Significance of monitoring plasma concentration of voriconazole in a patient with liver failure: A case report.

RATIONALE: Invasive pulmonary aspergillosis is associated with significant morbidity and mortality in patients with liver failure. Voriconazole (VRCZ) is recommended as a primary therapeutic agent for the treatment of invasive aspergillosis and metabolized in the liver. Now, data are still lacking on the safety and appropriate dosage of VRCZ in patients with liver failure. Here, we report a representative case of invasive pulmonary fungal infection in a patient with liver failure who was treated with low-dose VRCZ. PATIENT CONCERNS: A 21-year-old man, presented with subacute liver failure caused suspected by viral infection, was admitted on June 22, 2014. Liver function was not improved by the treatment of gancicolovir and methylprednisolone. The patient presented with fever, cough, and hyperpyrexia on July 14. Laboratory tests revealed raised neutrophil percentage (82.1%, normal range [NR] 50-70), international normalized ratio (INR) (2.32, NR 0.8-1.2) and levels of serum lactic acid (4.308 mmol/L, NR 0.6-2.2), alanine transaminase (165 U/L,NR 0-40), aspartate transaminase (99 U/L, NR 8-40), and total bilirubin (654 mmol/L, NR 3.4-20.5). Furthermore, CD4+ T cell, CD8+T cell, and B cell count were low (169, 221, and l8/mL, respectively). Sputum smear microscopy for bacteria was negative, but the direct observation for fungal elements was positive. Thoracic CT scan revealed bilateral pulmonary high-density shadow. Sputum cultures were positive 2 days later with the presence of Aspergillus fumigatus. DIAGNOSES: Therefore, this patient diagnosed with suspected pulmonary a spergillosis. INTERVENTIONS: VRCZ was used on July 15th and its dosage was 400 mg twice on day 1 followed by a maintenance dose of 100 mg twice daily according to drug usage instruction. However, some side effects, such as tremors, lips twitching, and hair loss, occurred. Plasma VRCZ trough concentration was 8.1 mg/mL which was much higher than the recommend level. Therefore, VRCZ dosage was adjusted according to its plasma concentration. VRCZ plasma concentration fluctuated between 2.5 to 4.7 mg/mL when its dosage was 100 mg once daily and side effects disappeared. OUTCOMES: VRCZ was administered for 2 months. This patient's symptoms and liver function were improved. A follow-up CT scan performed at the end of VRCZ therapy indicated that the high-density shadow had diminished. LESSONS: This case demonstrated that low-dose VRCZ (maintenance dose, 100 mg/day) can achieve effective plasma concentration and reduce side effects without liver damage. We believe that VRCZ is safe to be administered in patients with liver failure, but its plasma concentration should be carefully monitored.

Schistosoma mansoni infection in the liver graft: The impact on donor and recipient outcomes after transplantation.

The increasing number of transplants performed each year has led to the identification of unusual diseases in liver grafts from asymptomatic donors that were unrecognized before liver transplantation. Here we report our experience with patients who received liver grafts infected with schistosomiasis. From September 1991 to August 2010, 482 pediatric liver transplants were performed at A. C. Camargo Hospital/Sírio-Libanês Hospital (São Paulo, Brazil). For the identification of Schistosoma mansoni infections, pathology slides for the recipients were reviewed; these included postreperfusion and follow-up liver biopsy samples. We were able to identify 6 cases of schistosomiasis transmitted through infected grafts (5 of these grafts were from living donors). All living donors were confirmed to have normal liver chemistries, negative fecal tests for parasitic diseases, and normal abdominal ultrasound findings. Liver biopsy was not performed before transplantation. In all cases, features of schistosomiasis were absent in the liver explants. The living donors were treated with praziquantel and were taught to avoid risk factors for reinfection. No specific treatment for schistosomiasis was given to the recipients. There were no perioperative deaths, but 2 recipients died after living donor liver transplantation (LDLT) because of Kaposi's sarcoma and non-Hodgkin's lymphoma. In conclusion, using liver grafts infected with S. mansoni eggs did not compromise the results of LDLT in this pediatric cohort. Because of the parasite's life cycle and the therapeutic target of praziquantel, only donors should be treated for the infection. Three years of follow-up showed an uneventful recovery for the living donors.

Acute renal failure in Plasmodium malariae infection.

We report an unusual case of transfusion-transmitted malaria which remained undiagnosed for several months in an Italian woman splenectomised and polytransfused for thalassaemia major. The infecting species was Plasmodium malariae, and the patient developed acute renal failure, severe thrombocytopenia, and hepatic failure. Treatment with chlorochine was followed by a slow, but complete recovery of renal function.

