Successful Treatment of Fibrosing Cholestatic Hepatitis With Daclatasvir and Asunaprevir After Liver Transplantation: A Case Report.

BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after liver transplantation (LT). Most FCH cases are fatal, occurring as a secondary disease following rapidly progressive liver dysfunction and graft failure. We report a case of early-onset FCH after LT that was successfully treated using daclatasvir and asunaprevir. CASE REPORT: A 59-year-old woman underwent living donor LT for HCV-related liver cirrhosis. However, liver function was not improved after LT and gradually worsened. A liver biopsy was performed at 30 and 47 days after the living donor LT to identify the cause of the liver dysfunction. The first biopsy result showed no specific finding. However, combined treatment with pegylated interferon and ribavirin was started because of a high HCV viral load (> 8.0 log IU/mL). Nevertheless, liver function and HCV viral load deteriorated, and the second biopsy performed on postoperative day 47 revealed FCH. We converted the antiviral agents into daclatasvir and asunaprevir and performed plasmapheresis twice. Since then, the liver dysfunction and HCV viral load gradually improved, and HCV RNA clearance occurred at week 11 after treatment. The patient achieved a sustained virologic response at week 24 after completion of the treatment. CONCLUSION: Daclatasvir combined with asunaprevir can be a useful treatment option in potentially fatal FCH after LT.

Urgent Living-Donor Liver Transplantation in a Patient With Concurrent Active Tuberculosis: A Case Report.

BACKGROUND: Although active tuberculosis (TB) is considered a contraindication for liver transplantation (LT), this is the only treatment in patients with liver failure and concurrent active TB. We report a case with successful urgent living-donor LT for irreversible liver failure in the presence of active TB. CASE PRESENTATION: A 48-year-old man, with a history of decompensated alcoholic liver cirrhosis, was presented with stupor. At admission, his consciousness had deteriorated to semi-coma, and his renal function also rapidly deteriorated to hepatorenal syndrome. A preoperative computed tomography scan of the chest revealed several small cavitary lesions in both upper lobes, and acid-fast bacillus stain from his sputum was graded 2+. Adenosine deaminase levels from ascites were elevated, suggesting TB peritonitis. A first-line anti-TB drug regimen was started immediately (rifampin, isoniazid, levofloxacin, and amikacin). An urgent living-donor LT was performed 2 days later. After LT, the regimen was changed to second-line anti-TB drugs (amikacin, levofloxacin, cycloserine, and pyridoxine). The sputum acid-fast bacillus stain tested negative on postoperative day 10. His liver function remained well preserved, even after the reversion to first-line anti-TB treatment. The patient recovered without any anti-TB medication-related complications and was discharged. CONCLUSIONS: LT can be prudently performed as a life-saving option, particularly for patients with liver failure and concurrent active TB.

Veno-Arterial-Venous Hybrid Mode of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome Combined With Septic Shock in a Liver Transplant Patient: A Case Report.

BACKGROUND: Post-operative respiratory failure is common in liver transplant patients, with a direct effect on graft and recipient outcomes. We present a case of successful treatment for a patient who had acute respiratory distress syndrome combined with septic shock after living-donor liver transplantation with veno-arterial-venous hybrid mode of extracorporeal membrane oxygenation (ECMO) support. METHODS: A 49-year-old male patient underwent successful emergency living-donor liver transplantation for acute-on-chronic liver failure associated with alcoholic liver cirrhosis. The patient was diagnosed with concurrent active pulmonary tuberculosis and tuberculosis peritonitis just before emergency liver transplantation. Intermittent post-operative small-bowel obstruction caused by adhesions from tuberculosis peritonitis was nonresponsive to conservative management. RESULTS: On post-operative day 114, we performed emergency adhesio-lysis because of bowel ischemia signs. However, the patient had progressive deterioration of arterial oxygenation despite conventional ventilatory support and nitric oxide gas inhalation, and septic shock resulted from aspiration pneumonia. Therefore, we decided to administer ECMO. After initiation of ECMO support, hemodynamic status, pneumonic consolidation, and oxygenation status gradually improved, and the patient was weaned from ECMO on the 11th day. Finally, the patient was discharged on post-transplant day 204. CONCLUSIONS: ECMO can be a beneficial rescue option for the management of refractory cardiopulmonary failure in liver transplant recipients. In addition, the hybrid mode of ECMO is a helpful salvage option when conventional modes of ECMO are inadequate.

Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice.

The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high-performance liquid chromatography. The plasma and tissue NADPH oxidase and matrix metalloproteinases (MMP)-9 activities were analyzed by fluorescence spectrophotometry. The cumulative disease index and disease peaks were significantly higher in HFD-EAE compared with those in ND-EAE. Significantly higher 5-HT levels and lower 5-HT turnovers 5-hydroxyindole acetic acid ((5-HIAA)/5-HT) were found in the brains of HFD-EAE mice compared with those found in the HFD-CON and ND-EAE mice brains. Moreover, increased DA levels were observed in the caudate nucleus of the HFD-EAE mice compared with the control and ND-EAE mice. The NADPH oxidase and MMP-9 activities in the plasma and tissues were significantly higher in both the ND-EAE and HFD-EAE groups than in their respective controls. The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice.

Updated status of deceased-donor liver graft allocation for high-urgency adult patients in a Korean high-volume liver transplantation center.

BACKGROUND: The number of deceased organ donors in Korea has been gradually increased to reach 8 per million population. This study intended to analyze the updated status of urgent deceased-donor liver transplantation in a Korean high-volume liver transplantation center. METHODS: A retrospective study was performed with a 4-year study period from 2010 to 2013. RESULTS: During the study period, 328 adult patients were enrolled at the Asan Medical Center for urgent orthotopic liver transplantation (OLT) with Korean Network for Organ Sharing status 1 in 56 (17.1%) and status 2A in 272 (82.9%). Of them, 201 (61.3%) were allocated for OLT and 195 (58.2%) actually underwent OLT after exclusion of 6 cases of spontaneous withdrawal. In KONOS status 1, liver grafts were initially allocated to 33 (58.9%), but 6 were withdrawn owing to clinical improvement, so 27 (48.2%) actually underwent OLT. In status 2A, 168 (61.8%) underwent OLT within 2 weeks of priority waiting period. According to ABO blood groups in recipients, the allocation probability was 68% (68 of 100) in group A, 60.6% (60 of 99) in group B, 64.1% (25 of 39) in group AB, and 53.3% (48 of 90) in group O. Mean waiting period for OLT was 5.7 ± 2.1 days. CONCLUSIONS: Deceased donor incidence of ∼8 per million population contributed to meeting ∼60% of the demand for urgent deceased-donor liver transplantation in a Korean transplantation center, so further increasing deceased organ donor numbers is necessary to improve the current status of organ shortage.

Liver transplantation in Korea: past, present, and future.

PURPOSE: This study reviewed the past and present status of liver transplantation (LT) and outlooks for the future of LT in Korea. METHOD: The first LT in Korea was successfully performed using a deceased donor graft in 1988. Pediatric and adult living donor liver transplantations (LDLTs) were initiated in 1994 and 1997, respectively. From 1988 to 2013, 10,581 LTs were performed at 40 centers, whereas LDLT accounted for 76.5% of all LTs. RESULTS: In the early 1990s, the deceased organ donation rate was less than 1.5 per million population (PMP) per year, but it increased to 5 PMP beginning in 2008. Despite the increasing number of deceased donor liver transplantations (DDLTs), high prevalence of hepatitis B virus (HBV)-induced cirrhosis and hepatocellular carcinoma (HCC) has provoked persistent performance of adult LDLT with technical advancement including middle hepatic vein (MHV) reconstruction of right lobe graft and dual graft LDLT with 1 nationwide donor mortality. CONCLUSION: The number of LTs in Korea in 2010 was 23.2 PMP (1042 LTs/45 million population), lower than 23.5 PMP of Spain, but higher than 20 PMP of the United States. However, future LT numbers may decrease because of lowering the HBV carrier rate (neonatal HBV universal vaccination began in 1992), new potent anti-HBV agents, and lowest birth rate (1.22 children per family) with a decrease of potential live donors.

Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin.

