Acute kidney failure caused by paracetamol poisoning

Paracetamol poisoning is manifested by hepatotoxicity, but acute renal failure is very rare, especially when there is no fulminant hepatic damage with encephalopathy or severe haemodynamic alterations. We present here the case of a 22-year-old woman who presented with acute renal failure after the ingestion of 11.5 g of acetaminophen. The clinical course and laboratory data were consistent with tubular necrosis. The patient required hemodialysis, but finally renal function returned to normal. The acetaminophen pharmacology and the differential diagnosis of acute azotemia in paracetamol overdosage are reviewed.     

Potentiation of Acetaminophen Hepatotoxicity by Phenytoin,Leading to Liver Transplantation

We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the “nontoxic” range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.     

Hemorrhagic Pancreatitis Associated with Acetaminophen Overdose

A 19-yr-old man ingested 25 g of acetaminophen in a suicide attempt. Twenty-one hours after the ingestion the plasma acetaminophen level was potentially hepatoxic at 62 micrograms/ml. The toxicology screen was negative for all other drugs. Thirty-six hours after admission the patient developed an acute abdomen with a serum amylase of 1500 IU. Peritoneal lavage revealed a grossly hemorrhagic fluid. Exploratory laparotomy revealed necrotic pancreatitis. Hepatoxicity with the peak SGOT greater than 2000 IU and a mild renal toxicity with the creatinine of 1.9 mg/dl occurred despite late initiation of treatment with n-acetylcysteine. No other etiology for the pancreatitis was found. Peritoneal irrigation was continuously performed through a surgically placed dialysis catheter. Pancreatitis associated with acetaminophen overdose has been reported twice in the past. Although the pathophysiology of the pancreatic injury is obscure, the lack of other etiological factors and temporal association of the pancreatitis with acetaminophen-induced hepatic and renal toxicity suggest a causal relationship.     

Early metabolic acidosis and coma after acetaminophen ingestion

Metabolic acidosis and coma may develop in patients who experience severe hepatic injury after acetaminophen poisoning. The onset of acidosis and coma soon after acetaminophen overdose, but preceding manifest hepatic injury, contrasts with the typical course of poisoning. This pattern has been reported in a limited number of cases. Coingestions and the rare occurrence of these findings after an overdose have engendered controversy as to whether acetaminophen alone is the cause of early coma and acidosis. We describe 4 separate overdoses among 3 patients who arrived at the emergency department comatose with a metabolic acidosis soon after ingesting large amounts of acetaminophen without evidence of toxic liver injury. Our cases support the view that early metabolic acidosis with coma does indeed occur after acetaminophen poisoning, independent of hepatic failure or its complications.     

Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 +/- 1.18 mmol/L vs. 0.68 +/- 0.22 mmol/L, P <.001) as well as 72 to 96 hours after overdose (2.12 +/- 0.22 mmol/L vs. 0.59 +/- 0.23 mmol/L, P <.001). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than the KCH criteria, and it identified patients significantly earlier after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P <.05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated with renal dysfunction (R =.55; P =.02). In conclusion, hyperphosphatemia after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering of serum phosphate.     

Hepatitis A-induced diabetes mellitus, acute renal failure, and liver failure.

A 38-year-old otherwise healthy man presented with hepatic failure (aspartate aminotransferase of 7212 U/L, alanine aminotransferase of 6629 U/L, total and direct bilirubin of 10.7 mg/dL) and acute renal failure (creatinine of 11.6 mg/dL and blood urea nitrogen of 42 mg/dL), which required hemodialysis when the creatinine increased to 21 mg/dL, with a blood urea nitrogen of 115 mg/dL, and the patient became oliguric. On admission, this patient also had a lipase of 1833 U/L, amylase of 211 U/L, glucose of 210 mg/dL, and reactive IgM antibody for acute hepatitis A. The hepatitis and acute renal failure resolved in 3 months, but this patient continues to have type II diabetes mellitus 7 years after the hepatitis A infection. This case illustrates that hepatitis A infection may be severe with liver failure, acute renal failure, and permanent diabetes mellitus as sequale of this infection.     

Development of Hepatic Failure Despite Use of Intravenous Acetylcysteine After a Massive Ingestion of Acetaminophen and Diphenhydramine

Acetylcysteine is an antidote used to prevent liver failure after acetaminophen overdose. We report the development of liver failure despite administration of intravenous acetylcysteine in a patient with massive ingestion of an acetaminophen and diphenhydramine combination product. An atypical, delayed, bimodal peak in the serum acetaminophen concentration was observed. This case suggests that individualized dosing of antidotal therapy may be needed for preparations of acetaminophen that result in delayed absorption or after massive overdose.     

Percutaneous ethanol injection for hepatocellular carcinoma originating in the caudate lobe

BACKGROUND/AIMS: Hepatocellular carcinoma originating in the caudate lobe is rare and the treatments for caudate hepatocellular carcinoma were thought difficult, because of its unique location at hepatic resection, or because of complex arterial supply at transcatheter arterial embolization. Percutaneous ethanol injection is an effective treatment for small hepatocellular carcinoma. The aim of this study was to assess the efficacy of percutaneous ethanol injection for hepatocellular carcinoma originating in the caudate lobe. METHODOLOGY: During the past 4 years, 7 patients with 7 hepatocellular carcinomas originating in the caudate lobe underwent percutaneous ethanol injection as a curative treatment. The outcomes of percutaneous ethanol injection and the survival of the 7 patients were evaluated. RESULTS: Percutaneous ethanol injection was successfully carried out with no severe complications in all patients. During follow-up periods local recurrence was noticed in a patient, that was treated with percutaneous ethanol injection again. Four patients had recurrence in other parts of the liver, who were treated with percutaneous ethanol injection alone or percutaneous ethanol injection and transcatheter arterial embolization. Six patients were alive for 12-55 months after percutaneous ethanol injection and 1 patient died of hepatic failure 15 months after the procedure. CONCLUSIONS: Percutaneous ethanol injection was a safe and effective treatment, and it would be an alternative therapy for hepatocellular carcinoma originating in the caudate lobe.     

MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation]

MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation.We report the case of a 30-year-old man who was admitted because of acute liver failure due to longstanding ethanol abuse. On conservative treatment liver function progressively deteriorated and the patient was listed for orthotopic liver transplantation. Because of a rapidly progressive and clinically severe hepatic encephalopathy together with increasing bilirubin levels (maximum 39 mg/dl) we began intermittent extracorporeal detoxification with the Molecular Adsorbent Recycling System (MARS). Under MARS therapy serum bilirubin decreased significantly (to 20 mg/dl after three cycles) and encephalopathy improved rapidly until the patient was completely oriented. No effect of MARS on liver function could be demonstrated. MARS treatment was successfully continued until a cadaver liver became available after 48 days and the patient was transplanted in good clinical and neurological condition and without complications. MARS represents a novel detoxification technique which, in patients with acute liver failure, can successfully replace hepatic detoxification until orthotopic liver transplantation can be performed.     

Lipopolysaccharide-binding protein modulates acetaminophen-induced liver injury in mice

Acetaminophen toxicity is the most common cause of acute liver failure in the United States and Europe. Although much is known about the metabolism of acetaminophen, many questions remain regarding the pathogenesis of liver injury. In this study, we examined the role of lipopolysaccharide-binding protein (LBP), a protein important in mediating cellular response to lipopolysaccharides, by using LBP wild-type and knockout (KO) mice. We found that LBP KO mice were protected from acetaminophen-induced hepatotoxicity. At 350 mg/kg of acetaminophen, LBP KO mice had significantly less liver injury and necrosis than wild-type mice. Repletion studies in LBP KO mice using an LBP-adenoviral construct resulted in significantly more hepatic injury and necrosis after acetaminophen exposure compared with mice receiving the control adenoviral construct. In conclusion, LBP KO mice are protected from toxicity with a decrease in hepatic necrosis following acetaminophen challenge. This suggests a novel role for LBP in modulating acetaminophen-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/O270-9139/suppmat/index.html).     

Anion gap acidosis with hypoglycemia in acetaminophen toxicity

Two case reports of patients with anion gap metabolic lactic acidosis and hypoglycemia are presented. Both patients subsequently died of acute liver failure secondary to acetaminophen hepatotoxicity. The development of type B lactic acidosis with hypoglycemia might have been caused by a deficit in gluconeogenesis secondary to severe hepatic failure and/or a toxic metabolite of acetaminophen. Our findings suggest that acetaminophen toxicity should be considered when lactic acidosis and hypoglycemia are seen.     

