Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation.

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC(0-12)) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC(0-12) was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Jejunal varix bleeding with extrahepatic portal vein obstruction after pylorus-preserving pancreatoduodenectomy: report of two cases.

We present 2 patients showing afferent jejunal varix bleeding around hepaticojejunostomy caused by extrahepatic portal vein obstruction after pylorus-preserving pancreatoduodenectomy (PPPD). The case 1 was a 58-year-old woman who had recurrent anemia and hematochezia 3 years after undergoing PPPD. On the portography, the main portal vein was obliterated and collaterals around hepaticojejunostomy were developed. After percutaneous transhepatic balloon dilatation and stent placement through the obliterated portal vein, jejunal varices had disappeared and thereafter no bleeding occurred for 32 months. The case 2 was a 71-year-old man who had frequent melena 7 years after PPPD. Portal stent insertion was first tried, but failed due to severe stenosis of the main portal vein. Therefore, meso-caval shunt operation was attempted in order to reduce the variceal flow. Although an episode of a small amount of melena occurred one month after the shunt operation, there was no occurrence of bleeding for the next 8 months. For the treatment of jejunal varices, a less invasive approach, such as the angiographic intervention of stent insertion, balloon dilatation, or embolization is recommended first. Surgical operations, such as a shunt or resection of the jejunal rim, could be considered when noninvasive approaches have failed.