BACKGROUND AND AIMS: Despite the application of prophylaxis, the risk of hepatitis B virus (HBV) recurrence remains. However, actual mechanism(s) and definite risk factor(s) are obscure. The present study examined the correlation between the HBV load in liver explants and post-liver transplant (OLT) HBV recurrence. METHODS: HBV DNA was extracted from liver tissue taken from 50 living donor OLT (LDLT) patients using the QuickGene DNA Tissue Kit S (Fujifilm, Tokyo, Japan) and subjected to real-time polymerase chain reaction with the following primers: 5'-CACATGGCCTCCAAGGAGTAA-3' (forward primer) and 5'-TGAGGGTCTCTCTCTTCCTCTTGT-3' (reverse primer). To prevent HBV infection, patients were treated daily with high-dose (10,000 IU) hepatitis B immunoglobulin (HBIG) for the first week after LDLT. They then received weekly doses for the next month and then monthly doses for ≤1 year. If the anti-hepatitis surface antigen antibody titer was <1,000 IU/L, an antiviral agent (AVA) was added to the regimen. RESULTS: The mean (±SD) tissue HBV DNA and covalently closed circular DNA (cccDNA) loads were -0.8 ± 1.2 (range, -2.9 to 2.6) and -2.3 ± 1.1 (range, -4.6 to 0.6) log10 copies/cell, respectively. There was a significant correlation between serum and tissue HBV DNA (r = 0.65; P = .00) and cccDNA concentrations (r = 0.55; P = .00). Six patients suffered HBV recurrence and 9 required additional AVA. There was no direct correlation between HBV recurrence and tissue cccDNA concentration. However, the concentration of cccDNA was significantly greater those patients suffering recurrence and receiving AVA treatment (high-risk group). CONCLUSION: High tissue cccDNA concentrations may be a risk factor for HBV recurrence despite high-dose HBIG prophylaxis.

External biliary drainage in living donor liver transplantation using duct-to-duct anastomosis.

PURPOSE: This study compared the incidence of biliary complication (BC) in adult living donor liver transplant recipients who underwent right-lobe duct-to-duct anastomosis (DDA) with or without external biliary drainage (EBD) and intended to optimize EBD tube clamping. METHODS: This study consisted of a retrospective assessment of EBD effect and a prospective trial for EBD tube-clamping optimization. The retrospective study included the EBD group (n = 208) and the non-EBD group (n = 145). The prospective study included 60 patients with EBD. RESULTS: In the retrospective study, single DDA was performed in 83.7% of the EBD group and 80.7% of the non-EBD group (P = .47). One-year overall incidence of BC was 14.4% in the EBD group and 16.8% in the non-EBD group (P = .48). The incidence of early anastomotic bile leakage was 1.0% in the EBD group and 4.8% in the non-EBD group (P = .036). In the prospective study, there was no difference in tube-clamping success rates between low- and high-output EBD groups. There was also no statistical difference between the success and failure groups in terms of graft duct size, liver function tests, and post-transplant days at tube clamping. CONCLUSIONS: The size of our EBD tube was too small for the graft duct size, therefore its main role appeared to be early biliary decompression, which helped prevent bile leakage and also simplified the route of cholangiogram in detecting early BC. Hence, EBD is worthy of performing in selected patients with a high risk of anastomotic bile leak.

Long-term outcome of living donor liver transplantation for patients with alcoholic liver disease.

BACKGROUND: Because most liver transplantation (LT) studies for alcoholic liver disease (ALD) were performed on deceased donor LT, little was still known following living donor LT (LDLT). METHODS: The clinical outcomes of 126 ALD patients who underwent LDLT for 11 years in a high-volume LT center were assessed retrospectively. RESULTS: ALD cases were 5.7% of adult LDLT indication (n = 2196). ALD was 1.9% (4 of 207) during 2000 to 2001, whereas the proportion gradually increased up to 11.3% (34 of 301) in 2010. The model for end-stage liver disease score was 22.1 ± 9.9, and 6-month abstinence was observed in 105 (83.3%). There were 123 (97.6%) related donors. Single-graft and dual-graft were implanted into 111 and 15 patients, respectively. Main graft type was single right liver graft (n = 108; 85.7%). Graft-to-recipient weight ratio was 1.02 ± 0.16. Perioperative mortality within 3 months occurred in 5 (4.0%). Overall 1-, 3-, 5-, and 10-year patient survival rates were 92.1%, 88.0%, 85.8%, and 83.7%, respectively. Three patients died of alcohol abuse. De novo hepatitis B virus infection occurred in 2 of 26 patients after implantation of core antibody-positive graft and no further cases happened after strict application of prophylaxis. CONCLUSIONS: The results of this study revealed that the survival outcome of LDLT in ALD patients is comparable with that of deceased donor LT. To achieve favorable long-term survival, a multidisciplinary approach can be an effective strategy, including the interaction between the patient, the physician, and the family members.

