Fulminant hepatitis during self-medication with conjugated linoleic acid
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Drug-induced liver injury remains an important clinical concern, accounting for 4 to 10% of all adverse drug reactions.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> More than 900 drugs, toxins, and herbs have been reported to cause liver injury, and drugs account for 20-40% of all instances of fulminant hepatic failure.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Dietary supplement use has become increasingly common. An estimated 83 million Americans report using alternative medical therapies, including herbal and dietary supplements.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> People believe that natural remedies are free of adverse effects but some supplements are known to be associated with severe hepatotoxicity.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">The use of CLA as a weight loss supplement has increased in Europe and USA in last years. CLA refers to a group of positional and geometric isomers of linoleic acid that are characterized by the presence of conjugated dienes. In nature, the most abundant CLA isomer is <span class="elsevierStyleItalic">cis</span>-9, <span class="elsevierStyleItalic">trans</span>-11 (<span class="elsevierStyleItalic">c</span>9, <span class="elsevierStyleItalic">t</span>11), whereas in supplement forms CLA is typically sold as an equal mix of the two predominant isomers <span class="elsevierStyleItalic">c</span>9, <span class="elsevierStyleItalic">t</span>11 and <span class="elsevierStyleItalic">t</span>10, <span class="elsevierStyleItalic">c</span>12. Different isomers may have different effects. The effects of CLA on lipid metabolism are not yet clear and the efficacy of CLA on maintenance or achievement of a normal body weight in humans is not proven.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Possible adverse effects of CLA may be related with lipid peroxidation induction, resulting in cell damage.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">Drug-related hepatitis secondary to CLA has been previously reported in a single case worldwide.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> We report the second case of CLA induced-hepatotoxicity, this one needing hepatic transplantation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case Report</span><p id="p0025" class="elsevierStylePara elsevierViewall">A 63-year-old female patient was hospitalized with complaints of anorexia, nausea, jaundice and choluria, of 3 weeks duration.</p><p id="p0030" class="elsevierStylePara elsevierViewall">She had started CLA therapy for body fat reduction, nearly one month before, not associated with other drugs or herbal remedies. This was a purely CLA pills, containing glycerol, gelatin and water as its component parts.</p><p id="p0035" class="elsevierStylePara elsevierViewall">The patient had no exposure to other possible hepatotoxic agents during that period, and her past medical history was no remarkable.</p><p id="p0040" class="elsevierStylePara elsevierViewall">On examination she was conscious and icteric, without hepatomegaly or stigmata of chronic liver disease.</p><p id="p0045" class="elsevierStylePara elsevierViewall">At the time of admission routine liver enzyme tests revealed:</p><p id="p0050" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005"><span class="elsevierStyleLabel">•</span><p id="p0055" class="elsevierStylePara elsevierViewall">Alanine aminotransferase-2,300 U/L (normal 35 U/L).</p></li><li class="elsevierStyleListItem" id="list0010"><span class="elsevierStyleLabel">•</span><p id="p0060" class="elsevierStylePara elsevierViewall">Aspartate aminotransferase-1,100 U/L (normal 41 U/L).</p></li><li class="elsevierStyleListItem" id="list0015"><span class="elsevierStyleLabel">•</span><p id="p0065" class="elsevierStylePara elsevierViewall">Alkaline phosphatase-255 U/L (normal 104 U/L).</p></li><li class="elsevierStyleListItem" id="list0020"><span class="elsevierStyleLabel">•</span><p id="p0070" class="elsevierStylePara elsevierViewall">γ-glutamyl transferase-142 U/L (normal < 50 U/L).</p></li><li class="elsevierStyleListItem" id="list0025"><span class="elsevierStyleLabel">•</span><p id="p0075" class="elsevierStylePara elsevierViewall">Total serum bilirubin-26 mg/dL (normal < 1.2 mg/dL).</p></li><li class="elsevierStyleListItem" id="list0030"><span class="elsevierStyleLabel">•</span><p id="p0080" class="elsevierStylePara elsevierViewall">Conjugated bilirubin-21mg/dL (normal < 0.3 mg/ dL).</p></li></ul></p><p id="p0085" class="elsevierStylePara elsevierViewall">The prothrombin time was 19.3 seg (INR 1.65).