Right hepatic venous system variation in living donors: a three-dimensional CT analysis.

BACKGROUND: The right hepatic venous system consists of the right hepatic vein (RHV) and inferior RHVs (IRHVs). When the right posterior section is used as a graft for liver transplantation, understanding variations and relationships between the RHV and IRHVs is critical for graft venous return and hepatic vein reconstruction. This study aimed to evaluate variations in the hepatic veins and the relationships between them. METHODS: The medical records and CT images of patients who underwent hepatectomy as liver donors were assessed retrospectively. The relationship between the veins was evaluated by three-dimensional CT. RESULTS: The configuration of the posterior section was classified into one of eight types based on the RHV and IRHVs in 307 patients. Type 1a (103 of 307), type 1b (139 of 307) and type 2a (40 of 307) accounted for 91·9 per cent of the total. The diameter of the RHV extending towards the inferior vena cava had a significant inverse correlation with that of the IRHV (r2  = -0·615, P < 0·001). Type 1a, which had no IRHVs, had the RHV with the largest diameter; conversely, type 2a, which had a large IRHV, had the RHV with the smallest diameter. CONCLUSION: The hepatic venous system of the right posterior section was classified into eight types, with an inverse relationship between RHV and IRHV sizes. This information is useful for segment VII resection or when the right liver is used as a transplant graft.

ANTECEDENTES: El sistema venoso hepático derecho consiste en la vena hepática derecha (right hepatic vein, RHV) y las RHVs inferiores (IRHVs). Cuando se utiliza la sección posterior derecha hepática como injerto para el trasplante hepático, es fundamental conocer las variaciones e interrelaciones entre la RHV y las IRHVs para el retorno venoso del injerto y la reconstrucción de la vena hepática. El objetivo de este estudio fue determinar las variaciones en las venas hepáticas y sus interrelaciones. MÉTODOS: Se evaluaron retrospectivamente las historias clínicas y las imágenes de la tomografía computarizada de los pacientes que se sometieron a una hepatectomía como donantes vivos para trasplante hepático. La interrelación entre las venas se evaluó mediante imágenes de CT tridimensional. RESULTADOS: La configuración de la sección posterior clasificó a 307 pacientes en base a la RHV y a las IRHVs. Se clasificaron en 8 tipos, de los cuales el Tipo 1a (103/307), el Tipo 1b (139/307) y el Tipo 2a (40/307) representaron el 92% del total. El diámetro de la RHV que se extiende hacia la vena cava inferior presentó una correlación inversa significativa con la de las IRHV (r2: −0,632, P < 0,0001). El diámetro mayor de la RHV se observó en el Tipo 1a, que no presentaba IRHVs; por el contrario, el diámetro más pequeño se observó en el Tipo 2a que presentaba una IRHV grande. CONCLUSIÓN: El sistema venoso hepático de la sección posterior derecha se clasificó en 8 subtipos con una relación inversa entre los tamaños de la RHV y las IRHV. Esta información es útil cuando se practica una resección del segmento 7 o cuando se utiliza el hígado derecho como injerto para el trasplante.

Fatty change in moderately and poorly differentiated hepatocellular carcinoma on MRI: a possible mechanism related to decreased arterial flow.

AIM: To clarify the frequency of fatty change in moderately and poorly differentiated hepatocellular carcinomas (mHCCs and pHCCs) and its relationship to arterial blood flow. MATERIALS AND METHODS: One hundred and thirty-six surgically resected HCC lesions were studied. All patients had undergone dynamic magnetic resonance imaging (MRI) with chemical-shift-encoded water-fat imaging (CSI). The presence of fat was identified by a signal drop-off on CSI and confirmed at pathology. Lesions were classified into four groups in the arterial phase; G1, hypointense; G2, isointense; G3, slightly and heterogeneously hyperintense; G4, markedly and homogeneously hyperintense. The number of cumulative arteries (CAs) in the tumours in the pathology examination were counted. RESULTS: A fat component was observed significantly more frequently in the pHCCs (13/21; 61.9%) compared to the mHCCs (32/101; 31.7%; p=0.013). The numbers of lesions in each group were as follows: (G1, G2, G3, G4) = (18, 9, 23, 4) in the HCCs with fat; (1, 6, 24, 51) in the HCCs without fat (p<0.001); (5, 5, 18, 4) in the mHCCs with fat; (0, 3, 19, 47) in the mHCCs without fat (p<0.001); (11, 0, 2, 0) in the pHCCs with fat; (0, 2, 3, 3) in the pHCCs without fat (p=0.001). The number of CAs in the fat-containing HCCs (5.5±2.9) was significantly lower than that in the HCCs without fat (10.8±5.3; p<0.001). CONCLUSION: A fat component was more commonly observed in the pHCCs than in the mHCCs. The present results showed a possible mechanism of fatty change in mHCCs and pHCCs in relation to decreased arterial blood supply.

