Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.

We previously produced mice with human hepatocyte (h-hep) chimeric livers by transplanting h-heps into albumin enhancer/promoter-driven urokinase-type plasminogen activator-transgenic severe combined immunodeficient (SCID) mice with liver disease. The chimeric livers were constructed with h-heps, mouse hepatocytes, and mouse hepatic sinusoidal cells (m-HSCs). Here, we investigated the morphological features of the chimeric livers and the h-hep gene expression profiles in the xenogeneic animal body. To do so, we performed immunohistochemistry, morphometric analyses, and electron microscopic observations on chimeric mouse livers, and used microarray analyses to compare gene expression patterns in hepatocytes derived from chimeric mouse hepatocytes (c-heps) and h-heps. Morphometric analysis revealed that the ratio of hepatocytes to m-HSCs in the chimeric mouse livers were twofold higher than those in the SCID mouse livers, corresponding to twin-cell plates in the chimeric mouse liver. The h-heps in the chimeric mouse did not show hypoxia even in the twin-cell plate structure, probably because of low oxygen consumption by the h-heps relative to the mouse hepatocytes (m-heps). Immunohistochemical and electron microscopic examinations revealed that the sinusoids in the chimeric mouse livers were normally constructed with h-heps and m-HSCs. However, a number of microvilli projected into the intercellular clefts on the lateral aspects of the hepatocytes, features typical of a growth phase. Microarray profiles indicated that ∼82% of 16 605 probes were within a twofold range difference between h-heps and c-heps. Cluster and principal component analyses showed that the gene expression patterns of c-heps were extremely similar to those of h-heps. In conclusion, the chimeric mouse livers were normally reconstructed with h-heps and m-HSCs, and expressed most human genes at levels similar to those in human livers, although the chimeric livers showed morphological characteristics typical of growth.

Steroid-free living donor liver transplantation for HCV--a multicenter prospective cohort study in Japan.

This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid-free IS protocol (Fr group) and 29 the traditional steroid-containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p=0.013). Preemptive anti-HCV therapy was started in a higher percentage of recipients (59.3%) in the Fr group than in the St group (31.0%, p=0.031), mainly due to early HCV recurrence. The incidence of HCV recurrence at one yr was lower in the Fr group (22.2%) than in the St group (41.4%; p=0.066). The incidence of acute cellular rejection was similar between groups. New onset diabetes after transplant, cytomegalovirus infection, and renal dysfunction were significantly less frequent in the Fr group than in the St group (p=0.022, p<0.0001, p=0.012, respectively). The steroid-free IS protocol safely reduced postoperative morbidity and effectively suppressed both the HCV viral load in the early post-transplant period and HCV recurrence in HCV-positive LDLT recipients.

Hepatic hyperplasia associated with discordant xenogeneic parenchymal-nonparenchymal interactions in human hepatocyte-repopulated mice.

Liver mass is optimized in relation to body mass. Rat (r) and human (h) hepatocytes were transplanted into liver-injured immunodeficient mice and allowed to proliferate for 3 or 11 weeks, respectively, when the transplants stopped proliferating. Liver/body weight ratio was normal throughout in r-hepatocyte-bearing mice (r-hep-mice), but increased continuously in h-hepatocyte-bearing mice (h-hep-mice), until reaching approximately three times the normal m-liver size, which was considered to be hyperplasia of h-hepatocytes because there were no significant differences in cell size among host (mouse [m-]) and donor (r- and h-) hepatocytes. Transforming growth factor-beta (TGF-beta) type I receptor, TGF-beta type II receptor, and activin A type IIA receptor mRNAs in proliferating r-hepatocytes of r-hep-mice were lower than in resting r-hepatocytes (normal levels) and increased to normal levels during the termination phase. Concomitantly, m-hepatic stellate cells began to express TGF-beta proteins. In stark contrast, TGF-beta type II receptor and activin A type IIA receptor mRNAs in h-hepatocytes remained low throughout and m-hepatic stellate cells did not express TGF-beta in h-hep-mice. As expected, Smad2 and 3 translocated into nuclei in r-hep-mice but not in h-hep-mice. Histological analysis showed a paucity of m-stellate cells in h-hepatocyte colonies of h-hep-mouse liver. We conclude that m-stellate cells are able to normally interact with concordant r-hepatocytes but not with discordant h-hepatocytes, which seems to be at least partly responsible for the failure of the liver size optimization in h-hep-mice.

