Search

The "community cat program (CCP)" is a non-lethal control measure in which stray cats are owned and cared for as community cats at high welfare standards, while the Trap-Neuter-Return (TNR) or Trap-Test-Vaccinate-Alter-Return-Monitor (TTVARM) event is performed. The program is recommended by the Ministry of the Environment in Japan. Here, we evaluated the health status of community cats inhabiting a tourist area in Onomichi City. A medical check was conducted on 30 community cats as a part of the TTVARM event. The following health problems were identified: alopecia, gingivitis, incisor teeth loss, anemia, and urine glucose. An ELISA (the enzyme linked immunosorbent assay) showed that 16.7% of the cats were FIV-positive. The cats were also carriers of zoonoses (Capnocytophaga genus (100%) and Bartonella henselae (ITS, nested; 38.0%)), which pose a risk to tourists and residents. Our findings suggest that most cats require medical treatment. We recommend that friendly cats should be adopted rather than maintained as community cats and that a comprehensive review of the CCP is required.

The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined. Overall, 250 patients (median age 71 years; range 30–87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5–38.0; P = 0.0002) and ipilimumab–nivolumab combination therapy (OR 61.2; 95% CI 7.9–1275.3; P

AIM Diagnosis of primary biliary cholangitis (PBC), which recurs in approximately 30% of liver transplant recipients, is histology-based, but no staging system has been established for recurrent PBC (rPBC). We used the Nakanuma staging system and cytokeratin 7 (CK7) staining to examine post-transplant liver biopsy specimens retrospectively and to evaluate histological features of rPBC. METHODS From 107 patients who underwent living donor liver transplantation for PBC, 60 recipients with 214 liver biopsies after 1-year post transplant were enrolled. Fibrosis, bile duct loss (BL), cholangitis activity, hepatitis activity, and CK7-positive hepatocytes were scored. Nakanuma staging was based on fibrosis and BL scores. We examined the correlation of scores and clinicolaboratory data among rPBC patients. We also evaluated whether chronological change of stage was correlated with liver-related failure. RESULTS Of 214 biopsies, 52 were protocol biopsy; 162 were episodic. Higher BL, cholangitis activity, and hepatitis activity scores were associated with rPBC diagnosis. At median follow up of 10.0 years (range 1.4-18.7 years), 29 (48%) patients were diagnosed with rPBC at 4.6 years (range 1.3-14.5 years). Liver-related failure occurred in five rPBC cases; three from rPBC, and two from chronic rejection. At rPBC diagnosis, higher BL and CK7 scores were more frequent in patients who developed liver-related failure than in other patients (P = 0.04, P

Hepatocellular carcinoma (HCC) developing after hepatitis C virus (HCV) eradication is a serious clinical concern. However, molecular basis for the hepatocarcinogenesis after sustained virologic response (SVR) remains unclear. In this study, we aimed to unveil the transcriptomic profile of post-SVR liver tissues and explore the molecules associated with post-SVR carcinogenesis. We analysed 90 RNA sequencing datasets, consisting of non-cancerous liver tissues including 20 post-SVR, 40 HCV-positive and 7 normal livers, along with Huh7 cell line specimens before and after HCV infection and eradication. Comparative analysis demonstrated that cell cycle- and mitochondrial function-associated pathways were altered only in HCV-positive non-cancerous liver tissues, whereas some cancer-related pathways were up-regulated in the non-cancerous liver tissues of both post-SVR and HCV-positive cases. The persistent up-regulation of carcinogenesis-associated gene clusters after viral clearance was reconfirmed through in vitro experiments, of which, CYR61, associated with liver fibrosis and carcinogenesis in several cancer types, was the top enriched gene and co-expressed with cell proliferation-associated gene modules. To evaluate whether this molecule could be a predictor of hepatocarcinogenesis after cure of HCV infection, we also examined 127 sera from independent HCV-positive cohorts treated with direct-acting antivirals (DAAs), including 60 post-SVR-HCC patients, and found that the elevated serum Cyr61 was significantly associated with early carcinogenesis after receiving DAA therapy. In conclusion, some oncogenic transcriptomic profiles are sustained in liver tissues after HCV eradication, which might be a molecular basis for the liver cancer development even after viral clearance. Among them, up-regulated CYR61 could be a possible biomarker for post-SVR-HCC.

An 80-year old man with myelofibrosis and chronic renal disease was admitted to our hospital because of severe anemia and gastrointestinal bleeding. Although no bleeding was observed by upper or lower endoscopy, contrast-enhanced computed tomography revealed an enhanced area in the small intestinal wall that was suspected of being the bleeding site, and was confirmed by double-balloon endoscopy. Based on endoscopic findings, it was difficult to differentiate between variceal rupture and collapse of a submucosal tumor. We performed segmental resection of the small intestine to make a definitive diagnosis and achieve reliable hemostasis. The gross findings confirmed a variceal rupture from the small intestine. His gastrointestinal bleeding stopped and his anemia improved following surgery. Although some cases of portal hypertension in association with myelofibrosis have been reported, we are aware of no prior reports of variceal rupture in the small intestine. To our knowledge, this is the first reported case of ectopic jejunal varices in a patient with myelofibrosis.

Beta-catenin-activated hepatocellular adenoma is potentially malignant and warrants careful follow-up and surgical resection. Here, we report a 48-year-old man in whom a 55 mm single liver tumor was incidentally detected in the S1 segment. Contrast-enhanced computed tomography scans showed no enhancement in the early phase and a slight defection in the late phase. The tumor was enhanced hyperintensity in the hepatobiliary phase on Gd-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging. The histologic features of ultrasound-guided fine-needle aspiration biopsy indicated hepatocellular adenoma, and the tumor was immunohistochemically positive for glutamine synthetase and β-catenin. Considering the risk of malignant transformation, he underwent laparoscopic-assisted partial liver resection. The resected tumor did not contain any malignant lesions. This case indicates that aspiration needle biopsy and immunohistochemistry were useful for histological diagnosis and treatment decisions based on the molecular definition of hepatocellular adenoma.