Long-term survival analysis of liver transplantation for hepatocellular carcinoma with bile duct tumor thrombus.

BACKGROUND: Long-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT. METHODS: A retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases. RESULTS: Types of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (P = .019). CONCLUSIONS: The results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.

Complications analysis of polytetrafluoroethylene grafts used for middle hepatic vein reconstruction in living-donor liver transplantation.

BACKGROUND: We previously showed that ringed polytetrafluoroethylene (PTFE) grafts combined with small allograft patches showed high patency rates similar to those of iliac vein grafts and therefore that they can be used for middle hepatic vein (MHV) reconstruction. Although such use of PTFE graft showed high patency rates, its long-term safety regarding infection and other types of complications were not presented. In this study, we investigated the actual risk of complications directly associated with PTFE graft interposition for MHV reconstruction. METHODS: During the study period of 30 months, we performed 215 cases of adult living-donor liver transplantation with modified right lobe graft and PTFE grafts. We classified the potential complications directly associated with PTFE graft interposition as infectious and surgical complications. The medical records of study patients were retrospectively reviewed. RESULTS: MHV graft patency rate was 76.3% at 6 months and 36.7% at 12 months. Their 1-year graft and patient survival rates were 92.6% and 93.5%, respectively. The 1-year actual incidences of infectious complication and surgical complication were near zero and 1 case (0.5%), respectively. In 1 recipient, the PTFE graft penetrated into the stomach wall 6 months after transplantation, but the patient did not complain of any specific symptoms. The PTFE graft was removed with the use of laparotomy, and the patient recovered uneventfully. CONCLUSIONS: Although the incidence of PTFE graft-associated complication rate is very low, we suggest that it is necessary to closely monitor the PTFE graft, because unexpected complications can happen during long-term follow-up.

Role of hand-assisted laparoscopic surgery in living-donor right liver harvest.

OBJECTIVE: The cosmetic aspects of abdominal skin incisions are a matter of concern for both live liver donors and surgeons. We performed a prospective comparative study on the use of minilaparotomy to perform right liver graft harvests with and without hand-assisted laparoscopic surgery (HALS). METHODS: Young donors were indicated for surgery using minilaparotomy with or without HALS. In the non-HALS group (n = 20), a 10-12-cm-long right subcostal incision was used for right liver graft harvest. In the HALS group (n = 20), an 8-cm-sized right subcostal incision was used for hand assistance and 3 laparoscopic holes made for manipulation. The retrohepatic inferior vena cava (IVC) was initially laparoscopically dissected while using air inflation. The skin incision was extended to 10-12 cm, and then hilar dissection and hepatic transection were performed through the skin incision. RESULTS: In all 40 donors in the study cohort, safe uneventful harvesting of the right liver grafts was successfully achieved through the minilaparotomy incisions. The HALS group required an additional 30 minutes for laparoscopic preparation and dissection compared with the non-HALS group. HALS facilitated retrohepatic IVC dissection, and the remaining part of the surgery was the same as that for minimal-incision surgery. The minimal skin incision for the delivery of the liver from the abdomen was an average 10 cm for grafts <500 g and 12 cm for grafts ≥700 g. Compared with the patient profiles, there were no differences regarding donor age, body mass index, graft weight, intraoperative blood loss, postoperative increase in peak liver enzymes, total hospital stay, and incidence of postoperative complications. CONCLUSIONS: HALS facilitates the performance of donor hepatectomy with the use of a minimal incision, which probably allows for a wider selection of living donors.

Survival rates among patients awaiting deceased donor liver transplants at a single high-volume Korean center.

