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Background and Aim: Direct‐acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long‐term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. Methods: This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon‐free DAA treatment before September 2016. The impact of treatment on long‐term hepatic function was followed for at least 4 years after the end of treatment, and the progression to decompensation was evaluated. Results: The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin‐bilirubin (ALBI) grade 2b. During a short‐term follow‐up 1 year after the end of treatment, FIB‐4 index and ALBI score significantly improved. The achievement rates of FIB‐4 < 3.25 (40%) and ALBI grade 1 (70%) reached their plateau in the first year; however, there were significant further improvements in platelet count and α‐fetoprotein level after the first year. The annual incidence of decompensation was 1.30 (95% confidence interval 0.83–2.02) per 100 person‐years. In multivariable analysis, male sex and modified ALBI grade 2b at baseline were associated with decompensation. Conclusions: In a large real‐world cohort of patients with compensated cirrhosis treated with a DAA, remarkable improvement in hepatic function was seen after HCV cure, especially during the first year after the end of treatment. Treatment in the early stage of cirrhosis would be of great benefit for preventing liver deterioration to decompensation. [ABSTRACT FROM AUTHOR]

Background and Aim: Early hepatocellular carcinoma (HCC) recurrence is common, even after achieving hepatitis C virus (HCV) cure. This study was carried out to assess the long‐term trends and predictors of recurrence after HCV cure by direct‐acting antivirals (DAAs). Methods: This retrospective, multicenter cohort study enrolled 365 consecutive patients with chronic hepatitis C who required HCC treatment following sustained viral response (SVR) by DAA administration. Patients with HCC recurrence before SVR were excluded. Late HCC recurrence and its predictors beyond the post‐treatment early phase (24 weeks after SVR) were evaluated. Results: The data of 326 patients were available for the final analysis. The median follow‐up duration from SVR determination was 2.7 years. Median age was 74, and 220 (67.5%) were 70 or over. The corresponding 5‐year cumulative HCC recurrence rates of previous curative and palliative treatment groups were 45.4% and 65.7%, respectively (log‐rank test: P < 0.001). Cox regression multivariable analysis revealed that cirrhosis (hazard ratio [HR] 1.85, P = 0.021), the number of HCC nodules (≥ 2) (HR 1.52, P = 0.031), and previous palliative HCC treatment (HR 1.71, P = 0.012) were independent predictors of late recurrence, in addition to the predictors of early recurrence; AFP > 7 ng/mL at 12 weeks after DAA administration, time from HCC complete response (CR) to DAA initiation (< 1 year), and the number of HCC treatments necessary to achieve CR (≥ 2). Conclusions: The evaluation of fibrosis and characteristics of the previous HCC would allow for better HCC recurrence stratification, which would be helpful for developing long‐term surveillance strategies. [ABSTRACT FROM AUTHOR]

Background and Aim: The addition of hepatitis C virus (HCV) NS3/4A protease inhibitors to pegylated-interferon alpha (PEG-IFNα) and ribavirin (triple therapy) has greatly improved treatment outcome. The aim of this study was to compare the effectiveness and safety of simeprevir-based or telaprevir-based triple therapy for non-cirrhotic patients in real-world clinical practice. Methods: This multicenter study consisted of 835 consecutive Japanese HCV genotype 1b patients treated in a clinical setting, 716 of whom were enrolled (simeprevir = 256 and telaprevir = 460). Logistic regression was carried out after propensity score matching to assess the sustained virological response at week 12 after the end of treatment (SVR12). Results: In the propensity-matched cohort (253 matched pairs), the SVR12 rates of the patients who underwent simeprevir-based or telaprevir-based triple therapy were 85.0% and 84.2%, respectively, by intention-to-treat analysis. Prior treatment response to PEG-IFNa/ribavirin and IL28B genotype was independently associated with SVR12 in both groups. No significant differences in the SVR12 rates stratified by prior treatment response to PEG-IFNα/ribavirin were found between the simeprevir (treatment-naïve 89.1%, prior relapse 94.3%, prior partial response 65.0%, and prior null response 33.3%) and telaprevir (treatment-naïve 87.8%, prior relapse 90.1%, prior partial response 68.4%, and prior null response 50.0%) groups. The incidence of adverse effects, such as anemia, severe rash, and the elevation of serum creatinine, was markedly higher in the telaprevir group. Conclusions: Considering the effectiveness and safety, simeprevir-based triple therapy will continue to be a useful treatment option in Japan for treatment-naïve or prior relapse patients with a favorable IL28B genotype. [ABSTRACT FROM AUTHOR]