Correlation between portal vein anatomy and bile duct variation in 407 living liver donors.

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.

Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living-donor liver transplantation.

BACKGROUND: A precise estimation of the capacity of the remnant liver following partial liver resection is important. In this study, the regional function of the liver in patients undergoing living-donor liver transplantation was evaluated by gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (EOB)-enhanced MRI, with special reference to the congested region. METHODS: EOB-MRI analysis was performed before hepatectomy in donors, and 7 days after surgery in the donor and recipient. In the hepatocyte phase, from images obtained 15 min after Primovist® injection, the signal intensity in each liver segment was measured and divided by the signal intensity of the erector spinae muscle (liver to muscle ratio, LMR) for standardization. Inter-regional differences in LMRs were analysed in donors and recipients. RESULTS: Thirty-two living donors and 31 recipients undergoing living-donor liver transplantation were enrolled. In donors, the LMRs of the remnant left lobe were almost equivalent among the liver segments. In the remnant right lobe without the middle hepatic vein, the mean(s.d.) LMR for congested segments (S5 and S8) was significantly lower than that for non-congested segments (S6 and S7): 2·60(0·52) versus 3·64(0·56) respectively (P < 0·001). After surgery, values in the non-congested region were almost identical to those in the preoperative donor liver. LMR values in the left and right lobe graft were significantly lower than those in the corresponding segment before donor surgery (P < 0·001). CONCLUSION: The function of the congested region secondary to outflow obstruction in the remnant donor liver was approximately 70 per cent of that in the non-congested region. EOB-MRI is a promising tool to assess regional liver function, with good spatial resolution.

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 (Clavien's 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.

Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant.

The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN)α and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R(2) = 0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk ΔG allele (P = 0.003 and P = 0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P = 0.4). In recipients with the risk ΔG allele, IFNL4 ΔG mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 ΔG expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation.

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

BACKGROUND: 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. METHODS: Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7-10 days after laparoscopic splenectomy were analysed. RESULTS: Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P < 0·050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P < 0·001). Portal vascular resistance was also reduced, by 21 per cent (P = 0·009). The peripheral blood concentration of ET-1 decreased from 2·95 to 2·11 pg/ml (P < 0·001), and that of NOx tended to decrease (from 29·2 to 25·0 pg/ml; P = 0·068). In hepatic venous blood, the level of ET-1 decreased from 2·37 to 1·83 pg/ml (P = 0·006), whereas NOx concentration tended to increase (from 24·5 to 30·9 pg/ml; P = 0·067). CONCLUSION: In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed.

Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

BACKGROUND: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). METHODS: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. RESULTS: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. CONCLUSIONS: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

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

BACKGROUND: 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. METHODS: Data were collected retrospectively for all consecutive patients who underwent hepatectomy for HCC with curative intent between January 2004 and December 2009. Patients were assigned to one of two groups according to the presence or absence of sarcopenia, assessed by computed tomographic measurement of muscle mass at the level of the third lumbar vertebra. Clinicopathological, surgical outcome and long-term survival data were analysed. RESULTS: Sarcopenia was present in 75 (40·3 per cent) of 186 patients, and was significantly correlated with female sex, lower body mass index and liver dysfunction, as indicated by abnormal serum albumin levels and indocyanine green retention test at 15 min values. In patients with, and without sarcopenia, the 5-year overall survival rate was 71 and 83·7 per cent respectively, and the 5-year recurrence-free survival rate was 13 and 33·2 per cent respectively. Multivariable analysis revealed that reduced skeletal muscle mass was predictive of an unfavourable prognosis. CONCLUSION: Sarcopenia was predictive of worse overall survival even when adjusted for other known predictors in patients with HCC after partial hepatectomy.

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.

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.

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.

The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation: significant lessons from a dual graft case.

IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.

C-reactive protein : albumin ratio in patients with resectable intrahepatic cholangiocarcinoma.

BACKGROUND: The C-reactive protein : albumin ratio (CAR) has been reported as a novel prognostic marker in several cancers. The aim of this study was to investigate the prognostic value of CAR in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: This was a single-centre retrospective study of patients who underwent surgery for ICC in a university hospital in Japan between 1998 and 2018. CAR, Glasgow Prognostic Score (GPS) and modified GPS (mGPS) were calculated. Their correlation with recurrence-free survival (RFS) and overall survival (OS) was analysed with Cox proportional hazards models. RESULTS: Seventy-two patients were included in the study. Patients were divided into two groups according to the optimal CAR cut-off value of 0·02. CAR above 0·02 was associated with higher carbohydrate antigen 19-9 levels (20·5 versus 66·1 units/ml for CAR of 0·02 or less; P = 0·002), larger tumour size (3·2 versus 4·4 cm respectively; P = 0·031) and a higher rate of microvascular invasion (9 of 28 versus 25 of 44; P = 0·041). RFS and OS were shorter in patients with CAR above 0·02: hazard ratio (HR) 4·31 (95 per cent c.i. 2·02 to 10·63) and HR 4·80 (1·85 to 16·40) respectively. In multivariable analysis CAR above 0·02 was an independent prognostic factor of RFS (HR 3·29 (1·33 to 8·12); P < 0·001), but not OS. CONCLUSIONS: CAR was associated with prognosis in patients who had hepatic resection for ICC.

ANTECEDENTES: La relación proteína C reactiva/albumina (C-reactive protein/albumin ratio, CAR) ha sido descrita como un marcador pronóstico novedoso en varios tipos de cáncer. El objetivo de este estudio fue investigar el valor pronóstico de CAR en pacientes con colangiocarcinoma intrahepático (intrahepatic cholangiocarcinoma, ICC). MÉTODOS: Se trata de un estudio retrospectivo y unicéntrico de pacientes sometidos a cirugía por ICC en un hospital universitario de Japón entre 1998 y 2018. Se calcularon CAR, puntuación pronóstica de Glasgow (Glasgow prognostic score, GPS), y GPS modificada (mGPS). Se analizó su correlación con la supervivencia libre de recidiva (recurrence-free survival, RFS) y con la supervivencia global (overall survival, OS) mediante modelos de riesgos proporcionales de Cox. RESULTADOS: Se incluyeron un total de 72 pacientes. El valor de corte óptimo de CAR fue de 0,02. Los pacientes se dividieron en dos grupos de acuerdo a este valor de corte. La presencia de CAR > 0,02 se asoció con niveles más elevados de antígeno carbohidrato 19-9 (20,5 U/ml versus 66,1 U/ml; P = 0,002), mayor tamaño tumoral (3,2 cm versus 4,4 cm; P = 0,031) y una tasa más elevada de invasión microvascular (32,1% versus 56,8%; P = 0,041). La RFS y OS fueron más cortas en pacientes con CAR > 0,02 (cociente de riesgos instantáneos, hazard ratio, HR 4,305; i.c. del 95% 2,016-10,63 y HR 4,803; i.c. del 95% 1,846-16,40, respectivamente). En los análisis multivariables, CAR de > 0,02 fue un factor pronóstico independiente para RFS (HR 3,286; i.c. del 95% 1,330-8,118; P < 0,001), pero no para la OS. CONCLUSIÓN: CAR se asoció con el pronóstico en pacientes sometidos a resección hepática por ICC.

[Noonan syndrome with atrial septal defect and hypertrophic cardiomyopathy].

Noonan syndrome is one of the most common nonchromosomal syndromes seen in children with congenital heart disease. The major cause of death is congestive heart failure. We report a case of Noonan syndrome with hypertrophic cardiomyopathy and arterial septal defect (ASD). Since 10 years old he had been suffering from congestive heart failure. ASD patch closure with a fenestrated flap valve patch was performed at 12 years of age. After operation, left-to-right shunt flow through the patch gradually decreased and he was discharged at 19 postoperative day in good condition.

[Ventricular septal defect with aortic valvular regurgitation complicated with infective endocarditis; report of a case].

We report a case of ventricular septal defect (VSD) associated with infective endocarditis complication of aortic and pulmonary valvular regurgitation. He received treatment for pyelonephritis and after 2 months he was suffering from congestive heart failure. Echocardiography showed vegetation on the aortic valve and the anterior semilunar cusp of the pulmonary valve. He was referred to our department for surgical repair. Aortic valvular replacement, pulmonary valvular repair and direct closure of VSD were performed. The postoperative course was uneventful and the patient discharged at 28 postoperative day.