Acute liver failure induced by alcohol and paracetamol in an HCV-infected haemophiliac

Paracetamol (acetaminophen) is frequently used by haemophiliacs in the management of acute or chronic pain, primarily due to its lack of adverse effects when taken at therapeutic doses. We describe acute hepatic and renal toxicity of paracetamol in a 36-year-old patient with haemophilia B, chronic hepatitis C and chronic alcohol abuse. Moderate doses of paracetamol (6 g/d for 4 d), taken with therapeutic intent, resulted in life-threatening organ dysfunction which gradually recovered with full supportive care.     

Acute liver failure complicating jejunojejunal intussusception presentation in a gastric bypass patient

Over 200 000 weight loss procedures are performed annually in the United States. Physicians must there-fore be cognizant of the unique array of complications associated with these procedures. We describe a case of jejunojejunal intussusception in a gastric bypass patient who presented with acute liver failure (ALF) due to acetaminophen (APAP) toxicity. Our patient is a 29 year-old female who had undergone Roux-en-Y gastric bypass surgery seven years prior. She was evaluated in the emergency department for confusion. Her family reported a 3-wk history of progressive abdominal pain and vomiting, for which she had ingested 40 acetamin-ophen/oxycodone tablets over the past 2 d. Physical examination showed icteric sclerae, a distended abdomen, and grade Ⅰencephalopathy. She fulfilled the criteria for ALF and was listed for liver transplantation. Abdominal computed tomography scan revealed a je-junojejunal intussusception. She under went emergent exploratory laparotomy and resection of the infarcted intussusceptum and the previous jejunojejunostomy. She had rapid clinical improvement, with decreasing liver enzymes and improved hepatic synthetic function. She had complete resolution of coagulopathy and encephalopathy, and was removed from the liver transplant list. She was discharged home 20 d after hospitalization with normal liver tests. This case demonstrates that acute abdominal catastrophes can potentiate liver injury in the setting of acetaminophen toxicity. Encephalopathy may obscure history and physical exam findings. This case also exemplifies the pitfalls in the management of the bariatric surgery patient and the importance of multispecialty collaboration in patients presenting with organ failure.     

Susceptibility of rat non-alcoholic fatty liver to the acute toxic effect of acetaminophen

Background and Aim: Acetaminophen overdose is the most frequent cause of acute liver failure. Non‐alcoholic fatty liver disease is the most common chronic condition of the liver. The aim was to assess whether non‐alcoholic steatosis sensitizes rat liver to acute toxic effect of acetaminophen. Methods: Male Sprague–Dawley rats were fed a standard diet (ST‐1, 10% kcal fat) and high‐fat gelled diet (HFGD, 71% kcal fat) for 6 weeks and then acetaminophen was applied in a single dose (1 g/kg body weight). Animals were killed 24, 48 and 72 h after acetaminophen administration. Serum biochemistry, activities of mitochondrial complexes, hepatic malondialdehyde, reduced and oxidized glutathione, triacylglycerol and cholesterol contents, and concentrations of serum and liver cytokines (TNF‐α, TGF‐β1) were measured and histopathological samples were prepared. Results: The degree of liver inflammation and hepatocellular necrosis were significantly higher in HFGD fed animals after acetaminophen administration. Serum markers of liver injury were elevated only in acetaminophen treated HFGD fed animals. Concentration of hepatic reduced glutathione and ratio of reduced/oxidized glutathione were decreased in both ST‐1 and HFGD groups at 24 h after acetaminophen application. Mild oxidative stress induced by acetaminophen was confirmed by measurement of malondialdehyde. Liver content of TNF‐α was not significantly altered, but hepatic TGF‐β1 was elevated in acetaminophen treated HFGD rats. We did not observe acetaminophen‐induced changes in activities of respiratory complexes I, II, and IV and activity of caspase‐3. Conclusion: Liver from rats fed HFGD is more susceptible to acute toxic effect of acetaminophen, compared to non‐steatotic liver.     

