T. Yoshizumi

Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma

Sarcopenia was identified recently as a poor prognostic factor in patients with cancer. The present study investigated the effect of sarcopenia on short‐ and long‐term outcomes following partial hepatectomy for hepatocellular carcinoma (HCC), and aimed to identify prognostic factors.

Feasibility of left lobe living donor liver transplantation between adults: An 8-year, single-center experience of 107 cases

Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5–1%. To minimize the risk to the donor, left lobe (LL)‐LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL‐LDLT between adults based on a single‐center experience of 107 LL‐LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1‐, 3‐ and 5‐year patient survival rates in LL‐LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL‐LDLT. Twenty‐six grafts (24.3%) were lost for various reasons with three losses directly attributable to small‐for‐size graft syndrome. Post‐operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL‐LDLT was found to be a feasible option in adult‐to‐adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.

Left Lobe Living Donor Liver Transplantation in Adults

Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short‐ and long‐term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1‐, 5‐ and 10‐year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small‐for‐size syndrome was higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT.

Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity

Mitochondria contribute to cellular innate immunity against RNA viruses. Mitochondrial-mediated innate immunity is regulated by signalling molecules that are recruited to the mitochondrial membrane, and depends on the mitochondrial inner membrane potential (Δψm). Here we examine the physiological relevance of Δψm and the mitochondrial-associating influenza A viral protein PB1-F2 in innate immunity. When expressed in host cells, PB1-F2 completely translocates into the mitochondrial inner membrane space via Tom40 channels, and its accumulation accelerates mitochondrial fragmentation due to reduced Δψm. By contrast, PB1-F2 variants lacking a C-terminal polypeptide, which is frequently found in low pathogenic subtypes, do not affect mitochondrial function. PB1-F2-mediated attenuation of Δψm suppresses the RIG-I signalling pathway and activation of NLRP3 inflammasomes. PB1-F2 translocation into mitochondria strongly correlates with impaired cellular innate immunity, making this translocation event a potential therapeutic target.

Primary Graft Dysfunction After Living Donor Liver Transplantation Is Characterized by Delayed Functional Hyperbilirubinemia

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult‐to‐adult LDLT grafts without anatomical, immunological or hepatitis‐related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH‐20) was used to characterize PGD. DFH‐20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH‐20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT‐INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH‐20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH‐20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.

Living Donor Liver Transplantation Using Dual Grafts from Two Donors: A Feasible Option to Overcome Small-for-Size Graft Problems?

Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small‐for‐size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large‐size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small‐for‐size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small‐for‐size graft problems without increasing independent donor risks.

Revisiting the Safety of Living Liver Donors by Reassessing 441 Donor Hepatectomies: Is a Larger Hepatectomy Complication‐Prone?

Donor safety is of paramount importance in performing living donor liver transplantation (LDLT). We retrospectively reviewed donor medical records to confirm whether larger donor hepatectomy is absolutely complication‐prone. A total of 441 living donor hepatectomies were performed between October 1996 and July 2012 in our institute, which were divided into three eras (Era I, October 1996 to March 2004; Era II, April 2004 to March 2008; Era III, April 2008 to July 2012) and the incidences of postoperative complications were compared among the three types of hepatectomy—right hepatectomy (RH), left hepatectomy (LH) and left lateral segmentectomy (LLS). Although severe complications (Claviens grade 3 or more) frequently occurred in RH in Eras I and II (15.4% and 10.7%, respectively), the incidence in Era III decreased to the comparable level observed in LH and LLS (5.4% in RH, 2.3% in LH and 5.3% in LLS). The incidence of postoperative complications did not relate to the type of hepatectomy selected in the latest era. Since most complications after hepatectomy were considered preventable, step‐by‐step meticulous surgical procedures are a prerequisite for further assuring donor safety irrespective of the type of hepatectomy selected.

The Benefits of Interferon Treatment in Patients Without Sustained Viral Response After Living Donor Liver Transplantation for Hepatitis C

UNLABELLED Although it has been recognized that interferon (IFN) treatment is crucial for recurrent hepatitis C after liver transplantation, its benefits have not been determined among patients without a sustained viral response (SVR). METHODS Eighty patients who received IFN plus ribavirin treatment after living donor liver transplantation were grouped as follows: group I (n = 18) SVR; group II (n = 25) no-SVR but viral response [VR] positive; Group III (n = 13) no-VR but biochemical response [BR] positive; and group IV (n = 24) no-VR and no-BR. RESULTS In groups II and III, not only the histological activity grade and fibrosis stage, but also the serum parameters including transaminases and type IV collagen were stable for 3 years after induction of IFN-based treatment. In group I, the activity grade and fibrosis stage significantly improved (P < .01). In group IV, the fibrosis stage significantly deteriorated (P < .01); the serum transaminases and type IV collagen were significantly higher than the other groups (P < .01). The mean duration of IFN treatment was significantly longer among group II (96 weeks) compared with the other cohorts (P < .05). The 5-year graft survival rate in groups II (91%) and III (100%) were comparable to those of group I (100%); group IV (62%) was significantly lower than the other groups (P < .05). CONCLUSION IFN treatment was beneficial even among subjects with IFN-dependent VR or BR, although they did not achieve SVR.

Donor Age in Living Donor Liver Transplantation

BACKGROUND We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. METHODS Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age < or =50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age < or =50, n = 61). We compared post-LDLT graft functions. RESULTS Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. CONCLUSION Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT.

Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension.

The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients.