Environmental Disease

: 2022  |  Volume : 7  |  Issue : 4  |  Page : 102--105

A case of fatal liver failure due to chronic environmental exposure of copper in a child

Utpal Sutaria, Rohan Modi, Aarti Solanki, Nehal Patel 
 Department of Pediatrics, GMERS Medical College and Sola Civil Hospital, Ahmedabad, Gujarat, India

Correspondence Address:
Nehal Patel
Department of Pediatrics, GMERS Medical College and Sola Civil Hospital, Ahmedabad - 380 060, Gujarat


Chronic liver damage followed by copper toxicity is very rare in pediatric population. This case report describes a 9-year-old child with acute liver failure as the presentation of copper toxicity due to chronic environmental exposure as a part of an occupational hazard. If not intervened in the early stage, the outcome is always lethal. Therefore, it is recommended to rule out heavy metal toxicity like copper as a cause of liver damage for any case of acute or chronic liver failure after ruling out the common infectious and inflammatory causes.

How to cite this article:
Sutaria U, Modi R, Solanki A, Patel N. A case of fatal liver failure due to chronic environmental exposure of copper in a child.Environ Dis 2022;7:102-105

How to cite this URL:
Sutaria U, Modi R, Solanki A, Patel N. A case of fatal liver failure due to chronic environmental exposure of copper in a child. Environ Dis [serial online] 2022 [cited 2023 Jun 3 ];7:102-105
Available from: http://www.environmentmed.org/text.asp?2022/7/4/102/365626

Full Text


The presence of harmful environmental exposures, which disproportionately affects low- and middle-income countries, contributes to >25% of deaths and diseases worldwide and dramatically affects the child's neurodevelopmental status. Copper is a trace element found in high concentrations in the brain, liver, and kidney. However, the bone and muscle contain more than half of the copper in the body. The gastrointestinal (GI) tract is a major regulator of copper homeostasis. Copper is required as an important catalytic cofactor in redox chemistry for many proteins, while excess free copper ions can cause damage to cellular components by not only oxidative stress but also induce DNA damage and reduced cell proliferation. Copper toxicosis can be classified as primary when it results from an inherited metabolic defect and secondary when it results from high intake or increased absorption or reduced excretion. It is a reddish metal naturally present in soil, water, rock, sediment, and air. Copper toxicity can be caused by consuming acidic food cooked in uncoated copper cookware, exposure to excess copper in drinking water, cutaneous contact, breathing contaminated air, or other environmental sources. Copper can enter into environment from factories that make or use copper compounds. Here, we present a case report of a child with symptoms of copper toxicity due to chronic environmental exposure.

 Case Report

A 9-year-old male child with no significant medical history presented to the pediatric emergency department with jaundice and vomiting since 1 month, abdominal distension for 15 days, and bleeding from mouth, nose, urine, and stool for the past 2 days.

On detailed examination, the child had active bleeding from the nose and mouth, altered sensorium, tachycardia, tachypnea, low pulse volume, and hypotension (blood pressure of 90/60 mmHg). Yellowish discoloration of the skin and sclera was evident. The child had gross abdominal distension with hepatosplenomegaly and ascites [Figure 1]a. The infectious causes of acute hepatitis and bacterial sepsis were ruled out by appropriate investigations as the child presented with the features of acute liver failure with hepatic encephalopathy. The patient came to our hospital from a nearby state where his father was working as a factory laborer. Initially, they took treatment from the nonregistered medical practitioners in the nearby area who prescribed some Ayurvedic medicines and some eye drops for yellow discoloration of the sclera. As GI bleed with altered sensorium developed, the patient was referred to our hospital. As the child had greenish-black discoloration of nails and plantar surface of his feet, we reviewed the place of residence of the child. As parents were working in a copper chloride manufacturing factory, the whole family was residing in that industrial area for the past few years. Hence, we suspected chronic copper poisoning as an occupational hazard due to chronic exposure on playing in copper-containing industrial soil [Figure 1]b and [Figure 1]c. His ophthalmological examination does not reveal any Kayser–Fleischer (KF) ring. We were not able to measure copper in the patient's drinking water as the area was very far from our hospital.{Figure 1}