Therapeutic potential of propagated hepatocyte transplantation in liver failure.

BACKGROUND: This study aimed to evaluate the therapeutic potential of intrasplenic transplantation of culture-propagated homologous hepatocytes in rats suffering from acute liver failure (ALF). METHODS: ALF was induced in dipeptidyl peptidase IV-negative (DPPIV(-)) Fischer 344 rats by totally removing the two anterior liver lobes (68% of the liver) and ligating the pedicle of the right lobe (24% of the liver). Hepatocytes isolated from DPPIV(+) Fischer 344 rats were cultured for 11 d to propagate 3-fold, and the resulting hepatocytes were dubbed "culture-propagated hepatocytes (CPHEPs)". A total of 1.5 × 10(7) cells of CPHEPs were transplanted intrasplenically before ALF induction (CPHEP group). Similarly, freshly isolated hepatocytes (FIHEPs) were transplanted as a positive control (FIHEP group), and culture medium (CM) was injected into rats as a negative control (CM group). RESULTS: The survival of the CPHEP group was comparable to that of the FIHEP group and longer than that of the CM group (P < 0.01). Both CPHEP and FIHEP transplantation improved blood parameters such as ammonia, total bilirubin, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase; transplantation also affected liver tissue parameters such as apoptosis rate and bromodeoxyuridine-labeling index. CONCLUSIONS: Transplantation of culture-propagated homologous hepatocytes has a remarkable therapeutic potential for ALF in rats.

Treatment strategy for early hepatocellular carcinomas: comparison of radiofrequency ablation with or without transcatheter arterial chemoembolization and surgical resection.

BACKGROUND: The preferred choice between surgical treatment and radiofrequency ablation (RFA) for the treatment of small resectable hepatocellular [corrected] carcinoma (HCC) has become a subject for debate. METHODS: We compared the results of hepatic resection (n = 199) with those of RFA (n = 87), of which 69 patients were treated with transcatheter arterial chemoembolization followed by RFA, for 286 patients with 3 or fewer nodules, none of which exceeded 3 cm in diameter at Hiroshima University Hospital. RESULTS: In subgroup analysis of single HCC with tumor size exceeding 2 cm in Child-Pugh class A, the disease-free survival time was significantly longer in the surgical resection group than in the RFA group (P = 0.048). In the subgroups of a single and multiple HCC with tumor size ≤2 cm in Child-Pugh class A, the overall and disease-free survival rates were almost the same for the surgical resection and RFA groups (P = 0.46 and 0.58, respectively, in single HCC, and P = 0.98 and 0.98, respectively, in multiple HCC). CONCLUSION: Surgical resection may provide better long-term disease-free survival than RFA in the subgroup of a single HCC exceeding 2 cm of Child-Pugh class A.

The Association between Wearing a Mask and COVID-19.

With the widespread and increasing number of cases of Coronavirus Disease (2019) globally, countries have been taking preventive measures against this pandemic. However, there is no universal agreement across cultures on whether wearing face masks are an effective physical intervention against disease transmission. We investigated the relationship between mask wearing and COVID-19 among close contacts of COVID-19 patients in the Hiroshima Prefecture, Japan. In the Hiroshima Prefecture, a COVID-19 form adapted from the reporting form, "Japanese Surveillance in Post-Extreme Emergencies and Disasters", was developed to collect data from COVID-19 patients' close contacts under active epidemiological surveillance at Public Health Centers. The relative risk of COVID-19 for mask users versus non-mask users was calculated. A total of 820 interviewees were included in the analysis and 53.3% of them responded that they wore masks. Non-mask users were infected at a rate of 16.4%, while mask users were infected at a rate of 7.1%. Those who wore masks were infected at a rate of 0.4 times that of those who did not wear masks. (RR = 0.4, 95%CI = 0.3-0.6; Adjusted RR = 0.6, 95%CI = 0.3-0.9). These findings implied that COVID-19 could be avoided to a certain degree by wearing a mask.

