Explore the vast range of titles available.

BackgroundA nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.MethodsTwo-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys.ResultsIn total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation).ConclusionAlthough the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.

To clarify the efficacy of atezolizumab (ATZ) plus bevacizumab (BEV) as the second-line therapy for patients with unresectable hepatocellular carcinoma (HCC). The subjects were 82 patients with HCC receiving ATZ/BEV, including 33 patients with previous therapies with molecular-targeted agents (MTA). Therapeutic efficacy was evaluated using contrast-enhanced CT according to the mRECIST. The Child-Pugh scores were 5, 6,7 and 8 in 40, 35, 5 and 2 patients, respectively, and the extents of HCC progression were BCLC stage A, B and C in 3, 31 and 48 patients, respectively. Early therapeutic efficacy was evaluated in 67 patients, and percentages of patients achieving CR/PR/SD/PD until 12 weeks were 3.0%/29.9%/49.3%/17.9%, respectively, indicating ORR of 32.8% and DCR of 82.1%, The ORR was higher in MTA-naïve patients (40.5%) than in those after discontinuation of lenvatinib due to PD (7.7%, P = 0.0410), while the DCR was equivalent between both patients (83.3% vs 80.0%, P = 0.1184), and the multivariate analysis revealed previous MTA therapies with lenvatinib alone as a factor to deteriorate the ORR (HR of 4.846 (P = 0.0619)). The OS rates at 24 and 48 weeks were 86% and 72%, respectively, and the rates did not differ between MTA-naïve and MTA-experienced patients. Multivariate analyses revealed that achievement of CR, PR or SD and peripheral neutrophil/lymphocyte ratio were associated with a favorable outcome (HR of 0.124, P<0.0001 and 0.351, P = 0.0303). ATZ/BEV merits consideration even for MTA-experienced patients, since the OS was equivalent to those in MTA-naïve patients despite of an unfavorable early therapeutic efficacy.

BackgroundThis study sought to clarify the factors involved in virologic failure in patients with HCV receiving retreatment with glecaprevir/pibrentasvir (GLE/PIB) in real-world practice.MethodsForty-two patients who had previously received direct-acting antivirals (DAAs) therapies consisting of 35, 3, 3, and 1 patient(s) with genotype (GT)-1b, GT-2a, GT-2b, and GT-3b HCV, respectively, received GLE/PIB for 12 weeks. Resistance-associated substitutions (RASs) at baseline were evaluated, and the dynamics of NS5A-RASs were assessed by deep sequencing in patients showing virologic failure.ResultsBaseline NS5A-RASs were found in all the patients with GT-1b HCV including 16 patients with NS3-RASs. In contrast, both NS5A-RASs and NS3-RASs were absent in 3 and 2 patients with GT-2a and GT-2b HCV, respectively. Virologic failure occurred in 3 patients with GT-1b HCV with NS5A-P32del, while a sustained virologic response (SVR) was achieved in the remaining 39 patients including those with GT-1b HCV carrying NS5A-L31V + Y93H and NS5A-A92K. Virologic failure even occurred in a patient in whom the NS5A-P32del HCV strains had become undetectable by direct sequencing, and the percentage of such strains relative to the total HCV strains was 10%, as determined by deep sequencing. In the other patient with GT-1b HCV with NS5A-P32del, NS3-A156A/V/S were found at 4 weeks after GLE/PIB therapy, but had disappeared at 11 weeks, as determined by direct sequencing.ConclusionsGLE/PIB was effective for patients with HCV who failed to achieve an SVR after prior DAA therapies except in those with GT-1b HCV carrying NS5A-P32del even when such strains became undetectable by direct sequencing.

Oral treatment with asunaprevir and daclatasvir has been reported to yield a SVR ratio of 80% in patients with genotype 1b HCV infection, however, treatment failure has been reported, especially in patients with HCV strains showing the NS5A-Y93H mutation at baseline. An assay system to detect such strains was established to facilitate selection of appropriate candidates for this antiviral therapy. Primer sets and 2 types of cycling probe mixtures were designed, and real-time PCR was performed with HCV-RNA purified from 332 patients with genotype 1b HCV infection, and the results were compared with those obtained by direct sequencing. Both the wild-type and mutant strains were quantified, with a threshold of 4.0 Log copies/mL, in 295 of the 332 patients (88.9%), and the percentage of the mutant strains relative to the total HCV-RNA level in the serum was calculated. The percentage was 0% in 237 patients (80.3%) and 100% in 23 patients (7.8%), identical to the results of direct sequencing. Both wild-type and mutant strains were detected in the remaining 35 patients (11.9%), at levels between 1% and 99%, despite the mutant strains having been undetectable by direct sequencing in 11 patients with percentages of these strains of less than 25%. A novel assay system to quantify the percent RNA of Y93H mutant strains relative to the total HCV-RNA level was established. This system may be useful to determine the indication for treatment with NA5A inhibitors in patients with HCV.

BackgroundThe significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated.MethodsA nationwide survey was performed for patients with ACLF occurring between 2017 and 2019. Cirrhotic patients with a Child–Pugh score of 5–9 were diagnosed as having ACLF when liver failure (serum bilirubin level of ≥ 5.0 mg/dL and a prothrombin time international normalization rate [INR] of ≥ 1.5) occurred within 28 days after an acute insult. Patients who fulfilled either criterion (total serum bilirubin or INR) and/or those with indeterminate Child–Pugh scores at baseline were also enrolled.ResultsAmong the 501 enrolled patients, 183 patients (37%) were diagnosed as having ACLF. The etiologies of the cirrhosis and acute insults were alcohol intake/abuse in 114 (62%) and 75 (41%) patients, respectively. Sixty-eight patients (37%) were also diagnosed as having severe alcoholic hepatitis. The survival rate without liver transplantation was 48% among the ACLF patients and 71% in the remaining patients (P < 0.01). A multivariate analysis revealed that the disease condition was significantly associated with mortality, with an odds ratio of 2.025 in ACLF patients relative to the remaining patients (P < 0.01), and patient age and the number of organs with functional failure were also associated with mortality among the ACLF patients.ConclusionThe proposed diagnostic criteria for ACLF were useful for identifying cirrhotic patients with an unfavorable outcome following acute insults. A therapeutic strategy for patients with severe alcoholic hepatitis should be established, since such patients accounted for the majority of ACLF patients.

