Dong Hwan Jung

Hepatic Arterial Stenosis Assessed with Doppler US after Liver Transplantation: Frequent False-Positive Diagnoses with Tardus Parvus Waveform and Value of Adding Optimal Peak Systolic Velocity Cutoff

PURPOSE To evaluate the utility of the tardus parvus waveform of the hepatic artery at Doppler ultrasonography (US) in the diagnosis of hepatic arterial stenosis in liver transplant (LT) recipients and determine whether the accuracy of such a diagnosis is enhanced by including an optimal peak systolic velocity (PSV) cutoff. MATERIALS AND METHODS This retrospective study was institutional review board approved; the requirement for informed consent was waived. The authors identified 361 LT recipients (267 male, 94 female) who underwent Doppler US and either computed tomography (CT) or angiography, with an interval between these examinations of less than 1 week. At Doppler US, tardus parvus pattern was defined as a waveform with a resistive index (RI) of less than 0.5 and a systolic acceleration time longer than 0.08 second. At CT or angiography, patients were assigned to the hepatic arterial stenosis (≥50% vessel narrowing) or nonstenosis group. The capability of the tardus parvus pattern to facilitate the diagnosis of hepatic arterial stenosis was calculated. The difference in PSV between the true- and false-positive tardus parvus patterns was evaluated. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff PSV for diagnosing hepatic arterial stenosis. The capability of the tardus parvus pattern and an optimal PSV cutoff in the diagnosis of hepatic arterial stenosis was determined. RESULTS Sixty transplant recipients had the tardus parvus pattern at Doppler US. The sensitivity, specificity, and positive predictive value (PPV) of the tardus parvus pattern were 72% (23 of 32 LT recipients), 88.8% (292 of 329 LT recipients), and 38% (23 of 60 LT recipients), respectively. The false-positive rate was 11.2% (37 of 329 LT recipients). ROC analysis revealed an optimal PSV cutoff of less than or equal to 48 cm/sec for diagnosing hepatic arterial stenosis. The combination of the tardus parvus pattern and a PSV cutoff of less than or equal to 48 cm/sec improved specificity to 99.1% (326 of 329 LT recipients) and the PPV to 88% (22 of 25 LT recipients), thereby reducing the false-positive rate to 1% (three of 329 LT recipients) while slightly decreasing the sensitivity to 69% (22 of 32 LT recipients). CONCLUSION Use of the tardus parvus waveform of the hepatic artery resulted in a low PPV and a high false-positive rate. However, the combination of the tardus parvus pattern and an optimal PSV cutoff greatly improved the PPV and reduced the false-positive rate in the diagnosis of hepatic arterial stenosis.

Neurologic complications in adult living donor liver transplant recipients

Abstract:  Background:  Neurologic complications (NC) after liver transplantation are not uncommon, with serious complications such as central pontine myelinolysis (CPM), often causing disability.

Robotic versus laparoscopic liver resection: a comparative study from a single center.

PurposeThe significant advantages of robotic surgery have expanded the scope of surgical procedures that can be performed through minimally invasive techniques. The aim of this study was to compare the perioperative outcomes between robotic and laparoscopic liver surgeries at a single center.MethodsFrom July 2007 to October 2011, a total of 206 patients underwent laparoscopic or robotic liver surgery at the Asan Medical Center, Seoul, Korea. We compared the surgical outcomes between robotic liver surgery and laparoscopic liver surgery during the same period. Only patients who underwent left hemihepatectomy or left lateral sectionectomy were included in this study.ResultsThe robotic group consisted of 13 patients who underwent robotic liver resection including 10 left lateral sectionectomies and three left hemihepatectomies. The laparoscopic group consisted of 17 patients who underwent laparoscopic liver resection during the same period including six left lateral sectionectomies and 11 left hemihepatectomies. The groups were similar with regard to age, gender, tumor type, and tumor size. There were no significant differences in perioperative outcome such as operative time, intraoperative blood loss, postoperative liver function tests, complication rate, and hospital stay between robotic liver resection and laparoscopic liver resection. However, the medical cost was higher in the robotic group.ConclusionsRobotic liver resection is a safe and feasible option for liver resection in experienced hands. The authors suggest that since the robotic surgical system provides sophisticated advantages, the retrenchment of medical cost for the robotic system in addition to refining its liver transection tool may substantially increase its application in clinical practice in the near future.

Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients

ABO incompatibility is the most common cause of donor rejection during the initial screening of adult patients with end‐stage liver disease for living donor liver transplantation (LDLT). A paired donor exchange program was initiated to cope with this problem without ABO‐incompatible LDLT. We present our results from the first 6 years of this exchange adult LDLT program. Between July 2003 and June 2009, 1351 adult LDLT procedures, including 16 donor exchanges and 7 ABO‐incompatible LDLT procedures, were performed at our institution. Initial donor‐recipient ABO incompatibilities included 6 A to B incompatibilities, 6 B to A incompatibilities, 1 A to O incompatibility, 1 A+O (dual graft) to B incompatibility, 1 O to AB incompatibility, and 1 O to A incompatibility. Fourteen matches (87.5%) were ABO‐incompatible, but 2 (12.5%) were initially ABO‐compatible. All ABO‐incompatible donors were directly related to their recipients, but 2 compatible donors were each undirected and unrelated directed. After donor reassignment through paired exchange (n = 7) or domino pairing (n = 1), the donor‐recipient ABO status changed to A to A in 6, B to B in 6, O to O in 1, A to AB in 1, A+O to A in 1, and O to B in 1, and this made all matches ABO‐identical (n = 13) or ABO‐compatible (n = 3). Two pairs of LDLT operations were performed simultaneously on an elective basis in 12 and on an emergency basis in 4. All donors recovered uneventfully. Fifteen of the 16 recipients survived, but 1 died after 54 days. In conclusion, an exchange donor program for adult LDLT appears to be a feasible modality for overcoming donor‐recipient ABO incompatibility. Liver Transpl , 2010.

Morphometric and simulation analyses of right hepatic vein reconstruction in adult living donor liver transplantation using right lobe grafts

The incidence of clinically significant right hepatic vein (RHV) stenosis after adult living donor liver transplantation has been higher than expected. In this study, an assessment of the risk factors for the development of RHV stenosis in this context was undertaken. Hepatic anatomy, surgical techniques, and the incidence of RHV stenosis 1 year after transplantation were evaluated retrospectively in 225 recipients of right lobe grafts. These patients underwent independent RHV reconstruction, which was facilitated by the application of computed tomography morphometry and computational simulation analyses. Three types of preparation of the orifice of the graft RHV and 7 types of preparation for venoplasty of the recipient RHV were used. The frequency of high, middle, and low sites of RHV insertion into the inferior vena cava (IVC) was 56.0%, 36.4%, and 7.6%, respectively, for donors, and 26.7%, 58.7%, and 14.7%, respectively, for recipients. Nine patients (4%) developed RHV stenosis of early onset that required stent insertion during the first 2 postoperative weeks; in 12 patients (5.3%), RHV stenosis of delayed onset occurred. Inappropriate matching of RHV sites of insertion correlated with the incidence of stenosis of early onset (P = 0.039). Technical refinements to avoid adverse consequences of inappropriate ventrodorsal matching of RHV sites of insertion include making the recipient RHV orifice wide and enlarging the recipient IVC by a customized incision and patch venoplasty after anatomical assessment of the RHV and IVC of the graft and recipient. Liver Transpl 16:639‐648, 2010.

A clinical assessment of mycophenolate drug monitoring after liver transplantation

Hwang S, Lee S‐G, Ahn C‐S, Kim K‐H, Moon D‐B, Ha T‐Y, Song G‐W, Jung D‐H, Choi N‐K, Kim K‐W, Yu Y‐D, Park G‐C, Park P‐J, Choi Y‐I. A clinical assessment of mycophenolate drug monitoring after liver transplantation.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01166.x
© 2010 John Wiley & Sons A/S.

Results of a phase 4 trial of Tacrobell® in liver transplantation patients: A multicenter study in South Korea

BACKGROUND/AIMS This 26-week pilot study was performed in de novo liver transplant recipients to evaluate the efficacy of tacrobell capsule as an immunosuppressant drug after living donor liver transplant patients by determining the rate of acute cellular rejection after its use and evaluating its safety after transplantation. METHODOLOGY From October 2005 to July 2007, 57 patients from four major medical centers in Seoul, South Korea were enrolled in the study. This open-label, noncomparative, multicenter pilot study lasted 26 weeks and assigned patients to receive tacrobell and corticosteroid after liver transplantation. Tacrobell (0.05mg/ kg/day, bid) and methylprednisolone were injected either on the day of the operation or on postoperative day one. A retrospective matched control group consisting of living donor liver transplant recipients at one center (Asan medical center) was used for comparison. RESULTS The rate of acute cellular rejection with Tacrobell after 26 weeks of administration was 0.0% (95% CI, 0.0%-6.27%), which was below our hypothesized 36%. The most common drug-related adverse events included endocrine/nutritional disorders followed by gastrointestinal and hepatobiliary disorders. No patients died during the study period. The side effect profile of this drug was no different than other tacrolimus based immunosuppressants. CONCLUSIONS Although our study was based on a low risk population and had a shortterm follow up, we conclude that tacrobell, as a generic tacrolimus, can be considered safe and effective in liver transplant patients.