Acute liver failure

Opinion statement Acute liver failure (ALF) is an uncommon medical emergency whose rapid progression and high mortality demand early diagnosis and expert management, including immediate transfer of any potential case to facilities for intensive care and orthotopic liver transplantation (OLT). All patients with ALF must be screened aggressively for acetaminophen toxicity (history, serum levels, “hyperacute” presentation with renal failure), for other drugs, and viral hepatitis; rare causes of ALF should also be considered. After an acetaminophen overdose, N-acetylcysteine must be given as early as possible, preferably in the emergency room, but any patient with ALF should promptly receive N-acetylcysteine if there is suspicion of acetaminophen toxicity irrespective of the time of ingestion. Supportive care for all patients with ALF includes adequate enteral nutrition, aggressive screening and treatment of infection, prophylactic broad-spectrum antibiotics, and antifungal agents. Sedation with propofol is given for severe agitation or mechanical ventilation. With advanced coma grades, intensive care is needed with hemodynamic monitoring, ventilatory support, continuous renal replacement for renal failure, and intracranial pressure monitoring. Intracranial hypertension is treated with mannitol and/or acute short-term hyperventilation, but if the patient is refractory to treatment, mild-moderate hypothermia is achieved by a cooling blanket that is continued throughout OLT. Barbiturate coma is only used in refractory cases as the last treatment modality. Seizures are aggressively treated with phenytoin, with additional diazepam as needed. Candidacy and activation for OLT should be completed as early as possible in the course of ALF, especially in “hyperacute” cases such as acetaminophen toxicity. The final decision to proceed with OLT is made when a donor organ becomes available. King’s College Hospital criteria for OLT are still the best prognostic assessment for fatal outcome in ALF, but the criteria fail to identify some patients who will die.     

Acute pancreatitis,acute hepatitis and acute renal failure favourably resolved in two renal transplant recipients

Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function     

The Effects of Chronic Ethanol Ingestion on Ethanol Binding to Hepatic Cytochrome P-450 and on Certain Hepatic and Renal Parameters in the "Long Sleep" and "Short Sleep" Mouse

Male mice selected for genetic differences in ethanol-induced sleep time, thereby designated long sleep (LS) and short sleep (SS), were treated with the Lieber-DeCarli liquid diet for 25 days. This chronic ethanol treatment produced an increase in liver/body weight and kidney/body weight in SS mice only. In addition, chronic ethanol treatment produced significant increases in both LS and SS treated mice in in vivo ethanol elimination, hepatic cytochromes P-450 and B_s, NADPH cytochrome c reductase and hepatic and renal 7-ethoxycoumarin O-de-ethylase activity. Geno-typic differences were observed in the magnitude of response of microsomal ethanol oxidation per mg of microsomal protein (SS > LS). Further, control LS and SS mice possessed substantially different activity of renal 7-ethoxycoumarin O-de-ethylase. Both lines exhibited similar induced renal 7-ethoxycoumarin O-de-ethylase activity after chronic ethanol ingestion. Ethanol binding spectra produced when ethanol was added to hepatic microsomes were examined using double reciprocal plots. Chronic ethanol ingestion produced genotypically related (LS > SS) increases in the absorbance change maximum per mg of microsomal protein. No significant changes in the spectral dissociation constant or absorbance change maximum per nM cytochrome P-450 were observed following ethanol treatment.     

Fulminant hepatic failure from heat stroke requiring liver transplantation

A 16-year-old man developed heat stroke during football practice when the temperature was 33.8 degrees C (heat index, 44.4 degrees C). Resuscitation with ice water lavage, external cooling, and intravenous fluids was initially successful, but the patient again became obtunded. Liver chemistry tests and the prothrombin time and serum ammonia increased markedly, and rhabdomyolysis and renal failure became evident, necessitating hemodialysis. He underwent liver transplantation for fulminant hepatic failure approximately 72 hours after admission. Rhabdomyolysis with renal failure and severe electrolyte disturbances continued despite aggressive hemodialysis and the patient had a cardiopulmonary arrest and died 10 days after transplantation. This case shows that liver transplantation cannot always overcome the generalized toxic effects of heat stroke. More aggressive hemodialysis or combined liver/kidney transplantation might result in a positive outcome in selected cases.