Damage to mtDNA in liver injury of patients with extrahepatic cholestasis: the protective effects of mitochondrial transcription factor A.

Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of chronic liver cholestasis. Mitochondrial DNA (mtDNA) is highly susceptible to oxidative stress and mtDNA damage leads to mitochondrial dysfunction. This study aimed to investigate the mtDNA alterations that occurred during liver injury in patients with extrahepatic cholestasis. Along with an increase in malondialdehyde (MDA) levels and a decrease in ATP levels, extrahepatic cholestatic patients presented a significant increase in mitochondrial 8-hydroxydeoxyguanosine (8-OHdG) levels and decreases in mtDNA copy number, mtDNA transcript levels, and mtDNA nucleoid structure. In L02 cells, glycochenodeoxycholic acid (GCDCA) induced similar damage to the mtDNA and mitochondria. In line with the mtDNA alterations, the mRNA and protein levels of mitochondrial transcription factor A (TFAM) were significantly decreased both in cholestatic patients and in GCDCA-treated L02 cells. Moreover, overexpression of TFAM could efficiently attenuate the mtDNA damage induced by GCDCA in L02 cells. However, without its C-tail, ΔC-TFAM appeared less effective against the hepatotoxicity of GCDCA than the wild-type TFAM. Overall, our study demonstrates that mtDNA damage is involved in liver damage in extrahepatic cholestatic patients. The mtDNA damage is attributable to the loss of TFAM. TFAM has mtDNA-protective effects against the hepatotoxicity of bile acid during cholestasis.

Operative timing of liver transplantation for patients with severe hepatitis.

BACKGROUND: Fulminant hepatic failure manifests a rapid onset, serious complications, and a high mortality, but still there is a possibility of recovery. Once the patient is able to pass a crisis, the liver is able to regenerate completely and regain its normal function. Therefore it is of vital importance to determine the eligible timing for transplantation. Premature surgery might result in a loss of the chance of internal medical treatment and misuse of liver resources, whereas delayed surgery might increase the difficulty of treatment in the preoperative period and the possibility of complications and medical expense, which eventually result in decreased rate of success and survival. This problem remains worldwide how to choose the optional timing of operation. METHODS: Thirty-six patients with severe hepatitis were treated by orthotopic liver transplantation. The distribution of MELD scores in these patients was: 10-19 in 8 patients, 20-29 in 10, 30-39 in 11, and 40 in 7. They were divided into two groups: MELD score <30 and MELD score >or=30. Parameters (1-year survival rate, complications, preoperative use of artificial liver, operative time, volume of bleeding and blood transfusion, and average hospital costs) were examined as prognostic factors after liver transplantation. RESULTS: The 1-year survival rate of the MELD score <30 group was higher than that of the >or=30 group (77.8% and 33.3%, P=0.007), and the rate of complications in the <30 group was lower (P=0.012). There were no differences in the timing of artificial liver treatment, operative time, operative hemorrhage, and transfusion between the two groups (P=0.742). But the average daily hospital cost in the MELD score >or=30 group was higher (P=0.008). CONCLUSION: This study shows that when the MELD score is <30 it may be the optimal time to perform liver transplantation for patients with severe hepatitis.

[Hand-assisted laparoscopic hepatectomy for large liver cancer in 56 cases].

OBJECTIVE: To investigate the practical value of hand-assisted laparoscopic hepatectomy for large liver cancer in peripheral segments. METHODS: From March 2004 to December 2007, 56 patients with large liver cancer underwent hand-assisted laparoscopic hepatectomy including 53 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma, 1 case of hepatic metastatic squamous carcinoma. RESULTS: The operation procedures were completed safely in all patients including 27 left lateral segment hepatectomy, 6 left hemi-hepatectomy and 23 atypical right hepatectomy. Thirty-one cases with hepatic hilum blocking in the procedure and the mean time was 16.7 minutes. Mean surgical time was 105.3 minutes. Mean blood loss was 97 ml. Mean gross tumor size was 8.6 cm. Mean excisional hepatic tissue volume was 10.5 cm. No serious postoperative complications occurred. Mean eating time was 2.1 days. The mean postoperative hospital stay was 7.3 days. CONCLUSION: Hand-assisted laparoscopic hepatectomy for large liver carcinoma is feasible and safe for selected patients.

Liver transplant for 70 patients with end-stage liver diseases.

BACKGROUND: Liver transplantation has evolved as a successful treatment for patients with end-stage liver cirrhosis and acute liver failure. Postoperative survival rates have increased to 90% in 1 year and 80% in 5 years as a result of improvements in immunosuppression, perioperative management and surgical techniques. However, a wide range of postoperative complications are of technical or medical origin. This study was undertaken to determine the relationship between the technical improvements and optimal timing of surgery and its outcome. METHODS: From April 1999 to October 2005, typical orthotopic or piggyback liver transplantation was performed in 70 patients (58 men and 12 women, aged 19-74 years). Twenty-four patients had liver carcinoma and cirrhosis, and 46 had benign liver disease. RESULTS: All patients survived the operation and 14 died in the first month after surgery because of respiratory failure (6), respiratory failure accompanied by acute renal failure (4), intra-abdominal hemorrhage and infection (2), and cerebral edema (2). A total of 76 complications occurred in the 70 patients after operation: pneumonia (34), right pleural effusion (11), bile leakage (7), postoperative intra-abdominal hemorrhage and infection (4), acute renal failure (4), acute rejection (3), wound infection (2), biliary tract stenosis (2), severe cholangitis derived from cholelith (2), morphological alteration of biliary tree (2), cerebral edema (2), empyema (1), chronic rejection (1), and wound hematoma (1). Finally, 33 patients survived more than 6 months, 16 more than 1 year, 4 more than 2 years, and 2 more than 6 years after operation. The perioperative survival rate was 80% in this series. CONCLUSIONS: Liver transplantation is an effective treatment for patients with end-stage liver disease. To obtain good results, improvements of surgical technique, optimal timing and better postoperative care are needed.