Search

Aim: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. Methods: This was a multicenter, single‐blinded, randomized controlled study (UMIN000007267). Early‐stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non‐HAIC group). The primary end‐point was recurrence‐free survival. Efficacy analysis and safety analysis followed the intention‐to‐treat principle. Results: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non‐HAIC group (n = 35). Recurrence‐free survival rates at 1 (3) year in the HAIC group and non‐HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320–1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child–Pugh score 5. Intrahepatic distant recurrence‐free survival rate in the HAIC group was significantly better than that in the non‐HAIC group (HR, 0.468; 95% CI, 0.235–0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) – grade 2 cholecystitis and grade 2 hyperkalemia. Conclusions: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early‐stage HCC. However, it might be effective in preventing intrahepatic distant recurrence. [ABSTRACT FROM AUTHOR]

Background and Aim It remains unclear whether primary biliary cholangitis (PBC) represents a risk factor for secondary osteoporosis. Methods A case-control study was conducted to examine bone mineral density and bone turnover markers in middle-aged postmenopausal PBC patients without liver cirrhosis. We compared the incidence of low bone mineral density between propensity-score matched subgroups of PBC patients and healthy controls and investigated the mechanisms underlying unbalanced bone turnover in terms of the associations between bone turnover markers and PBC-specific histological findings. Result Our analysis included 128 consecutive PBC patients, all postmenopausal women aged in their 50s or 60s, without liver cirrhosis or fragility fracture at the time of PBC diagnosis. The prevalence of osteoporosis was significantly higher in the PBC group than in the control group (26% vs 10%, P = 0.015, the Fisher exact probability test). In most PBC patients (95%), the level of bone-specific alkaline phosphatase was above the normal range, indicating increased bone formation. On the other hand, the urine type I collagen-cross-linked N-telopeptide showed variable levels among our PBC patients, indicating unbalanced bone resorption. Advanced fibrosis was associated with low bone turnover. Lobular cholestasis, evaluated as aberrant keratin 7 expression in hepatocytes, showed significant negative correlations with bone formation and resorption, indicating low bone turnover. Conclusion Our results show that, compared with healthy controls, even non-cirrhotic PBC patients have significantly higher risk of osteoporosis. Moreover, lobular cholestasis was associated with low bone turnover, suggesting this feature of PBC may itself cause secondary osteoporosis in PBC patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Recent routine testing for anti-mitochondrial antibodies has increased the number of patients with early primary biliary cirrhosis (PBC). The prevalence and clinical significance of esophageal varices in those patients remains obscure. Methods: A systematic cohort analysis of 256 PBC patients was performed to clarify the prevalence, characteristics, and prognosis of the patients with early PBC and esophageal varices. Results: Twenty-two patients had esophageal varices at the time of diagnosis: 5.5% (12/217) with early disease of histological stage 1 or 2, and 25.6% (10/39) with advanced disease of stage 3 or 4. Immediate treatments were required for two patients with early PBC: one for bleeding varices, and the other for large varices. The overall survival of the patients with early PBC and esophageal varices at diagnosis did not significantly differ from that of patients without esophageal varices ( P = 0.66). High alkaline phosphatase (ALP) ratios (odds ratio = 2.3) and low platelet counts (odds ratio = 0.77) were significantly associated with the presence of esophageal varices in the patients with early PBC. Significant associations of these two factors with the development of esophageal varices during follow-up were also revealed (odds ratio = 1.4 and 0.88, respectively). The patients with early PBC and high ALP ratios ≥ 1.9 had significantly high risks of developing esophageal varices during follow-up ( P = 0.022). Conclusions: High ALP ratios and low platelet counts at diagnosis and decreased platelet counts during follow-up are useful predictors of esophageal varices in patients with early PBC. [ABSTRACT FROM AUTHOR]

Background and Aims: It still remains controversial whether gastric mucosal atrophy and intestinal metaplasia are reversible after eradication of Helicobacter pylori infection. The aims of this study were to evaluate the histological changes in gastric mucosa after H. pylori eradication during long-term follow-up periods, and to verify the propriety of H. pylori eradication for the elderly population. Methods: Two hundred and forty-one patients with H. pylori infection and 84 cases more than 60 years old were classified as the elderly group. The mean follow-up period was 101 months. A series of endoscopic examinations with five-point biopsies were performed before and every year after H. pylori eradication. We evaluated the histological grades according to the Updated Sydney System. Statistical analysis was performed using the Wilcoxon signed rank test and the Mann–Whitney U-test, and P < 0.05 was considered to be statistically significant. Results: The atrophic grades improved only at the angle in the 5th year and at all points, except for the antrum, in the 10th year after H. pylori eradication. In the elderly group, the atrophic score improved in both the 5th and 10th year. However, improvement in the younger group was achieved only in the 10th year. The metaplastic score did not change in either the 5th or 10th year after H. pylori eradication in all patients. Conclusion: Eradication of H. pylori infection improved gastric atrophy and prevented the progression of intestinal metaplasia in the elderly population during the long-term follow-up periods. H. pylori eradication for the elderly population is effective. [ABSTRACT FROM AUTHOR]

Aim: The peak age of the presentation of autoimmune hepatitis (AIH) is between 40 years and 50 years. Elderly patients have been reported to have higher frequencies of concurrent thyroid or rheumatic diseases and histological cirrhosis and a lower occurrence of treatment failure. In this study, we assessed the clinical features of Japanese type 1 AIH in adolescence and early adulthood. Methods: Fifteen patients aged ≤ 30 years (group 1) were compared with 79 patients aged between 40 years and 50 years (group 2). Results: At presentation, patients aged ≤ 30 years accounted for 9% of the study population. Although frequencies of extrahepatic concurrent autoimmune diseases were similar between groups 1 and 2, a tendency toward a lower frequency of concurrent autoimmune thyroiditis was shown in group 1 (0 vs. 18%, P = 0.08). Group 1 had a lower frequency of human leukocyte antigen DR4 (27 vs. 78%, P = 0.002), and histological acute hepatitis was shown more frequently in group 1 (27 vs. 4%, P = 0.002). However, there were no differences in frequencies of the normalization of serum transaminase levels after the introduction of corticosteroid treatment or relapse after the normalization of serum transaminase levels between the two groups. Conclusions: Japanese type 1 AIH patients in adolescence and early adulthood respond well to corticosteroid treatment. However, they may frequently show atypical features, and the diagnosis of type 1 AIH in adolescence and early adulthood may be difficult and should be made carefully. [ABSTRACT FROM AUTHOR]

Background/Aims: Adherence to combination therapy with interferon (IFN) or pegylated IFN plus ribavirin for chronic hepatitis C patients is important for a better virological response. However, the impact of the patient's treatment experience and treatment centre on adherence to combination therapy has not been fully analysed. In this prospective study, we analysed the factors that might have an effect on adherence to therapy in patients who had initial or retreatment IFN therapy. Patients and methods: We consecutively enrolled 363 patients with chronic hepatitis C; 221 were IFN naïve and 142 were undergoing retreatment. The mean ages of the naïve and retreatment groups were 54.8 and 55.7 years respectively. IFN α-2b was administered daily for 2 weeks, followed by three times per week for 22 weeks, while ribavirin was administered daily. We evaluated the tolerability and response to combination therapy and analysed its relevant factors. Results: Of the 363 patients, 189 (52%) achieved 80% adherence. The multivariate logistic regression analysis revealed that retreatment, centre with more patients treated, patient age (<55 years), male, genotype 2 and dosage of IFN per weight (<0.13 million units/kg) were associated with achievement of 80% adherence to combination therapy. Accordingly, the achievement of 80% adherence was more frequent in the retreatment (62%) than that in the naïve group (46%) ( P<0.01) and in centres with more patients treated (57%) than in those with less patients treated (46%) ( P=0.03). Conclusion: The present data suggest that the patient's motivation and the physician's treatment experience may be important for a better adherence to combination therapy for patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Aim: Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients. Methods: A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique. Results: Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (≥ 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups. Conclusions: ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful. [ABSTRACT FROM AUTHOR]