This study sought to clarify the usefulness of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC). The subjects were 69 patients with HCC receiving lenvatinib; the median age was 73 years, and 14 and 67 patients had been previously treated with regorafenib and/or sorafenib and therapies without molecular-targeted agents, respectively. Therapeutic efficacy was evaluated using contrast-enhanced CT images obtained 4-8 weeks after the start of lenvatinib and the middle-term outcome using Kaplan-Meier method. The baseline Child-Pugh scores were 5, 6 and 7 in 31, 32 and 6 patients, respectively, and the modified albumin-bilirubin (mALBI) grades were 1, 2a and 2b in 20, 20 and 29 patients, respectively. The Barcelona Clinic Liver Cancer (BCLC) stages following downsizing after prior treatment were A, B and C in 17, 22 and 30 patients, respectively. The therapeutic efficacy was evaluated in 54 patients, and the percentages of patients achieving CR, PR, SD and PD were 3.7%, 44.4%, 37.0%, and 14.8%, respectively. The ALBI scores deteriorated significantly between 4 and 12 weeks after the start of therapy, compared with the baseline. The cumulative survival rates at 48 weeks were significantly higher among patients achieving CR/PR (95.5%) than among those showing no response (54.3%). Multivariate analyses revealed that the BCLC stages and the serum AFP levels were significantly associated with therapeutic efficacy, while the mALBI grade was associated with the middle-term outcome. A favorable middle-term outcome was obtained in patients with HCC receiving lenvatinib, especially in those manifesting grades 1/2a mALBI at baseline, despite the deterioration in ALBI scores during treatment.

To evaluate the long-term efficacy of switching of the nucleos(t)ide analog used for treatment from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in patients with chronic HBV infection. A total of 103 patients with serum HBsAg levels of ≥100 IU/mL who had received ETV were enrolled. The nucleos(t)ide analog used for the treatment was switched from ETV to TAF, and the changes in serum HBsAg levels during the 144-week period before and after the drug switching were compared in 74 patients who had received ETV at least for 192 weeks. Significant decreases of serum HBsAg levels were observed during both the ETV and the TAF administration period, although the degree of reduction was greater during the latter period than during the former period (P<0.001). Significant decreases of serum HBsAg levels were seen in both patients with genotype B HBV infection and genotype C HBV infection, irrespective of the serum HBsAg and HBcrAg levels at the time of the drug switching. Switching of the nucleos(t)ide analog used for treatment from ETV to TAF merits consideration in patients with chronic HBV infection, since the extent of reduction of the serum HBsAg level was greater during the TAF treatment period than during the ETV treatment period.

Background The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection. Methods The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated. Results In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months. Conclusions HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV-DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection.

To establish a therapeutic strategy for cirrhosis patients with gastric variceal bleeding. The outcomes of 137 patients with bleeding gastric varices were evaluated. The bleeding source was gastroesophageal varices (GOV) in 86 patients, and gastric fundal varices (FV) in 51 patients. The Child-Turcotte-Pugh classes were A, B, and C in 26, 79, and 32 patients, respectively; 34 patients (24.8%) had hepatocellular carcinoma (HCC), of which 11 also had complicating portal venous tumor thrombosis (PVTT). Patients with GOV were treated by endoscopic variceal ligation or endoscopic injection sclerotherapy (EIS) with ethanolamine oleate, while those with FV were treated by EIS with cyanoacrylate; 29 patients with FV also underwent additional balloon-occluded retrograde transvenous obliteration (BRTO). Hemostasis was successfully achieved in 136 patients (99.3%), and the cumulative 1-year, 3-year, and 5-year rebleeding rates were 18.1%, 30.8%, and 30.8%, respectively, in the patients with GOV, and 2.2%, 12.5% and 12.5%, respectively, in the patients with FV. The overall 1-year, 3-year, and 5-year survival rates were 79.7%, 71.5% and 64.4%, respectively, in the patients with GOV, and 91.0%, 76.9% and 59.5%, respectively, in the patients with FV. Multivariable analysis identified PVTT and alcoholic cirrhosis as a significant risk factor associated with rebleeding, model for end-stage liver disease (MELD) score and PVTT as significant factors associated with survival. Endoscopic therapies with or without BRTO appeared to be useful therapeutic strategies to prevent rebleeding in patients with gastric variceal bleeding, and favorable outcomes were obtained, except in patients with underlying HCC associated with PVTT and/or severe liver damage.

Aims/Introduction We conducted a 5 year post‐trial monitoring study of our previous randomized 24 week, open‐label, active‐controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction‐associated steatotic liver disease (MASLD), identical to those of pioglitazone. Materials and Methods In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. Results At 5 years, the mean liver‐to‐spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (−4.0%, P = 0.0075 and −7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB‐4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. Conclusions Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years. Ipragliflozin significantly improves MASLD and glycemic parameters, reduces body weight, visceral fat, and fibrosis markers. SGLT2 inhibitors may be a potent therapeutic strategy for the long‐term management of patients with type 2 diabetes complicated by MASLD, given their ability to improve insulin resistance, a key driver of MASLD pathology.