<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJGas</journal-id><journal-title-group><journal-title>Open Journal of Gastroenterology</journal-title></journal-title-group><issn pub-type="epub">2163-9450</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojgas.2024.145018</article-id><article-id pub-id-type="publisher-id">OJGas-133281</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Fulminant Hepatitis Associated with Chronic Consumption of 3,4-Methylenedioxy-Methamphetamine; Case Report
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ulises</surname><given-names>Solis Gomez</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gustavo</surname><given-names>Adolfo Hern&amp;#225;ndez Valdez</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Juan</surname><given-names>Antonio Contreras Escamilla</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ivan</surname><given-names>Alejandro Medina Jimenez</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jorge</surname><given-names>Morales Rojas</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jocelyn</surname><given-names>Nataly Quintero Melendez</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Marco</surname><given-names>Antonio Gonz&amp;#225;lez Villar</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Department of Internal Medicine, ISSSTE APP General Hospital of Tepic, Tepic, Nayarit, Mexico</addr-line></aff><pub-date pub-type="epub"><day>11</day><month>05</month><year>2024</year></pub-date><volume>14</volume><issue>05</issue><fpage>161</fpage><lpage>166</lpage><history><date date-type="received"><day>3,</day>	<month>April</month>	<year>2024</year></date><date date-type="rev-recd"><day>20,</day>	<month>May</month>	<year>2024</year>	</date><date date-type="accepted"><day>23,</day>	<month>May</month>	<year>2024</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).
 
</p></abstract><kwd-group><kwd>Fulminant Hepatitis</kwd><kwd> Acute Liver Failure</kwd><kwd> Methamphetamine</kwd><kwd> Severe Acute Liver Failure in a User of Drugs of Abuse</kwd><kwd> Hepatology</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Amphetamines are designer drugs, among the best known today, which are known to have originally been widely used in academic, industrial and medical settings [<xref ref-type="bibr" rid="scirp.133281-ref1">1</xref>] . Of these compounds, the most used is 3,4-methylendioxy-methamphetamine (MDMA) and 3,4-methylenedioxy-amphetmine (MDA), MDMA was first synthesized in 1914 as an appetite suppressant, but it was not until 1960 that it began to be used as a recreational drug in the US. And in 1990 in the rest of the world [<xref ref-type="bibr" rid="scirp.133281-ref2">2</xref>] . With the passage of time, its long-term adverse effects such as damage to the central nervous system, heart, kidney and hepatotoxicity began to be discovered. Hepatotoxicity, although the exact mechanism is unknown, is believed to be due to multiple mechanisms, among the most investigated is the interaction of amphetamines and monoaminergic receptors, mainly adrenergic, which have a vasoconstrictor effect at the level of arterial smooth muscle and damage. directly to the vascular endothelium [<xref ref-type="bibr" rid="scirp.133281-ref1">1</xref>] . Likewise, the stimulation of the release of vasopressin is also known, which with the vasoconstrictor effect could generate ischemia at the liver level and therefore cellular damage that, if perpetuated, could cause liver failure [<xref ref-type="bibr" rid="scirp.133281-ref3">3</xref>] .</p><p>This hepatotoxicity in a few cases has been associated with acute liver failure or also called fulminant hepatitis, which has a high mortality rate, so knowing this type of aspects is of great help in the prevention of addictions and consequences in the short and long term.</p></sec><sec id="s2"><title>2. Clinical Case</title><p>Below is a 39-year-old patient. He went to the emergency room due to sudden dyspnea associated with abdominal pain in the region of the right upper quadrant, as well as mixed liver damage (hepatocellular and cholestatic).</p><p>As important antecedents, he refers to positive smoking from the age of 15 to the present, social alcoholism, sporadic use of Marijuana and daily use of MDMA for 10 years, negative medical history for blood transfusions, use of allopathic or homeopathic drugs, no risky sexual relations as well as a negative oncological history.</p><p>During his clinical evaluation, he presented jaundice in the integuments and skin, as well as pruritus and generalized weakness.</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Liver biochemical parameters during patient hospitalization</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >Admission</th><th align="center" valign="middle" >Day 2</th><th align="center" valign="middle" >Day 3</th><th align="center" valign="middle" >Day 4</th><th align="center" valign="middle" >Day 5</th><th align="center" valign="middle" >Day 6</th></tr></thead><tr><td align="center" valign="middle" >AST (U/L)</td><td align="center" valign="middle" >78</td><td align="center" valign="middle" >144</td><td align="center" valign="middle" >345</td><td align="center" valign="middle" >500</td><td align="center" valign="middle" >810</td><td align="center" valign="middle" >1409</td></tr><tr><td align="center" valign="middle" >ALT (U/L)</td><td align="center" valign="middle" >100</td><td align="center" valign="middle" >230</td><td align="center" valign="middle" >370</td><td align="center" valign="middle" >530</td><td align="center" valign="middle" >690</td><td align="center" valign="middle" >787</td></tr><tr><td align="center" valign="middle" >Total bilirubin (mg/dL)</td><td align="center" valign="middle" >1.8</td><td align="center" valign="middle" >2.4</td><td align="center" valign="middle" >5.9</td><td align="center" valign="middle" >8.1</td><td align="center" valign="middle" >13.4</td><td align="center" valign="middle" >17.5</td></tr><tr><td align="center" valign="middle" >GGT (U/L)</td><td align="center" valign="middle" >326</td><td align="center" valign="middle" >450</td><td align="center" valign="middle" >530</td><td align="center" valign="middle" >640</td><td align="center" valign="middle" >820</td><td align="center" valign="middle" >910</td></tr><tr><td align="center" valign="middle" >Alkaline phospfatase (U/L)</td><td align="center" valign="middle" >200</td><td align="center" valign="middle" >370</td><td align="center" valign="middle" >530</td><td align="center" valign="middle" >660</td><td align="center" valign="middle" >740</td><td align="center" valign="middle" >810</td></tr><tr><td align="center" valign="middle" >INR</td><td align="center" valign="middle" >1.4</td><td align="center" valign="middle" >1.7</td><td align="center" valign="middle" >2.8</td><td align="center" valign="middle" >4.10</td><td align="center" valign="middle" >5.20</td><td align="center" valign="middle" >7.15</td></tr></tbody></table></table-wrap><p>AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, GGT: Gammaglutamyl transpeptidase, INR: International normalized index.</p><p>Paraclinical on admission: TGO: 78 U/L, TGP: 100 U/L, GGT: 326 U/L, alkaline phosphatase: 200 U/L, direct bilirubin: 0.73 mg/dL, indirect bilirubin: 1.07 mg/dL, leukocytes: 5.83*10<sup>3</sup>/μL, neutrophils: 2.87*10<sup>3</sup>/μL, hemoglobin: 15.6 g/dL, platelets 239*10<sup>3</sup>/μL, prothrombin time: 16.1 seconds, partial thromboplastin time: 26.9 seconds, INR: 1.4 (<xref ref-type="table" rid="table1">Table 1</xref>).</p><p>Imaging studies: Liver ultrasound: Chronic acalculous cholecystitis, mild ascites, grade 1 hepatic steatosis (<xref ref-type="fig" rid="fig1">Figure 1</xref>, <xref ref-type="fig" rid="fig2">Figure 2</xref>).</p><p>A few days after admission, there was an acute increase in bilirubin and transaminases, as well as an INR greater than 1.5, as well as grade IV hepatic encephalopathy, which is why it is classified as acute liver failure. Due to the above and to clarify the etiology of the condition, the following laboratories are performed: Viral serologies (HBV, HAV, HCV, Epstein-Barr virus, cytomegalovirus and HIV), as well as screening for autoantibodies (AMA, ANA, AAML, LKM), were negative. Due to the above and the only history of MDMA consumption, we made the diagnosis of acute toxic hepatitis.</p><p>Later, during his evolution, the patient presents hypotension, tachypnea, as well as severe desaturation, which is why intubation and the start of assisted mechanical ventilation are continued. Renal replacement therapy (hemodialysis) is performed due to acute kidney injury as well as initiation of dobutamine and norepinephrine due to association with a mixed state of shock (cardiogenic and hypovolemic). General measures and support are initiated to continue the evolution and possibility of a liver transplant. However, due to his serious condition, the patient died 48 hours after the start of assisted mechanical ventilation.</p></sec><sec id="s3"><title>3. Discussion</title><p>Recreational use of 3,4-methylenedioxymethamphetamine (MDMA) among young people is very popular as it increases psychomotor activity, ease of communication, as well as increasing alertness, etc. [<xref ref-type="bibr" rid="scirp.133281-ref4">4</xref>] . In relation to chronic diseases, damage to the nervous and cardiac systems, rhabdomyolysis and hyperthermia are known [<xref ref-type="bibr" rid="scirp.133281-ref5">5</xref>] . In the case of hepatotoxicity due to MDMA, this is multifactorial, although it has been described that the metabolism of MDMA is metabolized by two main pathways: the first is N-desakilation, deamination and oxidation and the second is demethylation followed by methylation catalyzed with catechol-O-methyltransferase, the latter involves a CYP2D6 isoenzyme of the cytochrome P450 system, which can form inhibitory complexes with MDMA molecules and thus potential toxicity [<xref ref-type="bibr" rid="scirp.133281-ref3">3</xref>] .