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Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria.

Frei P, Minder EI, Corti N, Muellhaupt B, Geier A, Adams H, Dutertre JP, Rudiger A, Dutkowski P, Maggiorini M, Ganter CC - Case Rep Gastroenterol (2012)

Bottom Line: The patient recovered within a short time.The literature and recommendations in case of heme arginate overdose are summarized.Knowledge of a potentially fatal course is important for the management of future cases.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.

ABSTRACT
In acute attacks of acute intermittent porphyria, the mainstay of treatment is glucose and heme arginate administration. We present the case of a 58-year-old patient with acute liver failure requiring urgent liver transplantation after erroneous 6-fold overdose of heme arginate during an acute attack. As recommended in the product information, albumin and charcoal were administered and hemodiafiltration was started, which could not prevent acute liver failure, requiring super-urgent liver transplantation after 6 days. The explanted liver showed no preexisting liver cirrhosis, but signs of subacute liver injury and starting regeneration. The patient recovered within a short time. A literature review revealed four poorly documented cases of potential hepatic and/or renal toxicity of hematin or heme arginate. This is the first published case report of acute liver failure requiring super-urgent liver transplantation after accidental heme arginate overdose. The literature and recommendations in case of heme arginate overdose are summarized. Knowledge of a potentially fatal course is important for the management of future cases. If acute liver failure in case of heme arginate overdose is progressive, super-urgent liver transplantation has to be evaluated.

No MeSH data available.


Related in: MedlinePlus

Histopathological examination of the liver explant was suggestive of subacute toxic liver injury with little signs of histological recovery and without signs of underlying chronic liver disease such as fibrosis or cirrhosis. a Hypoplastic and hyperplastic hepatocytes. b Resorptive inflammation and ductular proliferation. c Ductular proliferates as a sign of regeneration (cytokeratin 7 immunostaining). d No preexisting fibrous septa or cirrhosis (Elastica van Gieson staining). e Sinusoidal fibrous septa seen as a sign of reparation (Sirius staining). Scale bars represent 200 µm in panels a–d and 100 µm in panel e.
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Figure 2: Histopathological examination of the liver explant was suggestive of subacute toxic liver injury with little signs of histological recovery and without signs of underlying chronic liver disease such as fibrosis or cirrhosis. a Hypoplastic and hyperplastic hepatocytes. b Resorptive inflammation and ductular proliferation. c Ductular proliferates as a sign of regeneration (cytokeratin 7 immunostaining). d No preexisting fibrous septa or cirrhosis (Elastica van Gieson staining). e Sinusoidal fibrous septa seen as a sign of reparation (Sirius staining). Scale bars represent 200 µm in panels a–d and 100 µm in panel e.

Mentions: The patient was transferred to the intensive care unit. As recommended in the product information, intravenous infusions of glucose 20% and of albumin (20 g repeatedly) were given to bind free hemin, and repetitive oral charcoal suspensions (a total of 90 g from 3.5 h to 48 h after overdose) were administered to interrupt the enterohepatic recirculation of hemin. Nevertheless, the patient developed acute liver failure, with rapidly rising transaminases and worsening coagulation (fig. 1). With substitution of glucose 50%, no hypoglycemia was apparent. The patient became oliguric, and continuous venovenous hemodiafiltration (CVVHDF) was started. The patient remained hemodynamically stable. Viral hepatitis was excluded. During the 2 days before heme arginate overdose, the patient had received daily doses of 10,000 U of subcutaneous heparin, 60 mg propranolol, 2,400 mg sevelamer, 600 mg aspirin, 3.75 mg midazolam, 15 mg oxazepam and 0–2 g paracetamol, with a maximum dose of paracetamol of 3 g given on the day heme arginate was initiated. Thereafter, paracetamol was discontinued, with no paracetamol detectable in the serum 25 h after the overdose. Treatment with sevelamer and propranolol was continued and the patient was given 10 mg metoclopramide, macrogol, lactulose, 1 g metamizole and 10–12 mg morphine daily and a single dose of 10 mg of vitamin K. No coagulation products had to be given. After 48 h, the patient was transferred to our tertiary care hospital due to deteriorating acute liver failure and listed for super-urgent liver transplantation. Coagulation was worsening (coagulation factor V unmeasurable), CVVHDF was being continued due to anuric renal failure, and the patient developed encephalopathy grade I-II. 62 h after the overdose, transaminases peaked and coagulation improved (coagulation factor V 12%), suggesting spontaneous liver recovery. However, on the 5th day, liver function again deteriorated, with worsening coagulation and deteriorating encephalopathy necessitating intubation and mechanical ventilation. After 6 days, a liver graft from a deceased donor was available and the patient was transplanted. Histopathological analysis of the liver explant revealed subacute toxic liver injury without signs of underlying liver disease (fig. 2). One year later, the patient is in good condition and the AIP seems to have been cured by the liver transplantation, although she is still on intermittent hemodialysis.


Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria.

Frei P, Minder EI, Corti N, Muellhaupt B, Geier A, Adams H, Dutertre JP, Rudiger A, Dutkowski P, Maggiorini M, Ganter CC - Case Rep Gastroenterol (2012)

Histopathological examination of the liver explant was suggestive of subacute toxic liver injury with little signs of histological recovery and without signs of underlying chronic liver disease such as fibrosis or cirrhosis. a Hypoplastic and hyperplastic hepatocytes. b Resorptive inflammation and ductular proliferation. c Ductular proliferates as a sign of regeneration (cytokeratin 7 immunostaining). d No preexisting fibrous septa or cirrhosis (Elastica van Gieson staining). e Sinusoidal fibrous septa seen as a sign of reparation (Sirius staining). Scale bars represent 200 µm in panels a–d and 100 µm in panel e.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3362186&req=5

Figure 2: Histopathological examination of the liver explant was suggestive of subacute toxic liver injury with little signs of histological recovery and without signs of underlying chronic liver disease such as fibrosis or cirrhosis. a Hypoplastic and hyperplastic hepatocytes. b Resorptive inflammation and ductular proliferation. c Ductular proliferates as a sign of regeneration (cytokeratin 7 immunostaining). d No preexisting fibrous septa or cirrhosis (Elastica van Gieson staining). e Sinusoidal fibrous septa seen as a sign of reparation (Sirius staining). Scale bars represent 200 µm in panels a–d and 100 µm in panel e.
Mentions: The patient was transferred to the intensive care unit. As recommended in the product information, intravenous infusions of glucose 20% and of albumin (20 g repeatedly) were given to bind free hemin, and repetitive oral charcoal suspensions (a total of 90 g from 3.5 h to 48 h after overdose) were administered to interrupt the enterohepatic recirculation of hemin. Nevertheless, the patient developed acute liver failure, with rapidly rising transaminases and worsening coagulation (fig. 1). With substitution of glucose 50%, no hypoglycemia was apparent. The patient became oliguric, and continuous venovenous hemodiafiltration (CVVHDF) was started. The patient remained hemodynamically stable. Viral hepatitis was excluded. During the 2 days before heme arginate overdose, the patient had received daily doses of 10,000 U of subcutaneous heparin, 60 mg propranolol, 2,400 mg sevelamer, 600 mg aspirin, 3.75 mg midazolam, 15 mg oxazepam and 0–2 g paracetamol, with a maximum dose of paracetamol of 3 g given on the day heme arginate was initiated. Thereafter, paracetamol was discontinued, with no paracetamol detectable in the serum 25 h after the overdose. Treatment with sevelamer and propranolol was continued and the patient was given 10 mg metoclopramide, macrogol, lactulose, 1 g metamizole and 10–12 mg morphine daily and a single dose of 10 mg of vitamin K. No coagulation products had to be given. After 48 h, the patient was transferred to our tertiary care hospital due to deteriorating acute liver failure and listed for super-urgent liver transplantation. Coagulation was worsening (coagulation factor V unmeasurable), CVVHDF was being continued due to anuric renal failure, and the patient developed encephalopathy grade I-II. 62 h after the overdose, transaminases peaked and coagulation improved (coagulation factor V 12%), suggesting spontaneous liver recovery. However, on the 5th day, liver function again deteriorated, with worsening coagulation and deteriorating encephalopathy necessitating intubation and mechanical ventilation. After 6 days, a liver graft from a deceased donor was available and the patient was transplanted. Histopathological analysis of the liver explant revealed subacute toxic liver injury without signs of underlying liver disease (fig. 2). One year later, the patient is in good condition and the AIP seems to have been cured by the liver transplantation, although she is still on intermittent hemodialysis.

Bottom Line: The patient recovered within a short time.The literature and recommendations in case of heme arginate overdose are summarized.Knowledge of a potentially fatal course is important for the management of future cases.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.

ABSTRACT
In acute attacks of acute intermittent porphyria, the mainstay of treatment is glucose and heme arginate administration. We present the case of a 58-year-old patient with acute liver failure requiring urgent liver transplantation after erroneous 6-fold overdose of heme arginate during an acute attack. As recommended in the product information, albumin and charcoal were administered and hemodiafiltration was started, which could not prevent acute liver failure, requiring super-urgent liver transplantation after 6 days. The explanted liver showed no preexisting liver cirrhosis, but signs of subacute liver injury and starting regeneration. The patient recovered within a short time. A literature review revealed four poorly documented cases of potential hepatic and/or renal toxicity of hematin or heme arginate. This is the first published case report of acute liver failure requiring super-urgent liver transplantation after accidental heme arginate overdose. The literature and recommendations in case of heme arginate overdose are summarized. Knowledge of a potentially fatal course is important for the management of future cases. If acute liver failure in case of heme arginate overdose is progressive, super-urgent liver transplantation has to be evaluated.

No MeSH data available.


Related in: MedlinePlus