A 39-yr-old male patient was admitted to our liver intensive care unit (LICU) for acute liver failure on August 20, 2009. The patient worked at a leather-manufacturing plant, where he cleaned animal coats by using PCE. The patient informed us that he occasionally did not wear protective devices during this procedure and that the process room at the plant was poorly ventilated. After working for about 50 days, the patient suddenly began passing dark urine, but continued his regular work. During the next 4 days, the patient developed progressive jaundice with nausea, vomiting, loss of appetite, and weakness and was admitted to a local hospital. Blood chemistry revealed the following findings: total bilirubin (TBIL), 202.8 microM/L (normal range, 3.0-20.0 microM/L); alanine aminotransferase (ALT), 743 U/L (normal range, 5-40 U/L); alkaline phosphatase (ALP), 189 U/L (normal range, 15-130 U/L); and gamma glutamyl transferase (GGT), 99 U/L (normal range, 12-58 U/L). Serum concentration of PCE was 2.8 mg/L and urinary concentration of trichloroacetic acid (TCA)-an indirect biomarker for PCE poisoning-was 8.4 mg/L. Treatment with hepatoprotective agents failed to achieve any remission. Further, the patient developed coagulopathy associated with progressive deterioration of liver function, which in turn led to the development of grade II hepatic encephalopathy within 48 hr. Therefore, he was transferred to our hospital.
The patient had no notable exposure to toxic chemicals before this job. He denied smoking or alcohol or drug use before the onset of the symptoms. The patient had not received blood transfusion; not traveled recently; had no family history of liver disease; and none of his colleagues had similar manifestations. On the day of admission to the LICU, all his vital signs were within normal limits. Physical examination revealed grade II hepatic encephalopathy with confusion, slurred speech, asterixis, and disorientation for time and place. The patient had severe jaundice, but without peripheral edema. The patient developed ecchymoses at the therapeutic puncture sites. The liver, spleen, and kidneys were not palpable. Abdominal or costovertebral angle tenderness was not detected.
Laboratory examinations performed at the time of admission showed the following biochemical results: ALT, 1,100 U/L; aspartate aminotransferase (AST), 355 U/L (normal range, 10-40 U/L); TBIL, 421.8 microM/L; direct serum bilirubin (DBIL), 197.3 microM/L (normal range, 0.0-7.0 microM/L); ALP, 201 U/L; GGT, 139 U/L; prothrombin time (PT) 51.0 s (normal range, 9.0-12.8 s); international normalized ratio (INR), 3.32 (normal range, 0.8-1.4); ammonia, 151 microM/L (normal range, 9-33 microM/L); alfa-fetoprotein (AFP), 1,045 ng/mL (normal range, 0-9 ng/mL); and normal electrolyte, hematological, and renal functions. Peripheral T-lymphocyte subpopulations, analyzed by flow cytometry, showed CD4/CD8 ratio of 3.74 (normal range, 1.33-1.99). Serological studies for viral hepatitis (hepatitis A, B, C, D, and E viruses; human immunodeficiency virus; Epstein-Barr virus; cytomegalovirus) and autoimmunity markers (antinuclear, antimitochondrial, antineutrophil cytoplasmic, anti-smooth-muscle, and anti-liver-kidney microsome antibodies) were negative. Screening studies were performed to detect genetic and metabolic liver diseases and hematochromatosis, Wilson's disease, and alpha 1-antitrypsin deficiency were excluded. Doppler ultrasonography of the patient's abdomen revealed homogeneous echogenic liver that had decreased in size; had patent portal veins, hepatic artery, and hepatic veins; and no obstruction of the biliary tracts. The spleen appeared normal, and no ascites was observed.
The patient was managed with general supportive care along with intravenous administration of dexamethasone (15 mg daily) for 5 consecutive days. He was also treated with liver-protective preparations, glutathione, ademetionine, hepatocyte growth-promoting factors, and prophylactic antibiotics. Furthermore, plasmapheresis was performed on days 1, 3, and 5, with 3,000 mL of plasma exchanged during each session. Gradually, the patient's mental status became normal, and liver function, coagulation profiles and other biochemical variables improved notably (Fig. 1). The maximum AFP level was 3,000 ng/mL. The patient underwent percutaneous liver biopsy on day 12; the biopsy revealed massive hepatocellular necrosis prominently in the centrilobular area with moderate inflammatory infiltration mainly of lymphocytes and neutrophils. We also detected diffuse swelling of the hepatocytes and hemorrhagic infiltration in some necrotic areas. Neither obvious expansion of portal vein nor increased deposition of fibrous tissue was detected. Bile ducts appeared normal except for cholangioles with bile plugs (Fig. 2). The pathological features indicated drug-induced acute liver injury. The patient responded well to treatment, and gradually, his general condition improved and all symptoms eventually resolved except for poor appetite and fatigue. The patient was discharged from the hospital on day 26 and advised to completely avoid exposure to PCE at his workplace.
The patient underwent regular follow-up every month, and liver function and AFP level became normal after 2 months. Repeat liver biopsy performed 6 months after discharge showed fibrous expansion of the portal tracts caused by moderate inflammatory infiltration and nodular regeneration of the hepatic parenchyma delimited by thin fibrous bands and septa. The biopsy showed evidence of some swollen hepatocytes and scattered foci of hepatocellular necrosis within the liver lobules (Fig. 3). Currently, the patient is undergoing anti-liver fibrosis therapy using modern Chinese medicine (Fuzhenghuayu capsule) and continues to receive follow-up.