Background and Aim The addition of hepatitis C virus ( HCV) NS3/4A protease inhibitors to the pegylated interferon ( PEG-IFN) α and ribavirin combination regimen (triple therapy) has dramatically improved treatment outcome. Unfortunately, anemia remains a common adverse effect. This study was done to compare the development of severe anemia during simeprevir- or telaprevir-based triple therapy. Methods This retrospective multicenter study consisted of 837 consecutive Japanese HCV genotype 1 patients treated in a real-world clinical setting, 811 of whom were enrolled (simeprevir 281, telaprevir 530). The inosine triphosphate pyrophosphatase ( ITPA) genotype at rs1127354 was determined for all studied patients. Logistic regression was done after propensity score matching to assess the risk of development of severe anemia. Results Propensity score matching of the entire study population yielded 266 matched pairs. Severe anemia (nadir hemoglobin < 9.0 g/dL) was developed during the treatment period by 81 (30.5%) and 144 (54.1%) patients treated with simeprevir and telaprevir, respectively. Treatment with simeprevir was independently associated with a lower risk of severe anemia (odds ratio 0.25, 95% confidence interval 0.16-0.38, P < 0.0001). Moreover, ITPA genotype, age, hemoglobin level, and estimated glomerular filtration rate at baseline were also independent factors associated with the development of severe anemia. Conclusions Patients treated with simeprevir-based triple therapy have a lower risk of the development of severe anemia than those treated with telaprevir. Moreover, ITPA genotype and age may be useful for individualizing treatment to reduce the risk of anemia-related adverse effects. [ABSTRACT FROM AUTHOR]

Background and Aim: Thrombocytopenia (TCP) of chronic hepatitis C patients with cirrhosis has a negative impact on the management of interferon-based treatment. The aim of this study is to evaluate the efficacy and safety of telaprevir-based triple therapy for patients who have undergone splenectomy (Spx). Methods: This prospective, multicenter study consisted of 80 patients, including 32 Spx and 48 non-Spx/TCP (platelet count: 60-99 x 109/L) patients with advanced fibrosis infected with hepatitis C virus genotype 1b. All received 12 weeks of telaprevir in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin. Results: The sustained virological response (SVR) rate of the Spx group (75.0%) was significantly higher than that of the non-Spx/TCP group (52.1%) (P < 0.05). Under favorable conditions such as treatment-naïve/prior relapse and interleukin-28B (IL28B) TT allele (rs8099917), the SVR rates of the Spx group were significantly higher than those of the non-Spx/moderate TCP (60-79 x 109/L) groups (91.3% vs 50.0% and 93.8% vs 37.5%, respectively; both P < 0.05). Adequate PEG-IFNα2b adherence was associated with SVR. However, the percentage of patients who achieved 80% adherence to PEG-IFNα2b in the non-Spx/moderate TCP (42.9%) group was significantly lower than that of the Spx (79.3%) and non-Spx/mild TCP (80-99 x 109/L) (80.0%) groups. Treatment discontinuation due to adverse effects and the development of bacterial infection did not differ between the Spx and non-Spx/TCP groups. Conclusion: The increase of platelet count after Spx contributed to treatment success, especially for moderate to severe TCP patients who are treatment-naïve/prior relapse or IL28B TT allele. [ABSTRACT FROM AUTHOR]

Background and Aims: Pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN α-2b and RBV treatment due to adverse effects in patients with chronic HCV infection. Methods: A total of 2871 Japanese patients who had chronic HCV infection treated with PEG-IFN α-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation. Results: Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms ( n = 77, 30.8%), depression-related syndrome ( n = 46, 18.4%), hematologic effects ( n = 41, 16.4%) and dermatologic effects ( n = 27, 10.8%). The rate of discontinuation of treatment for patients aged ≥ 65 years was significantly higher than for patients aged < 65 years, for both men ( P < 0.0001) and women ( P = 0.0121). Moreover, the frequency of discontinuation due to neurovegetative symptoms, depression-related syndrome, and hematologic effects for men aged ≥ 65 years was significantly higher than for those aged < 65 years ( P = 0.0001, P = 0.0016, and P = 0.0170, respectively), but not for women. Conclusion: Premature discontinuation due to the adverse effects of PEG-IFN α-2b and RBV treatment by patients with chronic HCV infection is mainly due to neuropsychiatric symptoms and is more common for older than for younger patients. [ABSTRACT FROM AUTHOR]

Editorial. Discusses staging systems for hepatocellular carcinoma. Child-Pugh score; Okuda Classication; Tumor node metastasis staging; Des-gamma-carboxyl prothrombin.