BACKGROUND: Since the establishment of the Korean Network for Organ Sharing (KONOS) in 2000, thousands of patients have been enrolled on the waiting list, but only a small proportion have received a deceased donor liver transplantation. This report on waiting list mortality in Korea based on data from a single institution. METHODS: The 1772 patients enrolled on the waiting list between February 2000 and December 2011 either have not yet received at the time of analysis or have died before receiving an organ. Survival information was obtained in February 2012 by reviewing medical records or by telephone. We excluded patients who died immediately after enrollment or after retransplantation. RESULTS: Primary diagnoses of those awaiting transplantation were hepatitis B virus-associated cirrhosis (63.7%), alcoholic liver disease (14.3%), hepatitis C virus-associated cirrhosis (13.8%), and acute liver failure due to other causes (8.1%). The priority status of patients on the waiting list was KONOS status 1 (highest priority) in 3.8%, status 2A in 3.9%, status 2B in 41.9%, status 3 to 7 (lowest priority) in 50.5%. Their median survival periods were 1, 1, 18, and 59 months, respectively. The mean Child-Pugh score was 8.5 ± 2.5 and Model for End-stage Liver Disease (MELD) score 18.1 ± 9.8. CONCLUSIONS: Patients with high MELD scores or hepatocellular carcinoma succumbed soon after being entered on to the waiting list. By increasing organ donation rates and developing a risk-based allocation system, it should be possible to reduce mortality among patients on organ waiting lists.

Unification venoplasty to cope with recipient portal vein anomaly during living donor liver transplantation.

PURPOSE: To cope with recipient portal vein (PV) anomalies, such as early branching of the right posterior section (RPS), during living donor liver transplantation (LDLT) surgery, we performed a simulation study to standardize the surgical technique for unification portal venoplasty. METHODS: This study included an observational analysis of conventional methods utilizing RPS PV, simulation-based design of a new surgical technique, and clinical application of this new technique. RESULTS: In a case encountering RPS PV, a mild anastomotic PV stenosis was persistent over 6 months postsurgery, indicating the need for technical refinement. After computational simulation analysis, we found that simple suturing of the PV branch patch automatically resulted in a funnel-shaped elongation. A prospective recipient study (n = 30) indicated that usual PV reconstruction via the PV bifurcation method is feasible in the absence of unusual donor or recipient PV anomaly. Retrospective living donor PV anatomy analysis (n = 20) revealed that 20-mm-long limbs of the first-order PV branches are necessary to make a 10- to l5-mm-long funneled PV stump. This technique of unification venoplasty for an anomalous recipient PV was applied to an adult patient undergoing LDLT with a right liver graft, for which it was shown to be technically feasible and effective. CONCLUSIONS: A simplified unification venoplasty technique was developed to cope with a recipient PV anomaly in adult LDLT.

Long-term survival outcomes for living donor liver transplant recipients with pathologically nonviable hepatocellular carcinoma.

PURPOSE: Complete necrosis of hepatocellular carcinoma (HCC) lesions has occasionally been found by explant pathology after pretransplant neoadjuvant treatment. This study sought to investigate the long-term prognostic effect of loss of tumor viability after HCC treatment in living donor liver transplant (LDLT) recipients. METHODS: We reviewed retrospectively the 5-year records of 37 patients who demonstrated nonviable HCC on explant pathology. RESULTS: The most common primary disease was hepatitis-B-virus-associated liver cirrhosis (n = 34). Single explant tumors were found in 29 patients; the mean maximal tumor size was 2.1 ± 0.9 cm (range: 0.8-4.0). No patients showed microvascular invasion. The median level of alpha-fetoprotein was 12 ng/mL (range: 1-1160). The 1 patient who showed a recurrence at 20 months remains alive more than 6 years after adrenalectomy and repeated pulmonary metastasectomy. The 5-year HCC recurrence rate was thus 2.1%. There were 2 late mortalities, each due to graft failure and recurrent gastric cancer. The overall patient survival rate was 97.3% at 5 and 92.7% at 10 years. CONCLUSIONS: The results of this study revealed that the loss of tumor viability induced by pretransplant neoadjuvant treatment definitely decreased the risk of post-transplant HCC recurrence. Therefore, patients with nonviable HCC can be regarded as members of a superselect group with minimal risk for HCC recurrence, and may be exempted from routine HCC screening.

A pilot study on the safety and efficacy of generic mycophenolate agent as conversion maintenance therapy in stable liver transplant recipients.