Heme induces ubiquitination and degradation of the transcription factor Bach1.

The transcription repressor Bach1 is a sensor and effector of heme that regulates the expression of heme oxygenase 1 and globin genes. Heme binds to Bach1, inhibiting its DNA binding activity and inducing its nuclear export. We found that hemin further induced the degradation of endogenous Bach1 in NIH 3T3 cells, murine embryonic fibroblasts, and murine erythroleukemia cells. In contrast, succinylacetone, an inhibitor of heme synthesis, caused accumulation of Bach1 in murine embryonic fibroblasts, indicating that physiological levels of heme regulated the Bach1 turnover. Polyubiquitination and rapid degradation of overexpressed Bach1 were induced by hemin treatment. HOIL-1, an ubiquitin-protein ligase which recognizes heme-bound, oxidized iron regulatory protein 2, was found to bind with Bach1 when both were overexpressed in NIH 3T3 cells. HOIL-1 stimulated the polyubiquitination of Bach1 in a purified in vitro ubiquitination system depending on the intact heme binding motifs of Bach1. Expression of dominant-negative HOIL-1 in murine erythroleukemia cells resulted in higher stability of endogenous Bach1, raising the possibility that the heme-regulated degradation involved HOIL-1 in murine erythroleukemia cells. These results suggest that heme within a cell regulates the polyubiquitination and degradation of Bach1.

Comparison of immunohistochemistry assays and real-time reverse transcription-polymerase chain reaction for analyzing hormone receptor status in human breast carcinoma.

The estrogen receptor (ER) and progesterone receptor (PgR) status of 163 surgical breast cancer specimens determined on real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using frozen tumor tissue were compared with that determined using three automated immunohistochemistry (IHC) assays including Dako (Glostrup, Denmark), Ventana (Tucson, AZ, USA) and BioGenex (San Ramon, CA, USA) assay. All specimens were semiquantified according to the Allred score and J-score. The cut-offs for ER determined by log (ER/glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) were -3.6 and -3.2 based on the Allred score and J-score, respectively, and those for PgR determined by log (PgR/GAPDH) were -3.2 and -2.8, respectively. The Allred total score (TS) and the J-score for ER and PgR on IHC were significantly correlated with the result on RT-PCR (P < 0.00001). There was a high degree of concordance among ER and PgR status on IHC and those on RT-PCR, suggesting that RT-PCR is a useful method for evaluation of ER and PgR status. Some discrepancies between the IHC and RT-PCR results were identified, however. Accordingly, further studies of RT-PCR assays for hormone receptor (HR) are necessary with regard to biological behavior and responsiveness to hormone therapy.

Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P < 0.001). Furthermore, the PLT count of patients with thrombocytopenia (PLT count or= 400), persistent thrombocytopenia is predictable after LTx.

Synthetic bioabsorbable stent material for duct-to-duct biliary reconstruction.

Biliary stricture remains a significant cause of morbidity after liver transplantation. We performed duct-to-duct biliary anastomosis by using an absorbable stent tube with a diameter equal to that of pig common bile duct as an internal stent. The stent tube was constructed using a synthetic biodegradable material-a lactic glycolic acid and epsilon-caprolactone copolymer. Three pigs were alive without cholestasis for 180 d; however, 1 pig died on the 65th postoperative d, and autopsy revealed no cholestasis or biliary sledge in the biliary stent tube. The 3 pigs were euthanized for histological examinations 180 d after surgery; the biliary stent tube was completely absorbed by this time. These experimental results showed the good patency of the absorbable biliary stent tube. In the future, the absorbable biliary stent tube is expected to be clinically developed as a biliary stent for biliary anastomosis, which may protect the biliary anastomotic stricture.

Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions.

h-prune, which has been suggested to be involved in cell migration, was identified as a glycogen synthase kinase 3 (GSK-3)-binding protein. Treatment of cultured cells with GSK-3 inhibitors or small interfering RNA (siRNA) for GSK-3 and h-prune inhibited their motility. The kinase activity of GSK-3 was required for the interaction of GSK-3 with h-prune. h-prune was localized to focal adhesions, and the siRNA for GSK-3 or h-prune delayed the disassembly of paxillin. The tyrosine phosphorylation of focal adhesion kinase (FAK) and the activation of Rac were suppressed in GSK-3 or h-prune knocked-down cells. GSK-3 inhibitors suppressed the disassembly of paxillin and the activation of FAK and Rac. Furthermore, h-prune was highly expressed in colorectal and pancreatic cancers, and the positivity of the h-prune expression was correlated with tumor invasion. These results suggest that GSK-3 and h-prune cooperatively regulate the disassembly of focal adhesions to promote cell migration and that h-prune is useful as a marker for tumor aggressiveness.

Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness.

Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.

A new technique for reconstruction of the middle hepatic vein without graft interposition: "the digging technique".

Ill-located liver metastases close to the cavo-hepatic confluence often require resection and reconstruction of hepatic veins. However, most of the current techniques for reconstruction of the hepatic veins require graft interposition or complex venoplasty. The present case report describes a new surgical procedure which allows reconstructing the middle hepatic vein (MHV) by direct end-to-end anastomosis after a right hepatectomy for colorectal liver metastases invading the right and middle hepatic veins. This technique is called the "digging technique", in which an additional atypical resection of a part of segment 4a "digging" around the distal end of the MHV in order to further mobilize the liver and to achieve, with an upward lifting of the remnant liver, a tension-free end-to-end reconstruction of the MHV. The immediate postoperative course was uneventful. After 6 months of follow-up the patient was well and the MHV was patent. In selected patients with liver metastases close to the MHV-inferior vena cava confluence, requiring a right hepatectomy, the "digging technique" allows a safe direct end-to-end anastomosis avoiding graft interposition.

Role of invariant natural killer T cells in liver sinusoidal endothelial cell-induced immunosuppression among T cells with indirect allospecificity.

We have previously demonstrated that liver sinusoidal endothelial cells (LSECs) that endocytose portally injected allogeneic cells exert immunosuppressive effects on T cells with indirect allospecificity. In this study, we have demonstrated that invariant natural killer T cells plays a significant role in such immunosuppressive effects induced by LSECs. The endocytic activity of LSECs toward intraportally injected splenocytes from B6 major histocompatibility complex class II-deficient C2ta (C2D) mice was markedly impaired in BALB/c CD1d-deficient mice. The intraportal adoptive transfer of LSECs isolated from BALB/c wild-type mice treated with a portal injection of B6 C2D splenocytes into BALB/c mice significantly prolonged the survival of subsequently transplanted heart allografts; however, the transfer of LSECs isolated from similarly treated BALB/c CD1d-deficient mice did not produce such a survival prolonging effect. These findings indicate that natural killer T cells are required for the LSEC-induced immune modulation of T cells with indirect allospecificity.

Effect of aerobic exercise training on oxidative stress in patients with type 2 diabetes mellitus.