</p><p id="p0090" class="elsevierStylePara elsevierViewall">The cell blood count, albumin and factor V were normal, and there was no eosinophilia.</p><p id="p0095" class="elsevierStylePara elsevierViewall">Tests for acute viral hepatitis (A, B and C), autoimmune hepatitis, hemochromatosis, α 1-antitrypsin deficiency, Wilson’s disease, and α-fetoprotein were all negative.</p><p id="p0100" class="elsevierStylePara elsevierViewall">Abdominal ultrasonography and CT scan revealed a normal liver structure, intrahepatic bile ducts, and gallbladder.</p><p id="p0105" class="elsevierStylePara elsevierViewall">Given the time course of starting CLA and the development of abnormal liver tests, the presumptive diagnosis of toxic hepatitis was made.</p><p id="p0110" class="elsevierStylePara elsevierViewall">The patient experienced an unstable clinical course during the first week of hospital admission. She developed hepatic encephalopathy and worsening of cholestasis. The prothrombin time was progressively increasing. Factor V remained in normal range. No liver biopsy was performed because clotting disturbance did not allow a percutaneous approach and transjugular biopsy was not available. The patient fulfilled the King’s College Hospital Criteria for Liver Transplantation in fulminant hepatic failure and liver transplantation was performed. Microscopic features of the disease liver showed hepatic parenchyma with extensive haemorrhagic and necrotic areas; mixed septal mononuclear cell infiltration; massive hepatic necrosis suggesting toxic liver damage (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0115" class="elsevierStylePara elsevierViewall">A full recovery occurred in this patient and she was discharged three weeks after liver transplantation maintaining periodic follow-up at Hepatology Department.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="p0120" class="elsevierStylePara elsevierViewall">We present a case of toxic hepatitis associated with CLA ingestion. To the best of our knowledge, this is the second case report of hepatotoxicity caused by this supplement. A MEDLINE search of adverse reactions to CLA retrieved one other case reported in Portugal, but with recovery after discontinuation of the CLA take.</p><p id="p0125" class="elsevierStylePara elsevierViewall">The diagnosis of acute CLA-related hepatitis was based on the patient’s history, clinical picture, abnormal results of liver function tests, exclusion of other causes of acute hepatocellular necrosis, the time association between the ingestion of the CLA and the onset of symptoms. There was no previous history of liver disease or of alcohol abuse, and the serological markers of viral and autoimmune hepatitis were negative. Abdominal ultrasound and CT scan showed no evidence of other hepatic lesions. The absence of systemic disease findings or a previous history of heart failure or hypotension excluded other causes of liver damage. Other toxic agents were ruled out, and histological findings were concordant with toxic hepatitis. Causality of toxic liver injury was assessed using the CIOMS/RUCAM scale, yielding a score of 6 (probable).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0130" class="elsevierStylePara elsevierViewall">This case highlights the importance of a thorough clinical history that considers alternative medicines, herbal remedies and unconventional diets.</p><p id="p0135" class="elsevierStylePara elsevierViewall">Physicians need to be more familiar with weight loss supplements and recognize those that are potentially harmful. It is important that such severe reactions are reported to the relevant licensing authorities. Consequently, it also raises questions regarding the regulation, licensing and safety of herbal and alternative health products.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Abbreviations</span><p id="p0140" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0010"><li class="elsevierStyleListItem" id="list0035"><span class="elsevierStyleLabel">•</span><p id="p0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CLA:</span> Conjugated linoleic acid.</p></li><li class="elsevierStyleListItem" id="list0040"><span class="elsevierStyleLabel">•</span><p id="p0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CT scan:</span> Computed tomography scan.</p></li><li class="elsevierStyleListItem" id="list0045"><span class="elsevierStyleLabel">•</span><p id="p0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CIOMS:</span> Council for international organizations of medical sciences.