As initial treatment, intravenous (IV) fluid, inotropic support, ventilator support, IV antibiotics, and injection Vitamin K were given. Fresh frozen plasma and packed cell volume transfusion were given in view of altered coagulation profile, continuing blood loss, and severe anemia. The child had hyperbilirubinemia (total bilirubin – 42.6 mg/dl with direct bilirubin – 30.60 mg/dl with raised transaminase (SGPT –300 U/L), hypoalbuminemia (s. albumin – 2.4 g/dl), severe anemia (HB – 4.7 g/dl), leukocytosis (total leukocyte counts – 21,500), and thrombocytopenia (platelet count – 85,000). On further investigation, HbsAg was negative with normal S. Ceruloplasmin – 23.73 mg/dl (22–50 mg/dl). The copper toxicity-specific investigation showed a high level of serum total copper – 376 μg/dl (80–180) and 24 h urinary copper – 292 μg (15–60). The pediatric end-stage liver disease score for the patient was 52.0 (10* (0.480*bilirubin) +1.857*INR-0.687(albumin) +0.436), suggestive of 66% of 1 year waiting list survival for liver transplant and 84.6% of 1 year posttransplant survival.[1] The NAZER index was 12 (>9), suggestive of immediate liver transplantation required.[2] The possible treatment options were zinc chelation, plasmapheresis, and IV chelators. We were not able to give zinc, D-penicillamine, or trientine-like chelation therapy orally due to continuous hemorrhagic gastric aspirates since the admission. Plasmapheresis was not available at our institute, and it was only available for the children more than 12 years of age at another government institute in our city. IV chelators such as sodium dimercaptosulfonate or intramuscular chelators like dimercaprol were used in many heavy metal poisoning. However, due to the unavailability of such drug in our hospital and unaffordability of the patient, we were not able to use it as a possible treatment in the patient. Unfortunately, the child expired after 2 days.

The yellow-green discoloration of the gross specimen of postmortem liver biopsy [Figure 2]a and also of urine [Figure 2]b was also suggestive of chronic copper deposition on the liver. The histopathology findings of the liver biopsy were suggestive of hemosiderin deposition with inflammatory infiltration with hepatocytes necrosis [Figure 2]c and [Figure 2]d. The dry copper weight estimation of that biopsy tissue also had a high copper concentration of 193 μg/gm (0–45). The estimation of free copper was 301.26 as per the calculation provided by Hoogenraad and EASL 2012.[3],[4]{Figure 2}


Copper is an essential element for the human body. It is a key element for various physiological cellular functions such as oxidative stress protection, elimination of free radicals, cardiovascular function, and synthesis of neurotransmitters and hormones. Excessive free copper accumulates in the body tissue and causes severe cell damage mainly through free radical reactions.[5]

The recommended daily copper intake is between 0.6 and 1.6 mg/day for a normal adult.[6] The sources of copper are nuts, legumes, beans, shellfish, and liver. A high amount of copper can enter into the body through drinking water and eating food in copper vessels.

Copper gets absorbed from the stomach and small intestine and is transported to the liver through albumin. After hepatic uptake, copper gets incorporated into various copper-containing enzymes or into ceruloplasmin and then exported to blood. Copper in the cytoplasm is bound to metallothionein, which is a metal-binding protein. Excess copper is released into the bile and excreted through feces.[7]

Excessive hepatic copper accumulation causes hepatotoxicity mainly through oxidative damage to lysosomal lipids and results in chronic inflammatory changes. Liver damage can present with jaundice, hypoalbuminemia, bleeding manifestations, hepatomegaly, and acute liver failure.[8]

Acute copper poisoning generally presents with GI symptoms such as vomiting, abdominal pain, GI bleeding, ulceration, and perforation in severe cases. Other uncommon symptoms of copper ingestion are hemolytic anemia, acute renal failure, rhabdomyolysis, and methemoglobinemia.[9]

Copper levels can be measured in body fluids, tissues, and excreta such as blood, urine, stools, hair, and liver tissue. KF ring can be identified through slit-lamp examination in excessive copper accumulation.[10] In most untreated patients, it is elevated above 200 microgram/L. The serum nonceruloplasmin copper (or free copper) concentration may be elevated in acute liver failure of any etiology, in chronic cholestasis, and cases of copper intoxication. The major problem with free copper as a diagnostic test for such conditions is that it is dependent on the adequacy of the methods for measuring both serum copper and ceruloplasmin. It is of more value in monitoring pharmacotherapy than in diagnosis.[4]

In our case, the child presented with acute liver failure with symptoms of jaundice, ascites, bleeding from the mouth and nose and upper GI track, hematuria, and hepatosplenomegaly. After ruling out the common infections and inflammatory causes for acute liver failure, on background of the occupational history of parents, we suspected for copper toxicity and evaluated for the same. Copper toxicity is rare in pediatric patients, but can present with acute or chronic liver disease as in our case.

The management of acute copper poisoning is supportive care, copper chelation therapy, fluid resuscitation, replacement of ongoing losses, and symptomatic management.[11] Important management is copper chelation. Available chelators are oral D-penicillamine, trientine, zinc, IV sodium dimercaptosulfonate, and intramuscular dimercaprol. Plasmapheresis can be used as one of the alternative therapies to remove excess free copper from the blood. The most commonly used chelator is D-penicillamine and zinc. The recommended dose is 20 mg/kg/day to the maximum of 1,500 mg/day. The mechanism of action of D-penicillamine is by inducing hepatic metallothionein synthesis, inducing cupriuresis, and reducing fibrosis. Trientine is given at a dose of 20 mg/kg/day to the maximum of 1,500 mg/day similarly as DPA. The role of copper chelators in non-Wilson's copper disease is controversial, but still, there are some studies that suggested improvement in the liver functions after introducing the copper chelators.[12]


Chronic exposure to environmental copper can lead to acute liver failure in children. Occupational exposure leading to copper toxicity is rare but fatal.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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