The purpose of this study was to determine whether moderate-intensity exercise training reduces oxidative stress in patients with type 2 diabetes mellitus over 12 months. The patients were divided into 3 groups: aerobic training combined with the use of a fitness center (group A, n = 43), aerobic training only (group B, n = 44), or controls (group C, n = 16). The subjects in groups A and B were instructed to exercise at 50% of peak oxygen uptake for more than 30 minutes on at least 3 days per week over a 12 month period. In addition, the subjects in group A were instructed to use a fitness center and were taught how to perform aerobic training in the indicated manner by certified fitness instructors. We measured the levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a parameter of oxidative stress. Serum glycated albumin levels were reduced significantly after 6 and 12 months in groups A and B and after 12 months in group C. Urinary 8-OHdG levels decreased after 12 months in groups A and B, but remained unchanged in group C. There was a significant positive linear association between percentage changes in urinary 8-OHdG and glycated albumin levels over the 12 months. In conclusion, aerobic exercise training improved glycemic control and reduced oxidative stress in patients with type 2 diabetes mellitus. Furthermore, improvement in glycemic control was associated with a reduction in oxidative stress.

Engraftment of human hepatocytes in the livers of rats bearing bone marrow reconstructed with immunodeficient mouse bone marrow cells.

BACKGROUND: Previously, we created, a chimeric mouse (humanized mouse), a severe combined immunodeficiency (SCID) mouse whose liver was >90% repopulated with human (h)-hepatocytes, which are useful for the testing of drug metabolism and toxicity, as well as a hepatitis B virus and hepatitis C virus-susceptible animal model. However, their small body size and small total blood volume limited the utilization for analytical purposes, which led us to develop a method to create a chimeric rat bearing h-hepatocyte-repopulated liver. METHODS: F344 nude rats devoid of T cells were irradiated with X-rays and injected with bone marrow cells (BMCs) from SCID mice (m(SCID)). The rate of replacement with m(SCID)-BMCs was evaluated by two-color flow cytometry analysis of peripheral blood mononuclear cells (PBMCs). After m(SCID)-BMCs repopulated the host bone marrow (BM), the rats were treated with retrorsine, partially hepatectomized (PHx), and transplanted with 5 x 10(6) h-hepatocytes isolated from the chimeric mice. h-Albumin (h-Alb) concentrations in the host blood and the expression levels of protein and mRNA of hepatocyte differentiation markers in the h-hepatocytes were evaluated by ELISA, immunostaining, and reverse transcription-PCR, respectively. RESULTS: The m(SCID)-BMCs successfully repopulated the rats, the percentage of mouse cells reaching 94% among host (r(nudeF344)) PBMCs at 4 weeks after m-BMC transplantation. h-Hepatocytes isolated from the chimeric mice were transplanted to the liver of the m(SCID)-BMC-repopulated rats. The engrafted h-hepatocytes expressed h-Alb and h-cytochrome P450 (CYP) subtypes and survived showing normal phenotypes until at least 3 weeks post-h-hepatocytes transplantation (h-HPCT). However, the blood concentrations of h-Alb declined at 4 weeks post-HPCT, concomitant with the emergence of both r(nudeF344)- and m(SCID)-macrophages, suggesting the rejection of h-hepatocytes due to the activation of macrophages. CONCLUSION: We developed a novel method to create a rat that bears the liver engrafted with h-hepatocytes, utilizing a rat with the BM composed of m(SCID)-BMCs as a host. This h-hepatocyte-bearing rat will be a valuable model for studying the immunologic mechanisms involved in xenogeneic transplantation and for generating rats with higher rates of repopulation with h-hepatocytes.

JAMP, a Jun N-terminal kinase 1 (JNK1)-associated membrane protein, regulates duration of JNK activity.