</p></li><li class="elsevierStyleListItem" id="list0050"><span class="elsevierStyleLabel">•</span><p id="p0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">RUCAM:</span> Roussel Uclaf Causality Assessment Method.</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Acknowledgment</span><p id="p0165" class="elsevierStylePara elsevierViewall">We would like to express gratitude to Dra. Ana Carvalho of Department of Pathologic Anatomy from Curry Cabral Hospital-Lisbon.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1207309" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1124355" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Report" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Abbreviations" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Acknowledgment" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1124355" "palabras" => array:4 [ 0 => "Conjugated linoleic acid" 1 => "Toxic hepatitis" 2 => "Fulminant hepatitis" 3 => "Liver transplantation" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">The present report describes a 63-year-old female who presented with fulminant hepatic failure requiring liver transplantation caused by a weight loss dietary supplement containing conjugated linoleic acid (CLA). Thorough investigation, including liver biopsy, revealed no other cause of hepatotoxicity. In the last few years, a considerable number of reports have been published on toxic hepatitis, associated with non-conventional products, attributed with weight-reducing properties. We emphasize the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss, as all that is “natural” may not always be healthy. Only one report of CLA-induced toxic hepatitis is related in the medical literature.</p></span>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 750 "Ancho" => 2074 "Tamanyo" => 346437 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Biopsy shows massive hepatic necrosis suggesting toxic liver damage.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scientific Opinion on the substantiation of health claims related to conjugated linoleic acid (CLA) isomers and contribution to the maintenance or achievement of a normal body weight (ID 686, 726, 1516, 1518, 2892, 3165), increase in lean body mass (ID 498, 731), increase in insulin sensitivity (ID 1517), protection of DNA, proteins and lipids from oxidative damage (ID 564, 1937), and contribution to immune defences by stimulation of production of protective antibodies in response to vaccination (ID 687, 1519) pursuant to Article 13(1) of Regulation (EC) No 1924/2006" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "EFSA J" "fecha" => "2010" "volumen" => "8" "paginaInicial" => "1794" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 20 | 26 | 46 |
| 2024 September | 43 | 20 | 63 |
| 2024 August | 21 | 14 | 35 |
| 2024 July | 39 | 11 | 50 |
| 2024 June | 21 | 3 | 24 |
| 2024 May | 13 | 2 | 15 |
| 2024 April | 27 | 4 | 31 |
| 2024 March | 35 | 3 | 38 |
| 2024 February | 25 | 7 | 32 |
| 2024 January | 19 | 5 | 24 |
| 2023 December | 21 | 5 | 26 |
| 2023 November | 21 | 8 | 29 |
| 2023 October | 22 | 3 | 25 |
| 2023 September | 7 | 2 | 9 |
| 2023 August | 12 | 2 | 14 |
| 2023 July | 9 | 3 | 12 |
| 2023 June | 12 | 2 | 14 |
| 2023 May | 34 | 8 | 42 |
| 2023 April | 17 | 2 | 19 |
| 2023 March | 15 | 4 | 19 |
| 2023 February | 12 | 1 | 13 |
| 2023 January | 5 | 6 | 11 |
| 2022 December | 15 | 5 | 20 |
| 2022 November | 12 | 4 | 16 |
| 2022 October | 5 | 7 | 12 |
| 2022 September | 13 | 6 | 19 |
| 2022 August | 13 | 7 | 20 |
| 2022 July | 11 | 6 | 17 |
| 2022 June | 6 | 7 | 13 |
| 2022 May | 10 | 6 | 16 |
| 2022 April | 15 | 7 | 22 |
| 2022 March | 14 | 9 | 23 |
| 2022 February | 27 | 7 | 34 |
| 2022 January | 42 | 10 | 52 |
| 2021 December | 21 | 7 | 28 |
| 2021 November | 20 | 12 | 32 |
| 2021 October | 33 | 18 | 51 |
| 2021 September | 22 | 8 | 30 |
| 2021 August | 7 | 5 | 12 |
| 2021 July | 7 | 8 | 15 |
| 2021 June | 6 | 8 | 14 |
| 2021 May | 13 | 8 | 21 |
| 2021 April | 16 | 11 | 27 |
| 2021 March | 7 | 4 | 11 |
| 2021 February | 3 | 4 | 7 |
| 2021 January | 2 | 5 | 7 |
| 2020 December | 4 | 6 | 10 |
| 2020 November | 3 | 4 | 7 |
| 2020 October | 4 | 5 | 9 |
| 2020 September | 4 | 3 | 7 |
| 2020 August | 4 | 2 | 6 |
| 2020 July | 3 | 3 | 6 |
| 2020 June | 3 | 2 | 5 |
| 2020 May | 2 | 2 | 4 |
| 2020 April | 2 | 2 | 4 |
| 2020 March | 6 | 2 | 8 |
| 2020 February | 1 | 2 | 3 |
| 2020 January | 1 | 3 | 4 |
| 2019 December | 2 | 8 | 10 |
| 2019 November | 4 | 3 | 7 |
| 2019 September | 1 | 2 | 3 |
| 2019 August | 2 | 1 | 3 |
| 2019 July | 0 | 5 | 5 |
| 2019 June | 2 | 7 | 9 |
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