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We investigated pretreatment neutrophil-to-lymphocyte ratio (NLR) for predicting survival outcomes of atezolizumab plus bevacizumab therapy for hepatocellular carcinoma (HCC) and determined the predictive ability of combined liver reserve-NLR.This retrospective, multicenter study enrolled 242 patients receiving atezolizumab plus bevacizumab for unresectable HCC. Pretreatment NLR2.56 was designated as the "low group" and NLR ≥2.56 as the "high group" (120 and 122 patients, respectively). Propensity score-matched analysis was undertaken between the low and high groups.In this cohort, the objective response and disease control rates were 20% and 72.5%, respectively, in the low group and 19.6% and 72.9%, respectively, in the high group. After matching, median progression-free survival (PFS) time was 283 and 167 days in the low and high groups, respectively (p = 0.022). Neutrophil-to-lymphocyte ratio ≥2.56 (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.05-2.28; p = 0.028), modified albumin-bilirubin index (mALBI) grade 2b or 3 (HR 1.55; 95% CI, 1.05-2.29; p = 0.025), and protein induced by vitamin K absence or antagonist-II ≥ 400 (HR 2.03; 95% CI, 1.36-3.02; p = 0.001) were significantly associated with PFS in univariate analysis using the Cox proportional hazards model. In cases involving mALBI grade 1 or 2a (n = 131), the median PFS time was not reached in the low group, whereas it was 210 days in the high group (p = 0.037).Pretreatment NLR is a simple tool for routine measurement in clinical practice. It can predict PFS in patients with unresectable HCC treated with atezolizumab plus bevacizumab, especially mALBI grade 1 or 2a.

We herein report a 68-year-old man who underwent nephrectomy for right renal cell carcinoma 10 years prior. He remained under regular medical observation, and abdominal computed tomography showed tumors in the head and tail of the pancreas. He was diagnosed with pancreatic metastasis from renal cell carcinoma. He underwent surgical excision. The pathologic diagnosis proved that the pancreatic tumors were metastases from renal cell carcinoma and clarified that an ectopic pancreas in the duodenum had metastases as well. To our knowledge, this is the first case of metastasis to an ectopic pancreas.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

Background A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. How to cite this article Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78-83.

AIM The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naive patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P

We experienced a rare case of acute pancreatitis caused by Candida infection. A 52-year-old man was admitted to our hospital with a chief complaint of abdominal pain. Blood tests revealed high amylase and hepatobiliary enzyme abnormalities, and the patient was hospitalized for acute pancreatitis. Abdominal computed tomography showed a 15-mm space-occupying lesion at the parenchyma of the pancreatic head. Endoscopic retrograde cholangiopancreatography was performed after conservative treatment, which revealed a cystic lesion with a suspected solid component inside involving both lower bile duct and pancreatic duct. Cytology of collected bile and pancreatic juice revealed innumerous hyphae and spores morphologically consistent with Candida spp., as did endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor site. Empiric therapy with oral fluconazole resulted in reduction of the space-occupying lesion 3 months after discharge. However, acute pancreatitis recurred about 1 year and 6 months after discharge. After conservative treatment was carried out again, the same lesion was fenestrated by endoscopic sphincteroplasty, and its internal solid components were resected using a basket catheter. Pathological analysis confirmed the presence of fungus balls and degenerated substances. Candida Albicans was identified by fungal culture examination. After the excretion of the fungus balls, pancreatitis did not recur thereafter during outpatient follow-up.

Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Entecavir is one of the most-used nucleoside analogues for the treatment of patients with chronic hepatitis B virus (HBV) infection. The aim of this study was to clarify the effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma (HCC). The participants were 249 patients with chronic HBV infection who had been treated by entecavir for more than 2 years. Hepatic functional reserve and incidence of HCC were evaluated, and the factors that might contribute to the development of HCC were analyzed. Prothrombin activity was significantly elevated at 60 months after starting entecavir (from 85.9 ± 17.4 to 97.0 ± 16.9 %, p

Aim To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice. Methods Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated. Results Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect. Conclusion Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.

We report the use of balloon-occluded retrograde transvenous obliteration (BRTO) for portosystemic shunt in one patient, resulting in marked improvements in residual liver function and enabling safe hepatitis C virus (HCV) elimination with direct-acting antiviral agents. A woman undergoing outpatient treatment at our institution for HCV-related cirrhosis with a history of hepatocellular carcinoma (HCC) treatment developed hepatic encephalopathy (HE; Child-Pugh score 8) at age 65 years. Improvement was obtained with conservative treatment; however, contrast-enhanced computed tomography revealed a splenorenal shunt with decreased portal vein blood flow. Therefore, BRTO was performed to prevent HE recurrence, to improve liver function, and to enable administration of direct-acting antivirals. Postoperatively, marked reduction of the shunt flow was confirmed, and the Child-Pugh score improved from 8 to 5. Subsequent recurrence of HCC was treated with local therapy, after which combination therapy with asunaprevir and daclatasvir was performed, achieving sustained virologic response 24 weeks after completion. No subsequent recurrence of HCC or HE has been observed to date. Copyright © 2017 John Wiley & Sons, Ltd.

