Kazutoyo Morita

Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C

Background and aims: MicroRNAs are small non‐coding RNA molecules that post‐transcriptionally regulate gene expression. Liver‐specific microRNA‐122 (miR‐122) has been shown to facilitate the replication of hepatitis C virus (HCV) in human hepatoma cells in vitro. However, the clinical significance of hepatic miR‐122 on HCV in human body is unclear.

Living Donor Hepatectomies with Procedures to Prevent Biliary Complications

BACKGROUND Biliary complications in donor hepatectomies are still common, and occur in approximately 5% of the procedures. STUDY DESIGN To evaluate the usefulness of the management and surgical procedures to prevent the biliary complications in donor hepatectomies, a total of 343 donors were retrospectively studied. The clinical and surgical parameters of the donors and the postoperative biliary complications were evaluated. RESULTS Fourteen donors had biliary complication (BC) during the follow-up period (4.1%). Donors were divided into 2 groups; donors without BC (non-BC group; n = 329) and donors with BC (BC group; n = 14). Mean peak level of total bilirubin, mean duration of hospital stay after surgery, and medical cost in the BC group were significantly higher than in the non-BC group (p < 0.01). As improved procedures to prevent the BC were established at 2005, including the use of a real-time cholangiography by the C-arm, a minimized dissection of the hepatic vessels, the meticulous closure of the bile duct, and/or the use of Pringle maneuver during the parenchymal transection, the donors were divided into 2 groups before and after these establishments (the early period, n = 173; the later period, n = 170). Refinements in the management and surgical procedures reduced the occurrence of biliary complications from 6.4% during the early period to 1.8% during the later period (p < 0.01), and no biliary complications in the last 69 consecutive donors were observed. CONCLUSIONS Technical refinements described in this study might be useful to prevent the occurrence of biliary complications in a donor hepatectomy. It is particularly important to preserve the blood supply for the biliary tract of both the graft and the remnant liver.

A simple hilar dissection technique preserving maximum blood supply to the bile duct in living donor liver transplantation.

Duct-to-duct reconstruction is associated with a higher incidence in biliary strictures in living donor liver transplantation (LDLT). However, a standard dissection technique for the recipients bile duct has not been established. Here, we describe a simple bile duct dissection technique preserving maximum vascular integrity during total hepatectomy of the recipient. The present technique might facilitate duct-to-duct bile duct reconstruction in both right and left lobe LDLT and, thus, contribute to reduce biliary complications such as biliary strictures. We believe that this technique can be a standard in the field of LDLT.

Comparative evaluation of expanded criteria for patients with hepatocellular carcinoma beyond the Milan criteria undergoing living-related donor liver transplantation.

Shirabe K, Taketomi A, Morita K, Soejima Y, Uchiyama H, Kayashima H, Ninomiya M, Toshima T, Maehara Y. Comparative evaluation of expanded criteria for patients with hepatocellular carcinoma beyond the Milan criteria undergoing living‐related donor liver transplantation.
Clin Transplant 2011: 25: E491–E498.

Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation

Background. We introduced a new technique called minimal hilar dissection (Min-HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipients bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. Methods. An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. Results. There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min-HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1- and 3-year, respectively. The median period for treating BAS was 10.8 months. Conclusion. The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT.

Congestion of the donor remnant right liver after extended left lobe donation.

The clinical importance of congestion of the remnant right lobe has not yet been fully elucidated in donors who donate their left lobe with the middle hepatic vein. The impact of congestion on clinical course and liver regeneration in 52 donor remnant livers were evaluated. The donors were divided into three groups according to the degree of the congestion: the mild [congestion ratio (CR) < 10%], moderate (CR ranged from 10% to 25%) and severe congestion groups (CR > 25%). The regeneration ratio of the graft at postoperative day 7 (7 POD) was 22.0 ± 14.3% and inversely correlated with the CR in the remnant right lobe (P = 0.003). Aspartate aminotransferase and alanine aminotransferase at 7 POD were significantly higher in the severe CR group in comparison to the mild CR group (P = 0.003 and 0.019, respectively), but those of the three groups were comparable at 30 POD. The hospital stays were significantly longer in the severe CR group (P = 0.010). In conclusion, the congestion of the donors’ remnant right liver can lead the transient liver dysfunction and poor regeneration. Therefore, the conversion of the graft from the left to right lobe might be appropriate according to the degree of the congestion.

Predictors of microscopic portal vein invasion by hepatocellular carcinoma: Measurement of portal perfusion defect area ratio

Objective:  Microscopic portal vein invasion (PVI) by cancer cells is a poor prognostic factor after hepatic resection for hepatocellular carcinoma (HCC). The aim of this study is to predict PVI preoperatively in patients with HCC.

Impact of Human T Cell Leukemia Virus Type 1 in Living Donor Liver Transplantation

Human T cell leukemia virus type 1 (HTLV‐1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV‐1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV‐1 status in living donor liver transplantation (LDLT). Twenty‐six of 329 (7.9%) HTLV‐1 carriers underwent primary LDLT. One recipient negative for HTLV‐1 before LDLT received a graft from an HTLV‐1 positive donor. Eight donors were HTLV‐1 positive. Twenty‐seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV‐1 positive donors and two from negative donors. The 1‐, 3‐ and 5‐year HTLV‐1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV‐1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development.

De Novo Hepatocellular Carcinoma in a Liver Graft with Sustained Hepatitis C Virus Clearance After Living Donor Liver Transplantation

The occurrence of de novo hepatocellular carcinoma (HCC) after liver transplantation (LT) for advanced HCCs has been extremely limited. In this article, a case of de novo HCC in a liver graft with sustained hepatitis C virus clearance after living donor liver transplantation (LDLT) for multiple HCCs and hepatitis C cirrhosis is reported. The recipient was a 58‐year‐old female, and the left lobe living donor was the 30‐year‐old healthy daughter of the recipient. Three years after LDLT, the patient received 48 weeks of interferon treatment for recurrent hepatitis C with advanced fibrosis. The patient has shown successful viral clearance since then. However, an HCC was recognized in the liver graft during a follow‐up computed tomography scan performed 6 years after LDLT, and it was surgically resected. To analyze its origin [either from the patient (metastatic) or from the living donor (de novo)], genotyping by microsatellite analysis of tissue and blood samples from the donor and recipient was performed, and it revealed that the HCC originated from the donor. To the best of our knowledge, this is the first report of de novo HCC in a liver graft with sustained hepatitis C virus clearance after LT for advanced HCCs and hepatitis C cirrhosis. Liver Transpl 15:1412–1416, 2009.

Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation.

The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short‐term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram‐negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post‐LDLT pneumonia was associated with the following post‐LDLT events: the prolonged use of mechanical ventilation (≥3 days), a prolonged stay in the intensive care unit (≥7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed‐onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad‐spectrum antibiotics and aminoglycosides provided cover for most gram‐negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad‐spectrum antibiotics. Delayed‐onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed. Liver Transpl, 2012.