We report the identification and characterization of JAMP (JNK1 [Jun N-terminal kinase 1]-associated membrane protein), a predicted seven-transmembrane protein that is localized primarily within the plasma membrane and associates with JNK1 through its C-terminal domain. JAMP association with JNK1 outcompetes JNK1 association with mitogen-activated protein kinase phosphatase 5, resulting in increased and prolonged JNK1 activity following stress. Elevated expression of JAMP following UV or tunicamycin treatment results in sustained JNK activity and a higher level of JNK-dependent apoptosis. Inhibition of JAMP expression by RNA interference reduces the degree and duration of JNK activation and concomitantly the level of stress-induced apoptosis. Through its regulation of JNK1 activity, JAMP emerges as a membrane-anchored regulator of the duration of JNK1 activity in response to diverse stress stimuli.

Comparative study of the Japan Integrated Stage (JIS) and modified JIS score as a predictor of survival after hepatectomy for hepatocellular carcinoma.

BACKGROUND: The purpose of the study was to compare the abilities of the JIS and modified JIS (m-JIS) scores to predict survival after hepatectomy for hepatocellular carcinoma (HCC). METHODS: Data for patients who underwent hepatectomy for HCC at Hiroshima University Hospital between 1986 and 2006 were included. The overall survival and disease-free survival were calculated by the Kaplan-Meier method, and differences between groups were tested by the log-rank test. The statistics of the Akaike information criterion (AIC) were used to show the more appropriate model. RESULTS: A total of 626 patients were included (male/female, 468/158; mean age, 63.4+/-9.6 years; Child-Pugh class A/B, 524/102; liver damage grade A/B/C, 356/261/9). Mean survival and disease-free survival were 8.04+/-0.39 and 4.69+/-0.32 years, respectively. There was a significant difference in the overall survival rate between JIS scores 1 and 2, and 2 and 3 (P<0.05), but not between scores 0 and 1, or 3 and 4 (P>0.05). Except between m-JIS scores 0 and 1, there was excellent discriminatory ability in overall survival rate between other consecutive groups. Concerning disease-free survival, a significant difference was found only between JIS scores 1 and 2. However, the disease-free survival rate could be well differentiated between m-JIS scores 1 and 2, and 3 and 4. The m-JIS score had a higher discriminatory ability, indicated by a linear trend analysis, and a higher homogeneity likelihood ratio, and lower AIC statistics, than the original JIS score in predicting both overall and disease-free survival. CONCLUSIONS: The modified-JIS scoring system using liver damage grade is better than the original JIS scoring system in predicting survival after hepatectomy for HCC in Japan.

Beneficial effects of living-donor liver transplantation on esophageal varices.

BACKGROUND: Liver transplantation (LT) is known to improve bleeding esophageal varices (EVs) and portal hypertension. However, many issues related to EVs after LT remain unresolved, such as whether LT reduces blood supply to EVs, improves the diameter of unruptured EVs, or improves or worsens EVs. The aim of this retrospective study was to determine the effects of living-donor liver transplantation (LDLT) in patients with hepatic failure on EVs and inflow vessels to EVs and the factors associated with deterioration of EVs after LDLT. METHODS: The study subjects were 35 patients with cirrhosis who underwent LDLT. Endoscopy and multidetector helical computed tomography (MDCT) were performed before and after LDLT. The diameter of the inflow vessel of EVs was measured by MDCT before and after LDLT, together with the LDLT-related reduction rate of the diameter of the gastric vein (RRGV). RESULTS: Endoscopic examination showed improvement of EVs in 30 of 35 (86%) patients. RRGV improved in 17/35 (49%) patients, did not change in 13/35 (37%), and deteriorated in 5/35 (14%). The cause of RRGV deterioration seemed to be either the complication of portal vein or graft failure. In patients examined endoscopically at >1 year after LDLT, improvement of EVs was associated with significant changes in the rate of reduction of the major inflow vessel diameter and Child-Pugh score, compared with those who showed no improvement. CONCLUSIONS: LDLT results in improvement of EVs. EVs improved in 86% of the patients. Measurement of RRGV with MDCT is a good tool for prediction of EV improvement after LDLT.

Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: It is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC. METHODS: The study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (> or =70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again. RESULTS: Higher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 x 10(4)/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis. CONCLUSIONS: The elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.