PURPOSE: The patent covering mycophenolate mofetil (MMF) in Korea has expired and, thus, several generic MMF agents are now commercially available. The supply of Cellcept (Roche Korea) was interrupted at the end of 2011, so it was inevitable that a generic MMF would be used instead. During this period, we performed a prospective pilot study to examine the safety and efficacy of a generic mycophenolate agent (Myconol: Hanmi Pharmaceutical, Seoul Korea) for use as conversion maintenance therapy in stable liver transplantation (OLT) recipients. METHODS: OLT recipients, who were treated with MMF on an outpatient basis from January 2012 to March 2012, attended follow-up interviews conducted. The patients had undergone OLT ≥ 2 years before the study, had tolerated Cellcept, and showed stable liver function. Fifty-three patients were followed up for more than 3 months after conversion to the same dose of Myconol. RESULTS: After conversion to Myconol, 6 patients (11.3%) experienced new side effects, which disappeared when they reverted to Cellcept (n = 5) or stopped taking Myconol medication (n = 1). The side effects associated with Myconol included gastrointestinal symptoms (indigestion and diarrhea; n = 3), skin eruptions (n = 1), pruritus (n = 1), and insomnia (n = 1). The mean mycophenolic acid levels were 1.71 ± 0.88 µg/mL for Cellcept and 1.83 ± 0.91 µg/mL for Myconol, which showed a strong correlation (r(2) = 0.92, P < .001). CONCLUSIONS: Myconol showed similar pharmacokinetics to those of Celcept, but a small proportion of patients experienced agent-specific side effects; therefore, patients should be closely monitored when taking Myconol. Also, further studies, with a greater number of patients, are required to identify the full spectrum of drug-associated side effects.

Long-term outcome of liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma.

PURPOSE: Combined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC. METHODS: Between January 1999 and December 2009, we performed 2137 adult OLT at our institution including 15 cases of pathologically confirmed HCC-CCC, who all underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients. RESULTS: Their mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% at 3 and 5 years. CONCLUSIONS: Patients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.

Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

BACKGROUND: A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. METHODS: Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. RESULTS: Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. CONCLUSIONS: This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory.

Post-transplant assessment of consciousness in acute-on-chronic liver failure patients undergoing liver transplantation using bispectral index monitoring.

PURPOSE: Deterioration of consciousness is a critical situation for liver transplantation (OLT) recipients. The bispectral (BIS) index based on electroencephalographic parameters, is primarily used to monitor the depth of unconsciousness. The present study sought to assess the usefulness of posttransplant BIS index to monitor acute-on-chronic liver failure patients. METHODS: This 1-year retrospective study of 28 adult patients with acute-on-chronic liver failure was performed from July 2011 to June 2012, using post-transplant BIS monitoring. RESULTS: The mean patient age was 51 ± 8 years. Their mean pretransplant Child-Turcotte-Pugh score was 12.3 ± 1.4, and the mean Model for End-stage Liver Disease score, 36.4 ± 5.9. After OLT, the mean initial Glasgow Coma Scale (GCS) score and BIS index were 3.4 ± 1.7 and 43.5 ± 9.1, respectively. After 6 hours the mean GCS and BIS values rose to 8.6 ± 4.0 and 52.4 ± 10.3 and after 12 hours to 9.7 ± 3.4 and 61.3 ± 15.7 respectively. Eye opening in response to a voice occurred at a mean of 8.9 ± 6.7 hours after arrival in the intensive care unit regardless of graft function. The mean GCS and BIS values were 10.6 ± 2.8 and 69.1 ± 13.5, respectively. The endotracheal tube was removed after a median of 140 hours; 9 patients required a tracheostomy. Among them 2 died within the first 3 months after OLT. CONCLUSIONS: BIS monitoring is a noninvasive, simple, easy-to-interpret method to measure consciousness among patients intubated with an endotracheal tube.

Carbon nanotube mode-locked optically-pumped semiconductor disk laser.

An optically pumped semiconductor disk laser was mode-locked for the first time by employing a single-walled carbon nanotube saturable absorber. Stable passive fundamental mode-locking was obtained at a repetition rate of 613 MHz with a pulse length of 1.23 ps. The mode-locked semiconductor disk laser in a compact geometry delivered a maximum average output power of 136 mW at 1074 nm.