The age distribution of patients with hepatocellular carcinoma (HCC) now peaks at nearly 70 years in Japan and this is continually increasing. Whether such elderly patients with HCC aged 80 years or older should be treated, and if so, how they should be selected for treatment remains uncertain. The present study was undertaken to determine any differences in the clinical characteristics and prognostic features between patients with HCC aged 80 years or older and those younger than 80 years of age. We also aimed to identify any significant variables in the prognosis of elderly patients with HCC aged 80 years or older. Seven hundred and four patients with HCC, diagnosed during a 12-year period from January 1989 to December 2000, were categorized into two groups as follows: (i) 36 patients aged 80 years or older at the detection of HCC were defined as the elderly group and; (ii) 668 patients younger than 80 years of age were placed in the non-elderly group. Clinical variables were analyzed and compared between the two groups, and any significant variables in the prognosis were simultaneously determined. Regarding sex, viral markers, concentration of serum alpha-fetoprotein, diameter and number of tumors, Child's grade, presence of portal thrombosis, histology grade of HCC and any types of treatment, no significant difference was found between the two groups. The 1-year and 3-year survival rates in the elderly group (54.1 and 28.1%, respectively) were not significantly different from those in the non-elderly group (69.9 and 43.2%, respectively; P = 0.1053). The only significant factor in the prognosis in the elderly group was the presence of portal thrombosis, although a Child's grade of B or C was almost a significant factor with a P-value of 0.063. Tumor size measuring more than 3 cm in the greatest dimension, non-solitary tumor, Child's grade of B or C, and the presence of portal thrombosis were all found to be prognostic factors in the non-elderly group using a multivariate analysis. An advanced stage of HCC, not advanced age, influenced the survival rate in these elderly patients. Therefore, an optimal treatment strategy should be applied for elderly patients with HCC who demonstrate less prognostic factors in the same manner as that for non-elderly patients. © 2004 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

Abstract Aim: There is a limited amount of data regarding the gender difference in the survival in cases of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the difference in the survival between males and females with HCC and the possible factors affecting the gender difference of survival in HCC. Methods: Analyses were performed based on 704 consecutive patients with HCC observed for 12 years between January 1989 and December 2000 at the Internal Medicine Department, Saga Prefectural Hospital Koseikan, who were retrospectively enrolled in the study. The 1-, 3-, 5- and 7-year survivals and various factors at the detection of HCC were compared between 487 male and 217 female patients with HCC using the Kaplan-Meier method, Mantel-Cox test, chi squared test and Fisher's exact analysis. Results: There was a significant difference in survival between male and female patients with a 1-, 3-, 5- and 7-year survival estimate of 67.7, 40.6, 23.8 and 8.7%versus 73.5, 50.3, 26.3 and 15.4%, respectively (P -value: 0.0167). Of the clinical variables examined, the significant factors related to gender difference were found to be age, tumor size, the number of tumors, the presence of portal thrombosis and the type of follow-up. Of the patients with HCC lesions measuring 3 cm or less in the greatest dimension or those with solitary HCCs, however, there was no significant difference in survival between both sexes. The patients were divided into three categories: closely followed-up group (regular periodic follow-up with monthly alpha-fetoprotein measurements plus ultrasonography at least every 4 months); a non-closely followed-up group; and an incidental group (incidentally discovered due to related symptoms). The detection rates of HCC through the closely followed-up, non-closely followed-up and incidental groups were 19.3%, 46.2% and 34.5% in men and 28.1%, 46.5% and 25.4% in women, respectively, which reached a significant difference between... [ABSTRACT FROM AUTHOR]

Comments on the diagnosis of primary biliary cirrhosis and pernicious anemia. Presence of specific autoantibodies against mitochondria; Categories of chronic atrophic gastritis; Concept of molecular mimicry.