</p><p>Hypersensitivity reactions, direct hepatocellular damage or its adulterants, ischemia have also been described, the latter being very important due to its effect on monoaminergic receptors, mainly the adrenergic receptor, which has a vasoconstrictive effect at the level of arterial smooth muscle, and direct damage to the hepatic endothelium, as well as by secretion of vasopressin, which will have a similar effect [<xref ref-type="bibr" rid="scirp.133281-ref6">6</xref>] .</p><p>In the case of our patient, a diagnosis of acute liver failure or also called fulminant type was made since he completed a period of less than 26 weeks, he was not known to have previous liver disease, he had elevated liver enzymes associated with coagulopathy (INR &gt; 1.5) and alterations in mental status (encephalopathy) [<xref ref-type="bibr" rid="scirp.133281-ref7">7</xref>] .With the description of the time elapsed between the appearance of jaundice and the development of encephalopathy, as acute according to the O’Grady Classification [<xref ref-type="bibr" rid="scirp.133281-ref8">8</xref>] . The role of liver biopsy is limited by hemodynamic instability and associated coagulopathy, in addition to not having pathognomonic signs that could suggest the origin of 3,4-methylenedioxymethamphetamine (MDMA) consumption.</p><p>Due to the multiple causes of acute liver failure, which is associated with 3,4-methylenedioxymethamphetamine (MDMA) toxicity, other causes of hepatotoxicity such as medications, foods, infectious diseases, thrombotic events, as well as alcohol, will have to be ruled out. In the case of our patient, they were discarded [<xref ref-type="bibr" rid="scirp.133281-ref6">6</xref>] .</p><p>Although there are international guidelines for treatment of acute liver failure, treatment usually consists of supportive measures as well as treatment of the condition that is causing the liver failure. In relation to 3,4-methylenedioxymethamphetamine (MDMA) poisoning, there is no standardized treatment, only liver transplantation, and recently research has been done on molecular sorbent recirculation (MARS) or liver dialysis, which consists of two circuits of recirculation one with albumin with high affinity to toxins and the second circuit to clean the albumin solution and therefore the toxins [<xref ref-type="bibr" rid="scirp.133281-ref9">9</xref>] .</p><p>MDMA consumption has grown worldwide and is associated with low economic status, dysfunctional families, psychiatric disorders, etc. Therefore, it is very important for health ministries to have social programs for addictions, as well as reintegration programs in educational, cultural, as well as social activities.</p></sec><sec id="s4"><title>4. Conclusions</title><p>3,4-methylenedioxymethamphetamine (MDMA) is a currently fashionable drug of abuse with a high incidence in young people, therefore, knowing about acute and chronic complications is of utmost importance to raise awareness in society so that they know the risks of its consumption and programs are made for its prevention.</p><p>Early attention to this type of pathology in intensive care units, as well as centers specialized in liver transplantation, could increase survival. In recent years, liver support devices such as MARS have been of great help as a bridging therapy for liver transplantation or as an opportunity to recover liver function and thus avoid transplantation. Although these types of therapies are still under investigation and their use is limited even in several countries.</p></sec><sec id="s5"><title>5. Ethical Considerations</title><p>The authors declare that they have met all ethical responsibilities regarding data protection, right to privacy and informed consent.</p><p>Authorization from the institution’s ethics committee is not necessary since at no time do they fail to comply or violate patient anonymity rules, nor is any experimental procedure performed that puts the patient’s integrity at risk.</p><p>The authors declare that this article does not contain personal information that would allow the patient described to be identified, which makes the patient’s informed consent unnecessary for the publication of the article.</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest regarding the publication of this paper.</p></sec><sec id="s7"><title>Cite this paper</title><p>Gomez, U.S., Valdez, G.A.H., Escamilla, J.A.C., Jimenez, I.A.M., Rojas, J.M., Melendez, J.N.Q. and Villar, M.A.G. (2024) Fulminant Hepatitis Associated with Chronic Consumption of 3,4-Methylenedioxy-Methamphetamine; Case Report. Open Journal of Gastroenterology, 14, 161-166. https://doi.org/10.4236/ojgas.2024.145018</p></sec></body><back><ref-list><title>References</title><ref id="scirp.133281-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Luethi, D. and Liechti, M.E. (2020) Designer Drugs: Mechanism of Action and Adverse Effects. &lt;i&gt;Archives &lt;/i&gt;&lt;i&gt;o&lt;/i&gt;&lt;i&gt;f Toxicology&lt;/i&gt;, 94, 1085-1133. &lt;br&gt;https://doi.org/10.1007/s00204-020-02693-7 </mixed-citation></ref><ref id="scirp.133281-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">Christophersen, A.S. 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