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Objective: It is a generally accepted fact that eradication of hepatitis virus C inhibits the subsequent development of hepatocellular carcinoma (HCC). On the contrary, a significant population of patients developed HCC despite sustained virological responses (SVRs) to interferon (IFN) therapy. Methods: A total of 415 patients with chronic hepatitis C, who were treated at our hospital between 2004 and 2014, were enrolled for this study. We examined the risk factors for HCC development after IFN therapy. Results: After analyzing various clinical parameters, it was concluded that a serum albumin (ALB) level Conclusions: In patients with a serum ALB level

Background and Aims: Direct-acting antivirals (DAAs) dramatically improve the sustained virological response (SVR) of chronic hepatitis C (CHC) patients. However, continuous liver damage after SVR may be a risk of hepatocellular carcinoma (HCC). We clarified pretreatment characteristics related to sustained liver damage after SVR. Methods: A total of 286 CHC patients were treated with an interferon-free DAA regimen. Among them, 250 patients achieved SVR for 12 weeks after the end of treatment (SVR12); these individuals were classified based on α-fetoprotein (AFP) and alanine transaminase (ALT) levels posttreatment. Baseline characteristics significantly associated with AFP >5 ng/mL and ALT level ≥20 IU/L after SVR were clarified using multivariate analyses. Results: Among the pretreatment factors examined, serum AFP values and the presence of fatty liver (FL) were significantly associated with abnormal AFP (p < 0.0001) and ALT levels 12 weeks after SVR12 (SVR24; p = 0.0109). For 126 patients who showed an increase in baseline AFP level, FL, fibrosis-4 (FIB-4) index, and albumin levels before treatment were related to abnormal AFP at SVR24 (p = 0.0005, 0.0232, and 0.0400 for FL, FIB-4 index, and albumin, respectively). Similarly, for 150 patients with abnormal baseline ALT levels, FL was associated with an ALT level ≥ 30 IU/L after SVR (p = 0.0430). Conclusions: High FIB-4 index, low albumin level, and FL before DAA treatment were associated with a risk of sustained liver damage with AFP and ALT elevation after SVR; patients with these factors should be carefully monitored for emergence of HCC.

Background: Tumors classified based on the Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are heterogeneous in nature. Previously, the Kinki criterion was proposed for a more precise subclassification of tumors in BCLC-stage B. However, tumors in sub-stage B2 include various size and number of HCCs even with the Kinki criteria, which could lead to heterogeneity for overall survival (OS). In this study, we assessed how the size and number of tumors affect the OS and time to progression (TTP) in patients with Kinki criteria stage B2 tumors and treated with transarterial chemoembolization (TACE). Methods: Of 906 HCC patients treated with TACE at Kindai University Hospital, 236 patients with HCC considered as Kinki criteria stage B2 were examined. They were classified into the following 4 groups according to the maximum tumor diameter and number of tumors: B2a group, tumor size ≤6 cm and total number of tumors ≤6; B2b group, size ≤6 cm and number >6; B2c group, size >6 cm and number ≤6; and B2d group, size >6 cm and number >6. The OS and TTP of patients in each group were compared. Results: There were 131 patients (55.5%) in the B2a group, 58 (24.6%) in the B2b group, 41 (17.4%) in the B2c group, and 6 (0.03%) in the B2d group. Comparison of the survivals revealed that the median OS was 2.8 years (95% CI 2.0-3.5) in the B2a group, 2.8 years (95% CI 2.0-3.3) in the B2b group, 1.9 years (95% CI 0.8-4.0) in the B2c group, and 2.3 years (95% CI 1.2-ND [no data]) in the B2d group, respectively (p = 0.896). The median TTP in B2a, B2b, B2c, and B2d sub-substage HCC were13.2, 12.1, 13.8, and 11.5 months, respectively (p = 0.047). The median TTP in B2a + B2c sub-substage patients was longer than that in B2b + B2d sub-substage HCC patients (14.0 months and 10.4 months; p = 0.002). Conclusion: No significant differences were observed in the OS among HCC patients subclassified based on the maximum tumor diameter and tumor number in Kinki criteria stage B2. Consequently, Kinki criteria stage B2 HCC is a homogeneous subgroup in terms of OS prediction. However, shorter TTP in B2b+B2c sub-substage HCC patients than that in B2a + B2c sub-substage HCC patients suggests that different treatment strategy, such as systemic therapy with targeted agents instead of TACE, may be suitable to preserve the liver function.

Objective: Refractory ascites reduces the quality of life of liver cirrhosis patients. Albumin preparation and diuretics, such as furosemide, have been used to treat refractory ascites, but the effect was poor in many patients. In this study, we analyzed patients treated with tolvaptan (TLV) at our hospital and investigated predictors of the effect. Methods: The subjects were 70 patients for whom TLV was introduced to treat refractory ascites who could be analyzed between November 2013 and March 2015 at our hospital. Patient background before initiation of oral TLV treatment, the dose of diuretics, and each item of biochemical tests of blood and urine were investigated, and factors correlated with the treatment effect were analyzed. An increase of ≥1,000 ml in the daily urine volume from the day before oral treatment or a decrease of ≥1 kg in the body weight within 7 days as an early effect was observed in 33 patients and not observed in 37 patients. TLV treatment was continued for 60 days or longer in 12 of the 37 patients in whom no early effect was observed, and the presence or absence of a delayed effect and predictors of the effect were investigated. A decrease in ascites on abdominal CT with improvement of subjective symptoms at 60 days was defined as a delayed effect. Results: When early predictors of the effect were investigated by univariate analysis, serum blood urea nitrogen (BUN) and serum creatinine (Cr) were significantly higher in the non-responder group (BUN: p = 0.03, Cr: p = 0.04), but no factor independently associated with the treatment effect was extracted on multivariate analysis. The delayed effect was noted in 4 (33.3%) of the 12 patients, but no predictor of the effect before treatment was identified. However, reactions, such as an increase in serum Na and reduction of urinary osmotic pressure, were observed early after TLV administration in some patients in whom the delayed effect was observed. Conclusions: The diuretic effect of TLV may decrease in renal hypofunction patients. Since the delayed effect was noted in a specific ratio of patients, continuation of TLV administration is an option even though the early treatment effect is poor unless ascites aggravates or adverse effects develop.

Autoimmune hepatitis (AIH) is a disease that is characterized by the presence of autoantibodies and elevated levels of serum immunoglobulin G (IgG) and hepatic enzymes. Its characteristic findings in the liver include interface hepatitis, infiltration of lymphocytes and plasma cells, and rosette formation, and is treated with immunosuppressive drugs. Autoimmune pancreatitis, a pancreatic disease caused by an autoimmune mechanism, is associated with elevated levels of serum IgG4 and the infiltration of IgG4-positive cells into the pancreatic parenchyma, and it is occasionally accompanied by systemic features. This systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and elevated serum IgG4 levels was recently classified as an IgG4-related disease. A few studies have reported AIH cases with infiltrated IgG4-positive plasma cells in the liver, suggesting the involvement of IgG4 in the pathogenesis of AIH. This feature was called IgG4-associated AIH and only two studies have been published. However, the diagnostic criteria of IgG4-associated AIH has not been defined and the epidemiology and clinical features remain uncertain. The degree of IgG4-positive plasma cell infiltration in the liver was different in each article. The serum IgG4 level was not elevated in one study, whereas it was severely elevated in the other. Corticosteroid therapy normalized liver enzymes in both studies. Further studies are needed to define the epidemiological features or diagnostic criteria.