A 72-year-old man underwent transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) located on the S6 segment. He had a history of anti-viral therapy for hepatitis C virus and was being treated for diabetes mellitus with inadequate control. On day 28 after TACE, he visited our hospital again, with complaints of fever and abdominal pain in the right upper quadrant. Blood examination showed elevated levels of white blood cells and C-reactive protein. Computed tomography showed a poorly marginated, low-density lesion measuring 9.5 x 8.0 x 4.0 cm, forming multiple small gas bubbles, located superiorly, and in contact with HCC treated by TACE. Ultrasound-guided puncture revealed whiffy and muddy pus. Gram staining of the pus showed the presence of numerous gram-positive rods, which were identified as Cutibacterium namnetense. He underwent percutaneous trans-hepatic abscess drainage and received antibiotics treatment. The abscess was successfully treated, and he was discharged on day 19. The incidence of liver abscess after TACE is rare, and intestinal microbiota have been reported to be the common pathogens. To the best of our knowledge, this is the first case of liver abscess caused by Cutibacterium namnetense.

Portal vein thrombosis is caused by various diseases, including liver cirrhosis, cancer, abdominal infection, and myeloproliferative disorders. Essential thrombocythemia is one of the myeloproliferative disorders in which the bone marrow produces excessive amount of platelets and can be accompanied by various thrombotic diseases; however, essential thrombocythemia with limited cutaneous systemic sclerosis has not been reported yet. We herein report a case of extensive portal vein thrombosis due to essential thrombocythemia with limited cutaneous systemic sclerosis. A 49-year-old woman was referred to our hospital due to liver dysfunction. Extended portal vein thrombosis, splenomegaly, and thrombocytosis were founded. The examination of Janus kinase 2 V617F mutation in the bone marrow was positive. These findings resulted in the diagnosis of portal vein thrombosis due to essential thrombocythemia. Furthermore, Raynaud's phenomenon, finger's sclerosis, and positive anti-centromere antibody led to limited cutaneous systemic sclerosis. To further analyze the causal relationship between essential thrombocythemia and limited cutaneous systemic sclerosis, platelet-derived growth factor was examined. High level of serum platelet-derived growth factor, possibly caused by high platelet count due to essential thrombocythemia, was observed. As platelet-derived growth factor has been reportedly associated with the occurrence of systemic sclerosis, the present case indicates the possible causal link between essential thrombocythemia and limited cutaneous systemic sclerosis through high platelet-derived growth factor.

Hepatitis-associated aplastic anemia (HAAA) is a variant of acquired aplastic anemia and characterized by bone marrow failure that follows the development of acute hepatitis. We herein report a rare case of HAAA with rapid progression of liver fibrosis due to repeated hepatitis. A pathological examination of liver specimens revealed liver fibrosis progression over a short period. Immunosuppressive therapy with cyclosporine effectively cured both the pancytopenia and hepatitis. Our case suggests that the pathological examination of the liver tissue is useful for determining a treatment plan and that immunosuppressive therapy is a promising treatment for both aplastic anemia and persistent hepatitis.

Abatacept, a cytotoxic T lymphocyte antigen-4 immunoglobulin recombinant fusion protein, is an immunosuppressive agent indicated for rheumatoid arthritis. Although no significant increase in malignancy has been reported in abatacept-treated patients, whether or not abatacept accelerates tumor progression in specific cancer types remains unclear. We herein report a 66-year-old woman who showed unusually rapid progression of hepatocellular carcinoma following abatacept therapy for rheumatoid arthritis. Abatacept was speculated to have accelerated her hepatocellular carcinoma progression in the setting of her preexisting risk factors: autoimmune hepatitis and long-term methotrexate use. We propose close tumor surveillance be performed during abatacept therapy, especially for high-risk patients.

Aim In cases of symptomatic giant hepatic cysts, appropriate treatment is required to relieve symptoms. Ethanol, minocycline hydrochloride, and ethanolamine oleate have been conventionally used for ultrasound (US)-guided sclerotherapy. However, liquid sclerosing agents could mix with the residual fluid in the cyst and reduce their sclerotic effects. We carried out US-guided microfoam sclerotherapy using polidocanol for three patients and evaluated its efficacy and safety. Methods Between May 2016 and March 2017, three female patients with symptomatic giant hepatic cysts were referred to our hospital. All of them were prospectively included in this study. Results The maximum diameters of the hepatic cysts in the three patients were 92 × 89 × 86 mm, 155 × 119 × 140 mm, and 223 × 195 × 123 mm, respectively. Polidocanol microfoam was successfully administered through an 8.5-Fr pigtail catheter for all patients. One, two, and three microfoam sclerotherapy sessions were undertaken according to the initial cyst volume for cases 1, 2, and 3, respectively. The mean reduction rates of the cyst volume were 90.1% (85.5-98.9%) at 3 months, 96.3% (91.9-99.9%) at 6 months, and 99.5% (99.1-99.9%) at 9 months after treatment. No significant treatment-induced adverse effects were observed. Conclusion Ultrasound-guided microfoam sclerotherapy using polidocanol could be an effective and safe method for the treatment of symptomatic giant liver cysts.