Aim: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. Methods: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non-receiving PSE patients (non-PSE group). Results: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7–21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non-PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non-PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non-PSE group reduced the dose of pegylated IFN-α-2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non-PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. Conclusion: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background and Aims: A prospective , non-randomized cohort study on long-term lamivudine treatment , comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)–related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV-DNA > 5 log10 copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. Results: Lamivudine reduced HBV-DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV-DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. Conclusions: Lamivudine was effective in reducing HBV-DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation. Methods: We investigated the prognostic factors associated with 1-week fatal outcomes after the diagnosis of fulminant hepatic failure, which were associated with fatal outcomes prior to receiving liver transplantation, in 104 patients with non-acetaminophen-related fulminant hepatic failure. Results: With a multivariate logistic regression analysis, age (>40 years), systemic inflammatory response syndrome (SIRS) and plasma prothrombin activities (≤10%) were significantly associated with fatal outcomes at 1 week after diagnosis in 104 patients. At the time of diagnosis, 50 patients (48%) were in a state of SIRS. Significant differences were observed between patients with and without SIRS regarding the period from the initial symptoms to the diagnosis of fulminant hepatic failure, hepatic coma grade, serum alanine aminotransferase level, serum creatinine level and plasma prothrombin activity. With a multivariate logistic regression analysis, age (>40 years), cause of fulminant hepatic failure (viral hepatitis), plasma prothrombin activity (≤10%) and no administration of protease inhibitor were significantly associated with the 1-week fatal outcomes of 50 patients with SIRS. Conclusions: Patients with SIRS exhibited hepatic failure of increased severity and SIRS may reduce the probability of receiving a liver transplantation. In order to estimate the efficacy of protease inhibitor for patients with SIRS, a prospective randomized trial is required. [ABSTRACT FROM AUTHOR]

Background: Although a variety of papers demonstrated inhibited hepatocarcinogenesis with interferon (IFN) therapy for chronic hepatitis C, a small number of hepatocellular carcinomas (HCC5) were still observed even in sustained virologic responders. Aims: To clarify factors affecting the development of HCC, we analyzed the frequency of HCC in sustained virologic responders over a long-term observation period. Methods: Seven hundred and ninety-two out of the 2623 IFN-treated hepatitis C patients who had undergone liver biopsy showed sustained virologic response. Screening for development of HCC was performed periodically during an average follow-up of 5.1 years. Fibrosis of the pretreatment liver biopsy sample was graded. Risk factors for HCC were analyzed by using Cox proportional hazards regression. Results: Of 792 patients, 23 developed HCC. Univariate analysis showed that stage of hepatic fibrosis, age, and alcohol consumption were significantly associated with a risk of HCC (P< 0.00 1). There was a significant difference in the cumulative incidence between patients stratified according to these variables (P< 0.00 1). Conclusions: Pretreatment hepatic fibrosis score, age, and alcohol consumption may affect development of HCC even in sustained virologic responders. Thus, patients with these factors should be carefully followed even after eradication of the virus. [ABSTRACT FROM AUTHOR]

To elucidate the positive frequency of hepatitis B virus (HBV) DNA in patients with hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (HCVAb) negative (NBNC) chronic liver disease, we detected serum HBV-DNA using the real-time detection polymerase chain reaction method (RTD-PCR) in comparison with HBsAg and HCVAb negative individuals with normal alanine aminotransferase (ALT). We also revealed the nucleotide sequence of the X-pre-C gene-coding region of intrahepatic HBV-DNA. Serum HBV-DNA was detected in 12 of 36 NBNC patients (five of 22 chronic hepatitis, three of eight liver cirrhosis and four of six hepatocellular carcinoma), whereas none of 31 control individuals were positive for serum HBV-DNA (P<0.01). Serum antibody to hepatitis B core antigen (HBcAb) was positive in nine of 36 in patients with NBNC patients and was positive in nine of 31 in control individuals (n.s). Five of six NBNC patients with serum HBV-DNA positive by RTD-PCR were also positive for intrahepatic HBV-DNA. Analysis of the nucleotide sequence of the X-pre-C coding region of HBV-DNA in the liver showed similar mutation sites of 1677, 1679, 1709, 1753, 1762, 1764. These findings suggested that serum HBV-DNA was more frequently detected in NBNC patients than normal individuals and the presence of low levels of serum HBV-DNA was correlated to the 1677–1764 X-pre-C mutations. [ABSTRACT FROM AUTHOR]