Intensive Pulmonary Support Using Extracorporeal Membrane Oxygenation in Adult Patients Undergoing Liver Transplantation

BACKGROUND/AIMS Adult liver transplantation (LT) recipients occasionally show serious acute cardiopulmonary dysfunction, requiring intensive care. We have assessed the feasibility of extracorporeal membrane oxygenation (ECMO) support in adult LT recipients facing acute pulmonary failure and refractory to conventional mechanical ventilation and concurrent nitric oxide gas inhalation. METHODOLOGY From January 2008 to June 2009, 9 adult LT recipients required ECMO support due to pneumonia (n=5) and adult respiratory distress syndrome (n=4). Mean age was 52.6 ± 5.9 years and mean model for end-stage liver disease score was 29.0 ± 7.5. Five patients underwent living-donor LT and four underwent deceased-donor LT. RESULTS Veno-venous access mode was used and continuous veno-venous hemodiafiltration was performed concurrently in all 9 patients. No procedure related complications occurred. Successful ECMO weaning was achieved in 4 patients (44.4%) at the first attempt, after mean ECMO support of 12.0 ± 6.8 days but the other five died due to overwhelming infection prior to ECMO weaning. Univariate analysis revealed no significant risk factors for failing ECMO support before ECMO start. CONCLUSIONS ECMO as rescue therapy seems beneficial to be considered as a final therapeutic option for LT recipients with refractory pulmonary dysfunction who would otherwise die due to hypoxemia.

Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

Abstract Acute liver failure (ALF) is a severe life‐threatening disease which usually arises in patients with‐irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase‐1, E‐NTPDase1 (CD39) and ecto‐5′‐nucleotidase, Ecto5′NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)‐1&agr;, and improve ischemic tolerance to ALF. To test our hypothesis, liver biopsies were obtained and we found that CD39 and CD73 mRNA and proteins from human specimens were dramatically elevated in ALF. We investigated that induction of CD39 and CD73 in ALF‐related with wild type mice. In contrast, deletion of cd39 and cd73 mice has severe ALF. In this study, we concluded that CD39 and CD73 are molecular targets for the development of drugs for ALF patients care. Graphical abstract Figure. No Caption available. HighlightsHIF‐1a is stabilized during acute liver failureUpregulation of CD39 and CD73 following acute liver failureCD39 and CD73 are transcriptionally induced by HIF‐1aDeletion of Cd39 and CD73 aggravates murine acute liver failureDMOG treatment induces HIF‐1a stabilization, CD39 and CD73 during acute liver failure in WT mice

Preoperative peripheral blood human telomerase reverse transcriptase mRNA concentration is not a prognostic factor for resection of hepatocellular carcinoma.

BACKGROUND/AIMS Hepatocellular carcinoma (HCC) often recurs after complete surgical resection. Detection of markers of residual circulating cancer cells may predict postoperative HCC recurrence. Human telomerase reverse transcriptase (hTERT) mRNA may be a candidate tumor marker. METHODOLOGY We prospectively assessed the expression patterns and prognostic value of preoperative peripheral blood hTERT mRNA in patients with HCC undergoing hepatic resection (n=17) or liver transplantation (n=6). As controls, we assessed hTERT mRNA in patients with liver cirrhosis without HCC (n=6) and in living liver donors (n=4). Concentrations of hTERT mRNA were measured by real-time quantitative reverse transcription polymerase chain reaction (RTPCR). RESULTS No significant difference was observed in the levels of hTERT mRNA between the HCC and control groups. Only alpha-fetoprotein ≥400ng/mL was associated with greater expression levels of hTERT mRNA. At a median follow-up of 30 months, HCC recurred in 10 of 17 resected patients, but in none of the 6 liver transplant recipients. hTERT mRNA concentration was not associated with HCC recurrence after either resection or liver transplantation. CONCLUSIONS Peripheral blood hTERT mRNA concentration is not a likely marker for the diagnosis or prognosis of HCC, especially in patients undergoing resection. Owing to the small number of transplanted patients assessed, the clinical significance of hTERT mRNA concentration was not objectively verified, suggesting the need for a study in larger numbers of HCC patients undergoing liver transplantation.