症例は25歳 女性．ダウン症候群と診断され，幼少期に心室中隔欠損症術を受けた際に輸血あり．20歳時にC型肝炎ウイルス（HCV）の感染を指摘された．肝機能異常あり，HCV genotype 2a，ウイルス量3.2 logIU/ml であった．インターフェロン適応ありと判断し，ペグインターフェロンα-2aを投与した．しかし白血球減少症を来し，以後インターフェロンβに切り替え投与した．その後合併症なく治療を完遂し，HCV-RNA陰性化およびトランスアミナーゼ正常化が得られた．ダウン症候群合併C型肝炎では，インターフェロンによるウイルス学的著効が得られる症例は稀とされている．また精神的な副作用を予測し難いため，治療をためらう事例も多い．しかし近年，ダウン症候群の余命は延長し，C型肝炎合併例では肝炎が予後を左右する場合もある．本症例は，ウイルス側および宿主側に著効し易い素因を持ち，かつインターフェロンβによる治療完遂が可能であった．この様な症例では積極的な抗ウイルス療法を考慮する必要がある．

A nationwide survey of autoimmune hepatitis (AIH) was conducted in Japan, and the clinical features of patients with AIH were analyzed. A total of 1,056 patients were enrolled through questionnaires sent to 153 hospitals and clinics with hepatology specialists. The clinical features of Japanese AIH were as follows: (1) most patients were middle-aged women, with ages peaking in the 60s; (2) serum immunoglobulin G (IgG) levels were high, but more than 30% of the patients had serum IgG levels less than 2,000 mg/dl; the cutoff level of IgG to distinguish between patients with AIH and those with chronic hepatitis resulting from hepatitis virus was approximately 2,000 mg/dl; (3) autoantibodies, particularly the antinuclear antibody, were frequently present; (4) most patients showed histological features of chronic hepatitis or liver cirrhosis, but 10.9% of the patients showed histological features of acute hepatitis; (5) approximately 75% of the patients were treated with corticosteroids and showed a favorable response to treatment, whereas ursodeoxycholic acid was administered to 60% of the patients. The clinical features of patients with AIH in Japan were clarified. The mean age at diagnosis was higher than that in previous studies. In addition, the number of patients with AIH having the histological features of acute hepatitis increased. Diagnosis of AIH does not preclude the presence of acute hepatitis and/or serum IgG levels less than 2,000 mg/dl.

We report a patient who developed ulcerative colitis during the course of primary biliary cirrhosis (PBC). PBC was diagnosed by liver histology when the patient was 31 years old, at which time no symptoms were observed. At 45 years of age, the patient complained of bloody diarrhea and abdominal pain, and she was diagnosed with ulcerative colitis by colonoscopy and histological examination. The patient had HLA-DRB1(*)1502 and (*)0802, which are associated with both diseases. Ulcerative colitis should be considered in the differential diagnosis of bowel disease in patients with PBC. The possible genetic associations between 2 diseases are also discussed.

AIM The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. RESULTS The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower (P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher (P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 +/- 103 in F1, 483 +/- 122 in F2, 487 +/- 111 in F3 and 423 +/- 94 in F4). CONCLUSION A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage.

Aim: The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). Methods: We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child–Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed. Results: Subjects with results over the cut-off value for healthy subjects ranged from 11.1–28.6% in CH and 19.5–36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child–Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group. Conclusion: The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients.

症例は56歳男性. アルコール性肝硬変. 平成15年8月より全身倦怠感を自覚. 同年10月より体重増加. 11月8日より39度台の発熱が出現し, 近医入院. 同14日当科入院. WBC 7700/μl, Hb 8.8g/dl, Plt 5.2万/μl, PT 46.1%, T-Bil 4.8mg/dl, AST 129IU/l, ALT 59IU/l, γ;-GTP 27IU/l, Alb 2.5g/dl, 入院当初より左腰背部痛を軽度自覚. 入院後, 肝不全に対して保存的に加療を行ったが, 貧血が進行した. 下血はなく, 上部消化管内視鏡では明らかな出血はなかった. 第6病日, 腹部造影CTにて左腸腰筋の軽度腫大が描出された. 再検前にショックに陥り第7病日死亡. 剖検にて左腸腰筋血腫と診断された. 肝硬変に合併した特発性腸腰筋血腫は稀であるが, 貧血が進行する肝硬変患者における鑑別として重要である.

To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice.Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated.Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect.Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.

The Wilms’ tumor 1 (WT1) gene is known to be overexpressed in hepatocellular carcinoma (HCC) and to upregulate tumor growth and oncogenic potential, although the detailed mechanisms remain to be elucidated. We identified host genes involved in WT1 gene modulation of human liver cancer cell lines in vitro, and further characterized genes related to apoptosis. Moreover, we evaluated the alteration of genes by WT1 in 40 HCC and 58 non-HCC human liver samples collected at resection. Analysis of the effect of small interfering RNAs-mediated knock-down of WT1 on apoptosis using an annexin V labeling assay, and on modulation of the activity of caspases-3, -8 and -9, indicated that WT1 has an anti-apoptotic role. We identified three apoptosis-related genes that were modulated by WT1; the cellular FLICE-inhibitory proteins (cFLIP) gene was upregulated, and Fas-associated death domain (FADD) and nuclear factor kappa B (NF-κB) were downregulated. Interestingly, knock-down of FADD or NF-κB resulted in the upregulation of WT1, and the expression of cFLIP changed in parallel with WT1 expression. We further evaluated WT1-mediated alteration of genes in HCC and non-HCC human liver samples. Both HCC and non-HCC tissues that expressed relatively high levels of WT1 showed cFLIP overexpression. WT1 modulates cFLIP, FADD and NF-κB, and has an anti-apoptotic role in HCC. This mechanism of action of WT1 could be related to the tumor growth and oncogenic potential of HCC.

Background The manner in which ribavirin (RBV) enhances the antiviral effects of interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro. Methods We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from patients with HCV infection who were receiving IFN-α therapy with or without RBV. We added RBV and/or IFN-α to a plasmid-based HCV replication system containing a full-length HCV genotype 1a sequence in HepG2 and Huh7 cell lines and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of ISGs and autocrine IFN-β. Results The expression of protein kinase R and myxovirus resistance A mRNA was enhanced more with IFN-α and RBV than by IFN-α alone in assays in vivo and in vitro. Such enhancement depended on autocrine IFN-β being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in the absence of IFN-α. The IL-8 upregulation induced by RBV was responsible for the activation of activator protein 1 (AP-1). Conclusions Ribavirin augments the anti-HCV effects of IFN-α induced by ISGs through enhancing autocrine IFN-β. Moreover, RBV can enhance IL-8 through activating AP-1. Improved understanding of ISG modulation by RBV would help to establish a means of eliminating HCV.

It is controversial whether steroid therapy should be continued to prevent the recurrence of autoimmune hepatitis (AIH) in patients who have undergone liver transplantation (LTx) due to AIH. We report a case of recurrent autoimmune hepatitis after LTx despite a persistently normal range of alanine aminotransferase (ALT). A 50-year-old woman was admitted to our hospital because of jaundice and severe liver dysfunction, where she was diagnosed with liver failure due to AIH. Steroid therapy was not effective enough and the patient received living-donor LTx in 1999. Following the operation, the level of ALT was maintained within a normal range and anti-nuclear antibody (ANA) became negative, however, the serum level of IgG gradually elevated and ANA became positive, while platelets decreased. A liver biopsy performed 6 years after LTx showed histological findings of AIH and she was diagnosed with recurrent AIH. A recurrence of AIH may occur after LTx even if the level of ALT remains within a normal range. We consider that a protocol liver biopsy should be performed in patients who undergo LTx due to AIH to decide the indication for steroid therapy.

Developing a peptide-based vaccine for the highly variable hepatitis C virus (HCV) remains a challenging task. Variant viruses not only escape antigen presentation but also persist in a patient as quasi-species. Such variants are often antagonistic to the responding T cell repertoire. To overcome these problems, we herein propose a cocktail vaccine consisting of a few epitope peptides, which make it possible to outpace the emergence of variant viruses. To design such a vaccine, we developed a way to identify HLA-A*2402-binding peptides efficiently by means of the computational scanning of the whole genome of the pathogen. Most of the predicted peptides exhibited strong binding to the HLA-A*2402 molecule, while also inducing CD8 T cell responses from the patients’ peripheral blood mononuclear cells (PBMCs). Peptide-induced T cells were capable of lysing HCV-expressing HepG2 cells which process antigens endogenously. The amount of HCV core antigen in the patients’ livers suggested that the lytic activity of the peptide-induced T cells was clearly in a range suitable for therapeutic use. If T cells were activated under optimal conditions by high density peptides, then they tended to be relatively tolerant of single amino acid variations for cytolysis. Finally, an analysis of the viral population isolated in Japan suggested no obvious changes due to immune evasion in the viral genome even in a host population highly biased toward HLA-A*2402.

A 12-year-old girl with Gianotti-Crosti syndrome caused by hepatitis B virus (HBV) infection was admitted due to eruption on her extremities. Laboratory findings revealed elevation of transaminase, positivity for HB surface antigen (HBsAg), and an IgM type anti-HB core. The eruption and level of transaminase improved, and HBsAg became negative within 2 months of onset. Analysis of the virus revealed it to be genotype D with a genomic length of 3,182 bases and the HBsAg serotype was ayw3, which is very rare in Japan. The possible relationship between Gianotti-Crosti syndrome and HBV genotype D infection is discussed.