for hepatitis A, B, C and E viruses, CMV, EBV and HIV were negative. Anti-nuclear, anti-mitochondrial and anti-smooth muscle antibodies were negative. Serum immunoglobulins (IgG, IgA, IgM) were negative. Proteinogram (alpha-1 globulin, alpha-2 globulin, beta globulin), ceruloplasmin and alpha 1-antitrypsin were in normal range.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Due to the existence of an acute cholestatic hepatitis with non-identified etiological agent, we performed a percutaneous liver biopsy. The liver tissue biopsy showed perisinusoidal deposition of an eosinophilic amorphous substance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Examination under polarized light of sections stained with Congo red demonstrated apple-green birefringence (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Immunohistochemistry staining was negative for amyloid A and λ light chain, and positive for κ light chain. The histopathological diagnosis was an AL amyloidosis with κ light chain deposits.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The hematological study showed evidence of a monoclonal plasma cell proliferative disorder, appreciating in the laboratory data the presence of a serum and urine M protein, abnormal serum free light chain and serum protein electrophoresis (SPEP) IgG kappa. Clonal plasma cells could also be identified in the bone marrow. We observed 2.4% plasma cells with aberrant immunophenotype, so multiple myeloma presence was ruled out.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Bence Jones protein was detected in urine, yet kidney involvement was not found. Transthoracic echocardiogram (TTE) and electrocardiogram do not show cardiac involvement. Neurophysiological study was carried out, without appreciating signs of polyneuropathy or myopathy. Positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) was then performed to complete the study, revealing the presence of signs of hepatic infiltration and axial skeleton bone marrow heterogeneous hypercaptation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C, D).</p><p id="par0030" class="elsevierStylePara elsevierViewall">While making the assessment, liver function worsened. The patient experienced a deterioration of the liver biochemistry, with bilirubin 24.1<span class="elsevierStyleHsp" style=""></span>mg/dl and ALP 1065<span class="elsevierStyleHsp" style=""></span>U/L, and developed moderate ascites, with good response to diuretic treatment. Signs of acute liver failure were not seen during assessment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore, with the diagnosis of AL amyloidosis with exclusively liver involvement, chemotherapy treatment was initiated with bortezomib (adjusted-dose 0.7<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>, according to data sheet because of hyperbilirubinemia), cyclophosphamide and dexamethasone. Clinical and laboratory improvement was initially achieved, bringing bilirubin levels down to 10<span class="elsevierStyleHsp" style=""></span>mg/dl four weeks after initiation of treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">However, one month later the patient was readmitted to hospital due to hepatic decompensation with ascites, spontaneous bacterial peritonitis and bilateral pneumonia and finally died due to respiratory failure.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The clinical spectrum of hepatic amyloidosis can range from hepatomegaly (most frequently physical sign observed) and mild abnormal liver function tests, to more severe symptoms rarely observed, such as jaundice, intrahepatic cholestasis, portal hypertension, hepatic failure or spontaneous liver rupture.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3–5</span></a> Jaundice and intrahepatic cholestasis as the primary manifestation of the disease is very uncommon (<5% cases).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Hyperbilirubinemia and marked elevation of serum alkaline phosphatase may indicate a poor prognosis of hepatic amyloidosis.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3–5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Diagnosis of hepatic amyloidosis is based on a high clinical suspicion, exclusion of other infiltrative disorders of the liver (tuberculosis, sarcoidosis, malignancy and glycogen storage diseases) and tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2,4,5</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Treatment of AL amyloidosis is based on chemotherapy to eradicate the underlying clone, usually combinations of bortezomib, cyclophosphamide and dexamethasone.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2,4</span></a> Patient who meet the criteria will be eligible for autologous hematopoietic cell transplantation.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Liver involvement in patients with amyloidosis is often an indicator of poor prognosis,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> having been reported as 9 months the median survival of patients with primary hepatic amyloidosis.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3–5</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">There are no financial or other conflicts of interest regarding this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1737 "Ancho" => 1674 "Tamanyo" => 397469 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Liver cell trabeculae are compressed by marked amyloid deposition in the sinusoids. Abundant acellular pink material (black arrows) on a H&E stain is seen in this high magnification picture. (B) The presence of amyloid was confirmed by apple green birefringence on Congo Red staining with polarized microscopy. The deposit was observed both in the sinusoids (arrows) as well as in the vessels wall (black star). (C, D) FDG-PET showed signs of hepatic infiltration (SUVmax<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.3) and axial skeleton bone marrow heterogeneous hypercaptation (SUVmax L2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.2).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hepatic amyloidosis in 98 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.A. Park" 1 => "P.S. Mueller" 2 => "R.A. Kyle" 3 => "D.R. Larson" 4 => "M.F. Plevak" 5 => "M.A. Gertz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Medicine (Baltimore)." 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Carvalho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000496185" "Revista" => array:6 [ "tituloSerie" => "GE Port J Gastroenterol" "fecha" => "2019" "volumen" => "26" "paginaInicial" => "425" "paginaFinal" => "429" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31832498" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amyloidosis of the gastrointestinal tract and the liver: clinical context, diagnosis and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "U. Syed" 1 => "R.A. Ching Companioni" 2 => "H. Alkhawam" 3 => "A. Walfish" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Eur. J. Gastroenterol. Hepatol." "fecha" => "2016" "volumen" => "28" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02105705/0000004400000001/v1_202101130647/S0210570520302429/v1_202101130647/en/main.assets" "Apartado" => array:4 [ "identificador" => "9030" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105705/0000004400000001/v1_202101130647/S0210570520302429/v1_202101130647/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570520302429?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 0 | 4 |
| 2024 October | 37 | 6 | 43 |
| 2024 September | 43 | 6 | 49 |
| 2024 August | 37 | 9 | 46 |
| 2024 July | 47 | 4 | 51 |
| 2024 June | 36 | 2 | 38 |
| 2024 May | 28 | 4 | 32 |
| 2024 April | 31 | 5 | 36 |
| 2024 March | 58 | 5 | 63 |
| 2024 February | 50 | 2 | 52 |
| 2024 January | 39 | 1 | 40 |
| 2023 December | 36 | 2 | 38 |
| 2023 November | 27 | 6 | 33 |
| 2023 October | 37 | 2 | 39 |
| 2023 September | 21 | 0 | 21 |
| 2023 August | 11 | 2 | 13 |
| 2023 July | 33 | 1 | 34 |
| 2023 June | 28 | 3 | 31 |
| 2023 May | 32 | 4 | 36 |
| 2023 April | 33 | 1 | 34 |
| 2023 March | 16 | 5 | 21 |
| 2023 February | 15 | 6 | 21 |
| 2023 January | 12 | 11 | 23 |
| 2022 November | 3 | 3 | 6 |
| 2022 October | 5 | 5 | 10 |
| 2022 September | 5 | 4 | 9 |
| 2022 August | 5 | 7 | 12 |
| 2022 July | 2 | 1 | 3 |
| 2022 June | 1 | 2 | 3 |
| 2022 March | 1 | 0 | 1 |
| 2021 November | 4 | 0 | 4 |
| 2021 September | 1 | 0 | 1 |
| 2021 July | 1 | 0 | 1 |
| 2021 June | 2 | 0 | 2 |
| 2021 May | 1 | 0 | 1 |
| 2021 April | 1 | 0 | 1 |
| 2021 March | 1 | 2 | 3 |
| 2021 February | 4 | 2 | 6 |
| 2021 January | 3 | 3 | 6 |
Show all