OBJECTIVE To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT). BACKGROUND Donor age is a well-known prognostic factor in deceased donor liver transplantation; however, its role in LDLT remains unclear. METHODS We retrospectively analyzed 315 consecutive cases of primary adult-to-adult LDLT in our center between April 2006 and March 2014. Recipients were divided into 5 groups according to the donor age: D-20s (n = 60); D-30s (n = 72); D-40s (n = 57); D-50s (n = 94); and D-60s (n = 32). The recipient survival and the association with various clinical factors were investigated. RESULTS Recipient survival proportions were significantly higher in D-20s compared with all the other groups (P = 0.008, < 0.001, < 0.001, and = 0.006, vs D-30s, -40s, -50s, and -60s, respectively), whereas there was no association between recipient survival and their own age. There are 3 typical relationships between donors and recipients in adult-to-adult LDLT: from child-to-parent, between spouses/siblings, and from parent-to-child. The overall survival in child-to-parent was significantly higher than in spouses/siblings (P = 0.002) and in parent-to-child (P = 0.005), despite significantly higher recipient age in child-to-parent [59 (42-69) years, P < 0.001]. Contrastingly, parent-to-child exhibited the lowest survival, despite the youngest recipient age [26 (20-43) years, P < 0.001]. In addition, younger donor age exhibited significantly better recipient survival both in hepatitis C virus-related and in non-hepatitis C virus diseases. Univariate and multivariate analyses both demonstrated that donor age and graft-type (right-sided livers) are independent prognostic factors for recipient survival. CONCLUSIONS Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.

BACKGROUND AND AIM Mac-2-binding protein glycosylation isomer (M2BPGi) was recently identified as a serum glycobiomarker for liver fibrosis. However, the relationship between M2BPGi and malnutrition in patients with chronic liver disease (CLD) is unknown. We aimed to evaluate whether M2BPGi could be a surrogate marker for malnutrition in patients with CLD. METHODS In total, 338 outpatients with CLD were enrolled (median age: 67 years). We evaluated the associations among liver fibrosis markers (M2BPGi, fibrosis-4 index, and aspartate aminotransferase-to-platelet count ratio index), Child-Pugh stages, and nutritional status markers. RESULTS The median value (range) of serum M2BPGi levels was 0.94 cut-off index (COI) (0.22-11.57) in chronic hepatitis and Child-Pugh A (n = 274), 4.775 COI (1.32-16.68) in Child-Pugh B (n = 46), and 11.37 COI (6.03-18.33) in Child-Pugh C (n = 18) (overall significance, P

Background and Objectives Health Care Workers (HCWs) are at a high risk of needle stick injuries and HBV infection in Egypt; this problem is further aggravated by low Hepatitis B (HB) vaccination coverage. Limited data are available on the prevalence of HBV infection in Egyptian HCWs. In this study, we aimed to assess the HBV infection rate and genotypes among Egyptian HCWs. Methods Five hundred and sixty-four (564) HCWs were included. Of them, 258 (45.74%) were health care providers and 306 (54.25%) were non-health care providers. All HCWs completed both the study questionnaires and provided a blood sample for HBV testing. Indeed, all HCWs were tested for Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B core antigen (anti-HBc), by enzyme-linked immunosorbent assay. HBVDNA was checked for HCWs who tested positive for HBsAg and/or anti-HBc, by nested Polymerase Chain Reaction (PCR). HBVDNA positive HCWs were further subjected to HBV genotyping. Results The mean age of included HCWs was 33.0 ± 9.8 years, of whom 319 (56.56%) were males. The mean duration of health care work was 9.3 ± 6.7 years. The frequency of HBsAg and anti-HBc were 1.4%, and 24.5%, respectively. Old age and prolonged duration of health care work were significantly associated with anti-HBc seropositivity. Among 140 HCWs positive for HBsAg and/or anti-HBc, 14 (10 %) had positive HBVDNA by PCR. HBV/E (n = 7), HBV/D (n = 3) and co-infection with E and D (n = 4) genotypes were detected. Conclusion Egyptian HCWs have a significantly high rate of HBV exposure. The detection of HBV/E genotype among Egyptian HCWs suggests prevalent transmission of HBV/E among Egyptian populations.

Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a treatment switch to tyrosine kinase inhibitors (TKIs) needs to be considered. However, TACE could worsen liver function, thereby narrowing the time window for a switch to TKIs because TKIs are recommended for patients with Child-Pugh grade A (CP-A). We investigated the factors associated with CP grade deterioration after TACE. Among patients who underwent TACE, 125 patients with CP-A were enrolled. The cumulative CP grade deterioration rates were 20.3%, 27.1%, and 41.4% at six months, one year, and two years, respectively. Multivariate analysis revealed that factors associated with CP grade deterioration included high Mac-2 binding protein glycosylation isomer (M2BPGi) levels (&gt, 2.00 cut-off index) and beyond the up-to-seven criteria. The cumulative CP grade deterioration rates of patients with high M2BPGi and beyond the up-to-seven criteria were 50.6% and 59.2% at six months and one year, respectively, which were significantly higher than for those in any other groups. The combination of M2BPGi and up-to-seven criteria could be a surrogate marker for predicting CP grade deterioration after TACE. In patients with intermediate-stage HCC, elevated M2BPGi levels, and beyond the up-to-seven criteria, an early treatment switch to TKIs should be considered to improve their prognosis.

Efficacy of 8-week regimen with direct-acting antivirals (DAA) for patients with hepatitis C after liver transplantation has not been clarified. This study aimed to clarify the efficacy and safety of glecaprevir and pibrentasvir therapy for 8 and 12 weeks in Japanese patients with recurrent hepatitis C after liver transplantation. A cohort study of liver transplant recipients with recurrent hepatitis C treated with glecaprevir (300 mg/day) and pibrentasvir (120 mg/day) was performed at nine liver transplant centers in Japan. Twenty-five patients with hepatitis C after liver transplantation were treated with glecaprevir and pibrentasvir. Twenty-four patients completed the treatment protocol; treatment was discontinued in one patient who had nausea at 3 days after the initiation of treatment. All the 24 patients who completed the 8- or 12-week treatment protocol achieved a sustained virological response 12 weeks after completion of treatment (SVR12). The SVR12 rates in patients with HCV genotype 1 and 2 were 100% (21 of 21 patients) and 75% (3 of 4 patients), respectively. All patients with prior DAA therapy failure (n = 6), jaundice (n = 4), and liver cirrhosis (n = 4) achieved SVR12. Seven of 8 patients (88%) with severe renal impairment achieved SVR12. Adverse events occurred in 6 of 25 patients (24%), including serious adverse events in 2 patients (8%). Treatment-related adverse events were nausea, pruritus, and mild renal dysfunction. Eight- or 12-week regimen of glecaprevir and pibrentasvir is efficacious and safe in patients with recurrent HCV infection after liver transplantation, even in difficult-to-treat populations, including patients with severe renal impairment, prior DAA experience, liver cirrhosis, or jaundice after liver transplantation.

HBV reactivation could be induced under immunosuppressive conditions in patients with resolved infection. This study aimed to clarify the viral factors associated with the pathogenesis of HBV reactivation in association with the immunosuppressive status. Whole HBV genome sequences were determined from the sera of 24 patients with HBV reactivation, including 8 cases under strong immunosuppression mediated by hematopoietic stem cell transplantation (HSCT) and 16 cases without HSCT. Ultra-deep sequencing revealed that the prevalence of genotype B and the ratio of non-synonymous to synonymous evolutionary changes in the surface (S) gene were significantly higher in non-HSCT cases than in patients with HSCT. Those non-synonymous variants included immune escape (6/16 cases) and MHC class II-restricted T-cell epitope variants (6/16 cases). Furthermore, reactivated HBV in 11 of 16 (69%) non-HSCT cases possessed substitutions associated with impaired virion secretion, including E2G, L77R, L98V, T118K, and Q129H in the S region, and M1I/V in the PreS2 region. In conclusion, virologic features of reactivated HBV clones differed depending on the intensity of the immunosuppressive condition. HBV reactivation triggered by immunosuppressive conditions, especially those without HSCT, was characterized by the expansion of variants associated with immune escape, MHC class II-restricted T-cell epitope alterations, and/or impaired virion secretion.

Aim This study aimed to clarify the efficacy and safety of simeprevir, a second-generation NS3/4A inhibitor, with peginterferon and ribavirin for recurrent hepatitis C after liver transplantation. Methods A retrospective cohort study of living-donor liver transplant recipients with recurrent hepatitis C with the hepatitis C virus genotype 1 treated with either simeprevir- or telaprevir-based triple therapy was carried out at eight Japanese liver transplant centers. Results Simeprevir- and telaprevir-based triple therapies were given to 79 and 36 patients, respectively. Of the 79 patients treated with simeprevir-based triple therapy, 44 (56%) achieved sustained virological response 12 weeks (SVR12) after treatment ended, and there was no significant difference in the SVR12 between the simeprevir- and telaprevir-based triple therapy groups (69%). The rates of adverse events were not significantly different between the simeprevir- and telaprevir-based triple therapy groups, although the rate of patients who received blood cell transfusion and erythropoietin due to anemia and had renal insufficiency were significantly higher in the telaprevir group than in the simeprevir group. Three baseline factors, the presence of prior dual therapy with peginterferon and ribavirin (P = 0.001), a non-responder to the prior dual therapy (P

Background/Aims: Direct-acting antiviral agents (DAAs) have increased the sustained viral response rate with minimal adverse effects and short treatment duration. In addition, recent data suggest the possibility that hepatitis C virus (HCV) clearance results in rapid improvement in metabolic pathways. The aim of the present study was to evaluate whether the DAA treatment without ribavirin lowers hemoglobin A1c (HbA1c) at 12 weeks after therapy completion. Methods: We performed an observational study to assess the effect of sofosbuvir and ledipasvir (SOF/LED) treatment on glycemic control. We compared HbA1c levels before and after treatment with SOF/LED, considering that anemia is not a side effect of these drugs. Results: In the 36 patients with HCV eradication, HbA1c levels decreased significantly after treatment (pre-treatment 5.85% vs. post-treatment 5.65%, p < 0.01). Conclusion: This pilot study shows the possibility that HCV eradication by SOF/LED was accompanied by an improvement of glucose metabolism in the population with or without diabetes, and suggests further investigation.

AIM Recent advances in next-generation sequencing (NGS) technologies allow for evaluation of genetic alterations in various cancer-related genes in daily clinical practice. Archival formalin-fixed paraffin-embedded (FFPE) tumor tissue is often used for NGS-based clinical sequencing assays; however, the success rate of NGS assays using archival FFPE tumor tissue is reported to be lower than that using fresh tumor tissue. We aimed to evaluate the feasibility and safety of ultrasound (US)-guided liver tumor biopsy for NGS-based multiplex gene assays. METHODS We compared the success rate of NGS assays between archival FFPE tumor tissues and US-guided liver tumor biopsy tissues, and summarized the treatment progress of the patients. RESULTS Next-generation sequencing assays using US-guided liver biopsy samples were successful in all patients (22/22), whereas the success rate with archival FFPE tumor tissue was 84.8% (151/178, P

Prophylactic measures are used to reduce DNHB after HBsAg-negative patients receive anti-HBc-positive liver grafts. This study investigated the incidence of DNHB and clinical outcomes in pediatric LT recipients under HBIG prophylaxis, with or without hepatitis B vaccination. Between 1995 and 2013, 51 HBsAg-negative pediatric recipients underwent living-donor LT from anti-HBc-positive donors. The median (range) age was 4 (0.1-17) years, 23 (45%) were male, and 71% were negative for both anti-HBc and anti-HBc. During a median follow-up of 12.1 (0.06-19.9) years, 13 (25.4%) developed DNHB; 7 of the 13 achieved HBsAg seroconversion after administration of LAM or ETV. Among studied patients, 20 (39%) received hepatitis B vaccination, and 2 of them (10%) developed DNHB. At last follow-up, 41% (21/51) discontinued HBIG either after successful HBV vaccination (n = 17) or retransplantation with anti-HBc-negative grafts (n = 4). In conclusion, pediatric LT recipients of anti-HBc-positive grafts, most of them were naive to HBV infection, were at high risk of DNHB, and consistent monitoring for the early detection of DNHB was necessary. A combination use of post-LT vaccination is promising prophylactic strategy against DNHB.

Supplemental digital content is available in the text., Background Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease, with liver transplantation being the sole life-saving treatment for end-stage PSC-related liver disease. However, recurrence of PSC after liver transplantation is a common complication, with the risk factors for recurrence being controversial. Methods We conducted a retrospective chart review of 45 patients who had undergone liver transplantation for PSC at our institute. The risk factors for PSC recurrence and graft failure after liver transplantation were analyzed. Results The graft survival rates were 55.4% at 5 years and 32.8% at 10 years after liver transplantation for PSC. PSC recurrence was diagnosed in 16 (40%) of 40 patients, at a median 30 months (range, 9-70 months) after liver transplantation. The cumulative incidence rate of PSC recurrence was 24.5% at 3 years, 39.3% at 5 years, and 45.8% at 6 years. Among the 16 patients diagnosed with PSC recurrence, the graft survival rate was 56.3% at 5 years, and 21.9% at 10 years after the recurrence. Active inflammatory bowel disease after liver transplantation was identified as an independent risk factor for PSC recurrence. Age younger than 30 years at the time of PSC diagnosis and bacteremia were factors significantly associated with graft failure after liver transplantation on multivariate analysis. Conclusions PSC frequently recurred and progressed to graft failure after liver transplantation for PSC. Maintaining an inactive status of inflammatory bowel disease might offer protection against PSC recurrence.

Aim Hepatitis B virus (HBV) reactivation after liver transplantation in HBV patients, or in HBV negative recipients of anti-hepatitis B core (HBc) positive grafts, has been prevented by prophylactic use of hepatitis B immunoglobulin (HBIG) and/or nucleoside/nucleotide analogs (NA). Vaccination against HBV is an alternative that may provide a chance to discontinue prophylaxis by producing anti-hepatitis B surface (HBs) antibodies. Methods We retrospectively reviewed 40 HBV positive recipients (HBV+ group) and 27 HBV negative recipients of anti-HBc positive grafts (HBV−/anti-HBc+ graft group), who were administrated double-dose hepatitis B vaccination. Recipients were regarded as responders when anti-HBs greater than 100 IU/L was maintained for 6 months or more without HBIG. Response rates of vaccine and long-term outcomes were analyzed. Results Eighteen of the 40 patients in the HBV+ group (45%) and 18 of the 27 patients in the HBV−/anti-HBc+ graft group (67%) responded to vaccination after a median of four and three times, respectively. Younger age was the only independent factor associated with vaccine response in the HBV−/anti-HBc+ graft group (P = 0.03), whereas no factor was found to be an independent predictor for vaccine response in the HBV+ group. Among the 18 responders in the HBV+ group, 17 remained without NA or HBIG 8.2 years after the start of vaccination. Ten of those required periodic booster vaccination. All 18 responders in the HBV−/anti-HBc+ graft group remained free from HBV prophylaxis 6.2 years after the start of vaccination. Conclusion Younger recipients have a greater chance to develop sufficient anti-HBs after double-dose HBV vaccination, leading to discontinue HBV prophylaxis.

Epstein-Barr virus (EBV)-associated gastric carcinoma accounts for nearly 10% of all gastric carcinomas and has distinct demographic, clinical and pathological features compared with EBV-negative gastric carcinoma. We herein report the case of a patient with EBV-associated gastric carcinoma followed up for 12 years during the natural course of the disease. The appearance of the tumor on gastroscopy and computed tomography gradually changed, and the size of the lesion increased very slowly during the 12 years, without metastasis. The present case indicates that some EBV-associated gastric carcinomas progress very slowly.

Acetaminophen (paracetamol), a widely used antipyretic/analgesic, is a well-known agent causing acute hepatic injury. Whereas most cases are caused by its intrinsic hepatotoxicity, idiosyncratic hepatitis by the allergic mechanism is extremely rare. We herein report a case of late-onset acetaminophen-induced allergic hepatitis with progression to chronicity. This unique case extends the spectrum of acetaminophen-induced liver injury. Clinicians should be aware of this unusual clinical manifestation. The mechanism underlying the immunological reaction to acetaminophen remains to be elucidated.

Aim Alcoholic liver cirrhosis (ALC) is an established indication for liver transplantation (LT). Although the importance of preoperative abstinence is accepted, the optimal period of pretransplant abstinence is unclear. Our previous report in a Japanese cohort revealed a significant negative impact of recidivism on patient survival but failed to show significance of the length of pretransplant abstinence. The aim of this study was to evaluate the optimal period of pretransplant abstinence. Methods Subjects underwent LT for ALC (n = 195: 187 living donor liver transplantations, five deceased donor liver transplantations and three domino LT) in Japan from November 1997 to December 2011. Risk factors and the impact on outcome of alcohol relapse were analyzed in 140 patients, after excluding 26 patients with in-hospital mortality and 29 patients without information about alcohol relapse. Results The incidence of alcohol consumption after LT was 22.9% (32/140). The relapse time was within 18 months after LT in 24 patients, after 18 months in two patients and unknown in six patients. Alcohol-related damage occurred in 18 of the 24 patients with recidivism within 18 months. The patient survival rate of patients with harmful relapse was significantly lower than that of abstinent patients and patients with non-harmful relapse (P = 0.019). Preoperative abstinence shorter than 18 months was a significant indicator of the risk of harmful relapse (P = 0.009). High-risk alcohol relapse scores had no impact on the incidence. Conclusion Preoperative abstinence was an important predictor of post-transplant harmful relapse leading to inferior outcomes.

The optimal therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has not yet been established. This study aimed to clarify the efficacy and safety of interferon-free therapy with sofosbuvir and ledipasvir without ribavirin for 12 weeks in Japanese patients with HCV genotype 1b infection after living donor liver transplantation. A cohort study of living donor liver transplant recipients with recurrent HCV genotype 1b infection treated with sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was performed at six liver transplant centers in Japan. Fifty-four patients were treated with sofosbuvir and ledipasvir. Thirty-eight patients (70%) were treatment experienced, including 17 patients who had undergone prior direct-acting-antiviral-based triple therapy. Ten patients had resistance-associated substitutions at L31 or Y93 in the NS5A region of the HCV genome. Fifty-three patients completed the 12-week treatment protocol; treatment was discontinued in one patient who developed pneumonia at 4 weeks and died thereafter. All 53 patients who completed the treatment regimen achieved a sustained virological response 12 weeks after completion of treatment. Treatment was well tolerated in most patients, but seven patients developed serious adverse events, including hemorrhagic duodenal ulcers (n = 3), infection (n = 2), pleural effusion (n = 1), and alveolar hemorrhage (n = 1). Sofosbuvir and ledipasvir treatment without ribavirin for 12 weeks was highly effective in achieving a sustained virological response in Japanese patients who developed recurrent HCV genotype 1b infection after living donor liver transplantation.

Introduction Recent advances in next-generation sequencing (NGS) technologies allow for evaluation of genetic alterations in various cancer-related genes in daily clinical practice. Archival formalin-fixed paraffin-embedded (FFPE) tumor tissue is often used for NGS-based clinical sequencing assays; however, the success rate of NGS assays using archival FFPE tumor tissue is reported to be lower than that using fresh tumor tissue. We aimed to evaluate the feasibility and safety of Sonazoid-enhanced ultrasound (SEUS)-guided liver tumor biopsy for NGS-based multiplex gene assays. Methods We compared the success rate of NGS assays between archival FFPE tumor tissues and SEUS-guided liver tumor biopsy tissues, and summarized the treatment progresses of the patients. Results NGS assays using SEUS-guided liver biopsy samples were successful in all patients (22/22), whereas the success rate with archival FFPE tumor tissue was 84.8% (151/178, p Conclusion Our findings suggest that SEUS-guided liver tumor biopsy is a useful and safe method for obtaining high-quality samples for NGS-based clinical sequencing. In cases with metastatic liver tumors, SEUS-guided biopsy should be considered to provide accurate and optimal sequencing results for patients.

Introduction Recently, a multi-targeted tyrosine kinase inhibitor, lenvatinib, was approved as first-line therapy for unresectable hepatocellular carcinoma (HCC). Lenvatinib exerts antitumor activity by inhibiting angiogenesis through blockage of the VEGF and FGF pathway. Contrast-enhanced CT (CECT) is generally used for evaluation of therapeutic effect of lenvatinib; however, CECT is unsuitable for frequent monitoring. We aimed to evaluate the feasibility of Sonazoid-enhanced ultrasound (SEUS) for predicting therapeutic effect of lenvatinib. Methods Among patients with HCC who started treatment with lenvatinib in hour hospital, five cases who could receive time intensity curve (TIC) analysis by SEUS using LOGIQ E9 (GE Healthcare) were enrolled in this study. We compared the results of TIC analysis within 1 month after treatment initiation and first CECT after 2-3 months. Results The reduction rate of tumor blood flow by SEUS-TIC analysis within 1 month after treatment initiation and the evaluation of treatment response by first CECT after 2-3 months showed high correlation. However, SEUS-TIC analysis was applicable to limited cases who have a hypervascular nodule that can be visualized and measured stably with US and can stably hold breath. Conclusion Our findings suggest the utility of TIC analysis by SEUS for predicting therapeutic effect of lenvatinib against HCC in appropriate cases.

Plasma cell hepatitis (PCH) is an idiopathic disorder characterized by plasma cell infiltration in the allografts of patients who have undergone liver transplantation. Although an increasing number of cases of PCH have been reported in liver transplant recipients with hepatitis C recurrence treated with interferon, it is unclear whether PCH is induced by interferon itself. Here, we describe the cases of two patients who developed PCH just after the termination of antiviral therapy for recurrent hepatitis C after living donor liver transplantation. Liver dysfunction appeared at 1 month in one patient and 2 months in the other patient after pegylated interferon plus ribavirin therapy, and liver histology showed interface hepatitis with plasma cell-rich lymphoid aggregates. Both patients recovered after steroid therapy and achieved sustained virological response. These cases suggest that PCH could be induced by the alteration of the immune condition resulting from the termination of antiviral therapy. PCH should be considered when the transaminase levels increase after antiviral therapy, and it should be carefully distinguished from hepatitis C relapse.

Severe cholestatic hepatitis C (SCH) is a unique variant of recurrent hepatitis C that occurs after liver transplantation. Unfortunately, the prognosis of SCH is poor, and interferon (IFN) therapy has been reported to not improve the prognosis. We herein report a case of progressive SCH with acute cellular rejection (ACR) and bacterial infection, which was successfully treated using IFN-free therapy with daclatasvir and asunaprevir. A 43-year-old man was diagnosed with SCH and mild ACR at day 48 after liver transplantation, and IFN-free therapy with daclatasvir and asunaprevir was started. Although he experienced catheter-related bacteremia on the first day, the IFN-free therapy was safely continued, which immediately caused his liver function to improve. His bilirubin levels decreased from 11.1 to 2.1 mg/dL and serum hepatitis C virus RNA levels became undetectable after 4 weeks of the treatment. This case indicates that IFN-free therapy for progressive SCH with acute cellular rejection and bacterial infection is safe and effective, and may improve the outcomes of hepatitis C virus positive transplant recipients.

BACKGROUND/AIM Contrast-enhanced ultrasonography (US) has improved the detection and characterization of focal hepatic lesions. Recently, the importance of obtaining high-quality samples in the biopsy of hepatic lesions has been increasing not only in the field of pathological diagnosis but also in molecular analysis for predicting the effectiveness of anticancer agents and molecular targeted drugs. We evaluated the utility of Sonazoid-enhanced ultrasonography (SEUS) in guiding percutaneous biopsy of focal hepatic lesions by comparing the results of histopathological diagnosis between B-mode US and SEUS guidance. METHODS AND MATERIALS This retrospective study examined 121 focal hepatic lesions in 108 patients (mean age: 63.8 years) referred for US-guided percutaneous biopsy. The technical success rate was defined as the percentage of the lesions diagnosed clearly at the initial biopsy. RESULTS Among 121 lesions, 56 lesions were subjected to biopsy with B-mode US guidance whereas 65 were subjected to SEUS guidance. The technical success rate was significantly higher under SEUS guidance than under B-mode US guidance (92.3 vs. 76.8%, respectively, P

AIM: Hepatitis B recurrence after liver transplantation can be reduced to less than 10% by combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG). The aim of this study was to evaluate the efficacy and safety of prophylaxis with entecavir (ETV), which has higher efficacy and lower resistance rates than LAM, combined with HBIG in preventing hepatitis B recurrence after living-donor liver transplantation (LDLT). METHODS: Twenty-six patients who received ETV plus HBIG (ETV group) after LDLT for hepatitis B virus (HBV)-related end-stage liver disease were analyzed by comparing with 63 control patients who had received LAM plus HBIG (LAM group). RESULTS: The survival rates of the patients treated with ETV plus HBIG was 73% after both 1 and 3 years, and there was no statistical difference between the patients in the ETV group and LAM group. No HBV recurrence was detected during the median follow-up period of 25.1 months in the ETV group, whereas the HBV recurrence rate was 4% at 3 years and 6% at 5 years in the LAM group. No patients had adverse effects related to ETV administration. CONCLUSION: ETV combined with HBIG provides effective and safe prophylaxis in preventing hepatitis B recurrence after LDLT.

End-stage liver disease associated with hepatitis C virus (HCV) infection is the leading indication for liver transplantation. Hepatitis C virus infection recurrence in the graft is common under immunosuppression, leading to an accelerated rate of graft failure. We report the clinical features of four of our patients: three patients presenting with spontaneous hepatitis C virus clearance after liver transplantation and one presenting with transient disappearance of hepatitis C virus postoperatively. The transitional period from surgery to hepatitis C virus clearance was

Summary Recurrence of primary sclerosing cholangitis after liver transplantation is a challenging issue. Liver pathologies of recurrent primary sclerosing cholangitis after living-donor liver transplantation have not been reported. Here, liver pathologies of explanted grafts and biopsies of 9 patients who underwent retransplantation for recurrent primary sclerosing cholangitis were compared with those of native livers. Recurrence was diagnosed in 13 of 36 patients for primary sclerosing cholangitis post–living-donor liver transplantation, and 9 of them underwent retransplantation. All explanted grafts revealed biliary cirrhosis with sclerosing cholangitis, and 6 patients had additional features of active hepatitis. Liver biopsies showed that 3 had active hepatitis in addition to fibrous cholangitis at recurrence of primary sclerosing cholangitis. Two developed active hepatitis later after the diagnosis of recurrence. In explanted grafts, in addition to extensive hilar lymphoplasmacytic cholangitis, 4 cases showed hilar xanthogranulomatous cholangitis. The latter was not evident in 7 native livers. Ductopenia was extensive in all native livers, although such changes were relatively mild in explanted grafts at retransplantation. Patients with recurrent primary sclerosing cholangitis developed progressive graft failure, and the interval between diagnosis of recurrence and retransplantation (mean, 3.2 years) was shorter than that between diagnosis of primary sclerosing cholangitis and first transplantation (mean, 7.7 years). The rather rapid deterioration of recurrent primary sclerosing cholangitis after liver transplantation may be related to the frequent overlap of active hepatitis.

Background/Aims: To clarify risk factors and clinical features of both hepatitis B surface antigen and anti-HCV negative hepatocellular carcinoma (NBNC-HCC). Methods: HCC patients (n = 1,109) diagnosed at a single center were categorized based on the presence of serum hepatitis B surface antigen and HCVAb. Clinical characteristics of 127 NBNC-HCC patients were evaluated. Results: NBNC-HCC patients were stratified as those with alcoholic liver disease (ALD-HCC, n = 42) and alcohol-unrelated liver disease (non-ALD-HCC, n = 85). Compared with the ALD-HCC group, the non-ALD-HCC group had a higher prevalence of diabetes (p = 0.015), larger tumor size (p = 0.007), and higher tumor marker levels (p = 0.014). Liver function results were significantly worse in ALD-HCC than in non-ALD-HCC. Although the ALD-HCC group had a higher tendency toward recurrence than the non-ALD-HCC group, survival rates were similar between groups (p = 0.352). Conclusion: Alcohol consumption was the most common etiologic factor for NBNC-HCC, and diabetes may be related to the development of HCC in non-ALD-HCC patients. Non-ALD-HCC tended to be diagnosed at a more advanced stage, whereas liver function was worse, and tumor recurrence rate was higher in ALD-HCC patients. Further examination of the risk factors and establishment of a precise surveillance system are necessary for early diagnosis and the development of curative therapies for NBNC-HCC.

Summary. Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n = 17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were −0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Focal granulomatous inflammation developed in the livers of five 10-week-old male Sprague-Dawley rats. The characteristic features of this lesion were the presence of foreign body multinucleated giant cells engulfing calcium deposits and site-specific development in a fissure formed in a sub-lobation in the left lobe or interlobar fissure of the medial lobe of the liver. To clarify the pathogenesis of this lesion, rat livers showing abnormal sub-lobation or lobar atrophy, rat livers in an acute dermal toxicity study and guinea pig livers in a skin sensitization test were also examined histologically. Consequently, the present lesion was considered to be a reactive change against calcium that was dystrophically deposited in the area of hepatocellular necrosis due to delayed circulatory disturbance caused by external pressure or extension force. Granulomatous lesions like in the present cases should be differentiated from those caused by evident exogenous pathogens such as chemicals or microorganisms.

Background. The efficacy of combination therapy with pegylated interferon and ribavirin for recurrent hepatitis C genotype 1 after liver transplantation is limited. In this study, we designed an individualized treatment regimen with pegylated interferon and ribavirin for recurrent hepatitis C based on individual viral responses. Methods. Thirty-four patients with recurrent hepatitis C genotype 1b after living-donor liver transplantation received combination therapy with pegylated interferon α-2b and ribavirin. Treatment was continued for an additional 12 months after serum hepatitis C virus (HCV) RNA became undetectable. Results. Of the 34 patients, 18 became negative for serum HCV RNA within 12 months (range, 1.2-9.9 months; median, 4.0 months). The treatment for the 18 patients was individualized by adding a further 12 months of treatment after the disappearance of serum HCV RNA, resulting in treatment durations of 13.2 to 21.9 months (median, 16.0 months). Notably, 17 (94%) of the 18 patients who received the individualized extended treatment achieved sustained virologic response (SVR), resulting in a 50% SVR rate. Six patients (18%) discontinued the treatment, but none of the 18 patients who received the extended protocol withdrew from the study. Conclusions. Individualized extension of combination therapy with pegylated interferon and ribavirin for recurrent hepatitis C after liver transplantation resulted in a high SVR rate and good tolerability.

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)-positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV-positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti-hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti-hepatitis B core antigen (anti-HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti-HBc-positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV-positive individuals who are positive for anti-HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN-mediated eradication of HCV.

Background De novo activation of HBV occurs after liver transplantation from hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)- positive donors, even under hepatitis B immunoglobulin (HBIG) prophylaxis. One reason for the activation of HBV is the emergence of HBV with escape mutations from hepatitis B surface antibody (anti-HBs). The aim of this study is to clarify the clinical features for de novo activation of HBV with anti-HBs escape mutations after liver transplantation. Methods Clinical features of 75 patients who received HBIG prophylaxis >6 months after liver transplantation with liver grafts from anti-HBc-positive donors were retrospectively analysed. Results Among the 75 recipients, 19 (25%) developed de novo activation of HBV. Of the 19 recipients, the emergence of HBV with anti-HBs escape mutations was confirmed in 7 patients. The rate of de novo activation of HBV with anti-HBs escape mutations was 12% at 5 years. Sequence analysis revealed mutations in the common ‘a’ determinant region of the surface gene, including G145R, G145A and Q129P, in HBsAg. Administration of entecavir immediately after the occurrence of de novo HBV activation resolved hepatitis and induced clearance of serum HBsAg and HBV DNA in all four patients receiving entecavir. Conclusions Escape mutations from anti-HBs caused de novo activation of HBV under HBIG prophylaxis after liver transplantation. Early administration of entecavir was effective on de novo activation of HBV with anti-HBs escape mutations.

Extramedullary plasmacytoma of the liver is rare. Here, we report a case presenting with rupture of extramedullary plasmacytoma of the liver. She had a past history of multiple myeloma with IgA lambda type. Her serum was positive for hepatitis C virus infection and exhibited elevated levels of serum protein induced by vitamin K absence or antagonist-II. She was initially diagnosed as rupture of hepatocellular carcinoma (HCC) and then treated with transarterial chemoembolization (TACE) since bloody ascites and formation of hematoma were seen around hyper-vascular liver tumors on computed tomography. However, the clinical course of this case after TACE was atypical for HCC rupture, as shown by the development of a huge intra-abdominal abscess extending from the liver tumor. Immuno-histochemical analysis of the tumor biopsy specimen revealed massive infiltration of plasma cells expressing IgA and lambda chain. To our knowledge, this is the first case of rupture of extramedullary liver plasmacytoma.

The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients.One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age +/- SD 48.8 +/- 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age +/- SD 46.6 +/- 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR.Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum.A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.

We retrospectively reviewed our 10-year experience with living donor liver transplantation (LDLT) in 30 consecutive patients with end-stage primary sclerosing cholangitis (PSC) to determine long-term patient and graft survival and risk factors for recurrence of PSC. For strict diagnosis of recurrence, patients with hepatic artery thrombosis (n = 2), ABO blood type incompatible transplantation (n = 3), and postoperative survival shorter than 1 year (n = 5) were excluded from the study, leaving 20 patients for analysis. Recurrence was diagnosed in 11 patients 26-71 months after transplantation. Multivariate analysis showed that cytomegalovirus diseases within 3 months after transplantation and related donors were independent risk factors for recurrence. When the effects on recurrence were compared among donor-recipient relationships, there were significant differences, especially between nonrelated donors and parents. Multivariate analysis showed that age was an independent risk factor for time to graft loss. Cytomegalovirus prophylaxis and avoidance of related donors are important in reducing PSC recurrence, although this is a preliminary report with limitations due to the small number of patients. LDLT for young patients with PSC using grafts from their parents might have to be avoided where deceased donor liver transplantation is available.