Second case of neurocysticercosis in a patient with liver transplantation (first case in Spain): a case report.

BACKGROUND: Neurocysticercosis (NCC) is a disorder caused by the Taenia solium larva. It is the most common parasitosis of the central nervous system (CNS). Its distribution is universal, but it is endemic in many developing countries and in the third world. In Spain most patients come from countries where the condition is endemic. However, sporadic cases occur among the population of rural regions. NCC in transplant recipients is uncommon. One renal transplant recipient developed NCC but responded to treatment with praziquantel. Recently, it has been reported to complicate a liver transplantation. CASE REPORT: The patient was a 49-year-old Ecuatorian man who received a cadaveric donor liver graft in June 2001 due to acute liver failure induced by toadstool and was under treatment with FK506. In January 2006, the patient presented with a generalized onset of a tonic-clonic seizure for 1 minute without sphincter incontinence, headache, fever, or previous brain trauma. Neurological evaluation did not show evidence of organic brain dysfunction. The neuroimaging findings (brain) computed tomography scan, magnetic resonance imaging were compatible with NCC: many cystic lesions intra- and extraparenchymatous with a scolex visible in three of them. Serology for cysticercosis in plasma was initially indeterminate but positive afterward. The patient was treated with anticonvulsivants (valproic acid) and albendazole. Systemic steroids were added in order to reduce the edema produced upon death of the cyst. Treatment lasted 3 weeks and it was completed without complications or neurological symptoms. Liver function was not affected. One year later the patient remained asymptomatic. CONCLUSION: NCC is a condition that must be included in the differential diagnosis of patients with CNS involvement and cystic lesions on neuroimaging investigations in transplant recipients, especially patients originating from or traveling to endemic areas. First-line therapy for active cysts includes antiparasitic drugs (albendazole or praziquantel) as well as steroids and anticonvulsivants. In our patient, this therapy was effective.

Plasmodium falciparum and hepatitis E virus co-infection in fulminant hepatic failure.

Acute hepatitis E and falciparum malaria can each present with fulminant hepatic failure and are common in tropical countries. However, co-existence of these two conditions has not been reported. We report a 20-year-old girl who presented with fever and altered sensorium. Peripheral smear was positive for Plasmodium falciparum, and IgM anti-HEV was positive. She died despite antimalarial drugs and supportive management. Postmortem liver tissue showed changes suggestive of acute viral hepatitis.

[Schistosoma mansoni schistosomiasis]. / Schistosomose à Schistosoma mansoni.

Schistosomosis are parasitic diseases caused by blood flukes of the Schistosoma genus. The pathology of schistosomosis is mostly brought about by ova trapped in the tissues. In the liver, granuloma around ova eventually trigger periportal fibrosis and portal hypertension. In S. mansoni infection, the infection intensity and the onset of liver fibrosis are under distinct genetic control. Liver fibrosis is the main cause of death in the 20 millions individuals suffering from chronic schistosomosis. However, liver fibrosis is reversible if antischistosomal drugs are administered before the onset of severe hepatic insufficiency.

The coagulation profile in hepatosplenic schistosomiasis.

The biological activity of blood coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen and prekallikrein was assessed in 15 healthy subjects and 60 patients with endemic Egyptian hepatosplenomegaly. The degree of liver disease was graded according to the Child-Pugh classification, the intensity of S. mansoni infection was monitored by determination of circulating schistosome immune complexes (CSIC) level using a monoclonal antibody and hemostasis activation was detected by measurement of hemostatic markers D-dimer and prothrombin fragment 1 + 2 (F1+2). Functional activity of antithrombin III, alpha2-antiplasmin and protein C as well as quantitative determination of plasma concentrations of alpha1-antitrypsin, C1 activator inhibitor and alpha2-macroglobulin were also carried out. The progressive deterioration of liver function which matched the severity of the disease and the intensity of schistosomal infection led to a reduction in anticoagulant proteins (decreases in antithrombin III and protein C) resulting in hypercoagulability and thrombin generation (increased F1+2) subsequently followed by consumption (prolongation of coagulation screening tests, thrombocytopenia, hypofibrinogenemia and decreased factor VIII resulting in hypocoagulability and secondary fibrinolysis (increased D-dimer and decreased alpha2-antiplasmin). A significant decline in fibrinogen and factors VII, XII and prekallikrein was detected in bleeders compared with ascitic patients. The decline in factor XII was closely related to CSIC high titers in all disease groups, but was not correlated to D-dimer or F1+2 concentrations. This suggests that circulating schistosome immune complexes may exert an inhibitory effect on contact factor XII which should be taken into account when considering the reasons for schistosomal coagulopathy and bleeding in hepatosplenic schistosomiasis.