Purpose: To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ + BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC).Method: Ninety-four u-HCC patients who were treated with ATZ + BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ + BV treatment as a first line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n = 46), and patients who received ATZ + BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ + BV was a first line or later line therapy) as the B-IMbrave150-out group (n = 48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. Results:The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ + BV treatment due to fatigue was higher in CP-B than CP-A patients (p = 0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; p = 0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, NLR (hazard ratio (HR), 4.591; p = 0.0160) and B-IMbrave150 criteria (HR,

Aims To assess the safety, efficacy, and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO). Methods A total of 61 highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology. Results The most frequent grade ≥3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child–Pugh grade (CP)‐A and CP‐B, respectively, and 26.7% and 0% in VP4 HCC patients with CP‐A and CP‐B, respectively. Estimated median progression‐free survival and overall survival were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin‐bilirubin grade (hazard ratio 0.372, 95% CI 0.157–0.887; p = 0.0241) and tumor morphology (hazard ratio 0.322, 95% CI 0.116–0.889; p = 0.0287) were independently associated with progression‐free survival in patients with tm50%LO HCC. In VP4 HCC, median progression‐free survival was worse in CP‐B (57 days) than in CP‐A patients (137 days, p = 0.0462). Conclusions Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular‐type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers.

Aims: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. Methods and Results: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). Conclusion: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.

Background Many studies have investigated the prognosis of nonalcoholic fatty liver disease (NAFLD); however, most studies had a relatively short follow-up. To elucidate the long-term outcome of NAFLD, we conducted a retrospective cohort study of patients with biopsy-proven NAFLD. Methods We re-evaluated 6080 patients who underwent liver biopsy from 1975 to 2012 and identified NAFLD patients without other etiologies. With follow-up these patients, we evaluated the outcome-associated factors. Results A total of 223 patients were enrolled, 167 (74.9%) was non-alcoholic steatohepatitis (NASH). The median follow-up was 19.5 (0.5–41.0) years and 4248.3 person-years. The risk of type 2 diabetes mellitus (T2DM) and hypertension was 11.7 (95% confidence interval [CI] 8.70–15.6) and 7.99 (95% CI 6.09–10.5) times higher, respectively, in NAFLD patients than in the general population. Twenty-three patients died, 22 of whom had NASH. Major causes of death were extrahepatic malignancy and cardiovascular disease (21.7%) followed by liver-related mortality (13.0%). All-cause mortality was significantly higher in NASH patients than in nonalcoholic fatty liver patients (P = 0.041). In multivariate analysis, older age (hazard ratio [HR] 1.09 [95% CI 1.05–1.14], P<0.001) and T2DM (HR 2.87 [95% CI 1.12–7.04], P = 0.021) were significantly associated with all-cause mortality. The factors significantly associated with liver-related events were older age, T2DM, milder hepatic steatosis, and advanced liver fibrosis. Body mass index wasn’t associated with either mortality or liver-related events. Conclusions T2DM was highly prevalent in NAFLD patients and was significantly associated with both all-cause mortality and liver-related events. The lean patients’ prognosis wasn’t necessarily better than that of overweight patients.

<b><i>Background:</i></b> We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. <b><i>Methods:</i></b> We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. <b><i>Results:</i></b> Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, <i>p</i> = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; <i>p</i> = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. <b><i>Conclusions:</i></b> The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH.