[Liver injury in patients with moderate II COVID-19 who received dexamethasone monotherapy].

We examined 171 patients with novel coronavirus disease 2019 (COVID-19) with liver injury in the respiratory failure groups and the nonrespiratory failure groups and investigated 41 patients with moderate II COVID-19 with respiratory failure who received dexamethasone (Dex) monotherapy in the liver injury group and the nonliver injury group at the time before treatment. The respiratory failure group had 64% more liver damage than the nonrespiratory failure group, was older, had more men, and had significantly more complications from lifestyle-related diseases such as hypertension and diabetes. Obesity was more common in the liver injury group prior to Dex monotherapy, and the liver CT value was significantly lower than in the nonliver injury group. Liver injury worsened in 41% of patients after Dex monotherapy, but there was no significant difference in the frequency before Dex monotherapy between the liver injury group and the nonliver injury group, and the degree of liver injury was mild in all cases, improving in 38% of the liver injury group. Dex monotherapy was a safe treatment for moderate II COVID-19, which frequently resulted in liver injury.

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study.

AIM: Atezolizumab plus bevacizumab (atezo + bev) shows a good overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients. However, the OS of patients with nonviral infection is quite worse than that in those with viral infection. The present study investigated the efficacy and safety of lenvatinib in patients with nonviral infection, who were unlikely to obtain benefit from atezo + bev. METHODS: We conducted a multicenter retrospective study that included 139 advanced HCC patients treated with lenvatinib between March 2018 and September 2020. RESULTS: The median age was 72 years, and 116 patients (83.5%) were male. Based on the etiology of liver disease, 84 (60.4%) and 55 patients (39.6%) were assigned to the viral infection and nonviral infection groups, respectively. The significant extents in patient characteristics were not observed in both groups. The objective response rate per mRECIST and progression-free survival (PFS) did not differ significantly between the viral infection and nonviral infection groups (36.0 vs. 33.0%, p = 0.85; and 7.6 vs. 7.5 months, p = 0.94, respectively). The 1-year survival rates were 68.7% (95% confidence interval [CI] 57.7-79.7%) in the viral infection group and 59.5% (95% CI 45.2-73.8%) in the nonviral infection group. The viral infection group was not a significant factor associated with the PFS or OS in a multivariate analysis. CONCLUSIONS: Lenvatinib shows no significant difference in response between patients with and without viral infection. Treatment strategies based on the etiology of liver disease may lead to good clinical outcome.

Changes of 18 F-fluoro-2-deoxyglucose position-emission tomography findings by the eradication of Helicobacter pylori in the stomach.

PURPOSE: Helicobacter pylori (HP) infection is reported to increase 18 F-fluoro-2-deoxyglucose (FDG) accumulation in the stomach. The accumulation of FDG by positron-emission tomography (FDG-PET) in the stomach for the voluntary health examinees of cancer checkup was examined before and after the HP eradication. SUBJECTS AND METHODS: From March 2013 to October 2015, eighty-one subjects were performed FDG-PET to detect cancer at the health checkup. All of them were also surveyed by esophagogastroduodenoscopy. Subjects were classified as the 33 cases of HP positive (group A), 38 cases of originally negative (group B), and the 10 negative cases by HP eradication therapy (group C). Group A was treated by combination of amoxicillin, clarithromycin, and proton pump inhibitor for a week, and all of them eradicated HP. A part of group A (n = 7) was serially performed FDG-PET one to five years after the treatment and compared the maximum standard uptake value of FDG (SUV) around the fundic gland region. RESULTS: SUV of group A (3.55 ± 0.69) was significantly higher than those of both group B (2.96 ± 0.72) and group C (2.89 ± 0.51) (p < 0.01, respectively). Groups B and C are almost comparable and showed no significant difference during the course. In group A, HP eradication significantly decreased the SUV to 3.1 ± 0.43 (P < .01). SUV after the eradication was significantly reduced (P < .01) in the mild to moderate atrophy (C1-C3) group according to Kimura and Takemoto classification of chronic gastritis of group A. Although SUV in the advanced atrophy group (O1-O3) tended to decline after the eradication, the change was not significant. CONCLUSION: HP-infected stomach showed higher FDG uptake in the fundic gland region and HP eradication decreased the uptake in the mild to moderate atrophic gastritis but not in the severe atrophic gastritis.

Therapeutic efficacy of lenvatinib as third-line treatment after regorafenib for unresectable hepatocellular carcinoma progression.

AIM: Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure. METHODS: From June 2017 to October 2020, 63 patients with Child-Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R-L group, n = 47) and those who did not receive lenvatinib after regorafenib (non-R-L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting. RESULTS: Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R-L and non-R-L groups, whereas the albumin-bilirubin score, Child-Pugh class, and tumor burden were not. Progression-free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R-L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin-bilirubin grade 2b (score >-2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment. CONCLUSION: These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.

Favorable outcome of retreatment by direct-acting antivirals for hepatitis C patients with daclatasvir plus asunaprevir combination therapy failure.

AIM: In patients with hepatitis C virus, treatment failure of daclatasvir plus asunaprevir combination therapy (DCV + ASV) seems to become intractable due to the induction of resistance-associated substitutions. This study aimed to investigate the outcomes of retreatment with direct-acting antivirals (DAAs) in patients with DCV + ASV therapy failure, as well as changes in drug resistance mutations. METHODS: We retrospectively analyzed 44 patients re-treated with DAAs after DCV + ASV failure between December 2015 and April 2018. All patients were analyzed for amino acid substitutions, and additional treatment regimens were selected based on the results and current treatment guidelines. RESULTS: The sustained virological response rate with second-line treatment was 81.8% (36/44), and relapse occurred in five of 16 patients who received sofosbuvir/ledipasvir and three of seven patients who received DCV/ASV/beclabuvir. Third- and fourth-line treatments were also tried in relapsed cases, and the overall sustained virological response rates were 90.9% (40/44) and 93.2% (41/44), respectively. A high rate of viral clearance was eventually observed. Before second-line treatment, the prevalence of mutations in the NS5A and NS3/4A regions was 100% (44/44) and 86.4% (38/44), respectively. There was no significant increase in the number of amino acid substitutions in patients for whom second-line treatment failed. CONCLUSIONS: Amino acid substitutions were frequently observed in patients with DCV + ASV failure, but most patients achieved a sustained virological response after retreatment with DAAs. Although the spread of drug-resistant viruses due to unsuccessful DAA treatment was a matter of concern, most cases of DCV + ASV failure were overcome with additional treatment.

Analyses of objective response rate, progression-free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study.

AIM: The aim of this study was to investigate the predictive factors of objective response rate (ORR) and progression-free survival (PFS), and the correlation of albumin-bilirubin (ALBI) grade with decreased appetite and fatigue in hepatocellular carcinoma patients treated with lenvatinib. METHODS: From March 2018 to December 2018, a total of 94 patients was included in this retrospective multicenter study. RESULTS: The median age of all patients was 73 years (interquartile range 66-79.3 years), and approximately 78% patients were men. The ALBI grade was 1, 2, and 3 in 27 (28.7%), 64 (68.1%), and three patients (3.2%), respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate, and advanced in one (1.1%), 22 (23.4%), and 71 patients (75.5%), respectively. Best radiological response was determined to complete response, partial response, stable disease, and progressive disease in 0 (0.0%), 24 (30.4%), 38 (48.1%), and 17 patients (21.5%), respectively, giving the ORR of 30.4%. The 3-, 6-, and 12-month PFS was calculated to be 78.7% (95% CI 70.3-87.1%), 46.7% (95% CI 36.1-57.3%), and 17.4% (95% CI 6.6-28.2%). Multivariate analysis showed that the Barcelona Clinic Liver Cancer intermediate stage was shown to be the only significant factor affecting the ORR (odds ratio 3.78, 95% CI 1.14-12.5, P = 0.030) and PFS (hazard ratio 0.49, 95% CI 0.26-0.94, P = 0.030). The incidence of all grades of decreased appetite and fatigue was significantly less in patients with ALBI grade 1 compared with ALBI grade 2 + 3. CONCLUSIONS: The Barcelona Clinic Liver Cancer intermediate stage was the predictive factor affecting the ORR and PFS, and ALBI grade was a good predictive factor affecting the incidence of fatigue and decreased appetite.

Factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization: A retrospective cohort study.

AIM: This study aimed to investigate the factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization (B-TACE). METHODS: Sixty-six patients treated with B-TACE at a Japanese tertiary referral hospital between January 2011 and August 2015 were included in this retrospective cohort study. RESULTS: The overall response was classified as complete response, partial response, stable disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11 (16.7%) patients, respectively. The response rate was 63.6%, and the disease control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95% confidence interval [CI], 1.26-15.7; P = 0.021) and α-fetoprotein level (HR, 11.40; 95% CI, 2.75-46.9; P < 0.001) were significantly associated with the tumor response in a multivariate analysis. The 1-, 2-, and 3-year survival rates were 76.8% (95% CI, 64.5-85.3%), 57.3% (95% CI, 42.3-69.7%), and 46.7% (95% CI, 30.7-61.2%), respectively. The median survival time was 902 days. Albumin (≥3.4 g/dL) (HR, 0.28; 95% CI, 0.12-0.63; P = 0.002) and overall response (complete response and partial response) (HR, 0.33; 95% CI, 0.16-0.71; P = 0.004) were factors significantly associated with overall survival in a multivariate analysis. No mortalities were observed, but biloma requiring percutaneous transhepatic biliary drainage occurred in one patient (1.5%). CONCLUSION: Balloon-occluded transcatheter arterial chemoembolization may exert a good antitumor effect and result in good overall survival in select hepatocellular carcinoma patients.

Indirect activation of pregnane X receptor in the induction of hepatic CYP3A11 by high-dose rifampicin in mice.

Rifampicin (RIF), a typical ligand of human pregnane X receptor (PXR), powerfully induces the expression of cytochrome P450 3A4 (CYP3A4) in humans. Although it is thought that RIF is not a ligand of rodent PXR, treatment with high-dose RIF (e.g. more than 20 mg/kg) increases the expression of CYP3A in the mouse liver. In this study, we investigated whether the induction of CYP3A by high-dose RIF in the mouse liver is mediated via indirect activation of mouse PXR (mPXR). The results showed that high-dose RIF increased the expression of CYP3A11 and other PXR-target genes in the liver of wild-type mice but not PXR-knockout mice. However, the results of reporter gene and ligand-dependent assembly assays showed that RIF does not activate mPXR in a ligand-dependent manner. In addition, high-dose RIF stimulated nuclear accumulation of mPXR in the mouse liver, and geldanamycin and okadaic acid attenuated the induction of Cyp3a11 and other PXR-target genes in primary hepatocytes, suggesting that high-dose RIF triggers nuclear translocation of mPXR. In conclusion, the present study suggests that high-dose RIF stimulates nuclear translocation of mPXR in the liver of mice by indirect activation, resulting in the transactivation of Cyp3a11 and other PXR-target genes.

[Is Balloon-Occluded Transcatheter Arterial Chemoembolization Effective in Patients with Hepatocellular Carcinoma That Is Unresponsive to Conventional Transcatheter Arterial Chemoembolization ?]

We previously reported that the antitumor response of balloon-occluded transcatheter arterial chemoembolization(BTACE) is better than that of conventional transcatheter arterial chemoembolization(C-TACE). Thus far, little attention has been paid on the efficacy of B-TACE using the same antitumor agents for hepatocellular carcinoma(HCC)that is unresponsive to C-TACE, which is defined as C50% necrosis of the targeted nodules or the appearance of new lesions in the liver 1-3 months following one C-TACE procedure. Therefore, this study focused on the efficacy of B-TACE using the same antitumor agents for HCC that is unresponsive to C-TACE. Fourteen patients treated with B-TACE at our institution were retrospectively investigated between January 2011 and August 2015. The median age was 76(interquartile range[IQR]70-79)years, and 9 patients(64.3%)were men. A total of 9(64.3%)and 5(35.7%)patients had the Child-Pugh class A and B, respectively. The median maximum tumor diameter was 30(IQR 18-40)mm, and 4(28.6%), 3(21.4%), 0(0.0%), and 7(50.0%) patients had 1, 2, 3, andB4 tumors, respectively. The antitumor effects were CR, PR, SD, and PD in 6(42.9%), 1(7.1%), 3 (21.4%), and 7(28.6%)patients, respectively. The response and disease control rates were 50% and 71.4%, respectively. Our results suggest that B-TACE is an effective modality for the treatment of HCC that is unresponsive to C-TACE.

Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma.

AIM: Amino acid transporters play an important role in tumor progression and survival of cancer cells. However, the prognostic significance of L-type amino acid transporter 1 (LAT1), system ASC amino acid transporter-2 (ASCT2) and xCT expression in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the clinicopathological significance of these amino acid transporters in patients with HCC. METHODS: We examined 84 patients with surgically resected HCC. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67 and microvessel density (MVD) determined by CD34. RESULTS: LAT1, 4F2hc, ASCT2 and xCT were positively expressed in 61% (50/84), 77% (65/84), 63% (53/84) and 65% (55/84), respectively. Positive LAT1 expression was significantly associated with 4F2hc expression, Ki-67 and the serum albumin. By univariate analysis, LAT1 expression, disease stage and albumin had a significant relationship with overall survival. Tumor size, disease stage, portal vein invasion, albumin and α-fetoprotein had a significant relationship with progression-free survival. Multivariate analysis confirmed that LAT1 expression is an independent and significant prognostic factor for predicting worse outcome after surgery. CONCLUSION: LAT1 can serve as a significant prognostic marker for predicting negative prognosis after surgery.

Adolescents with chronic hepatitis C might be good candidates for direct-acting antiviral therapy.

Three Japanese adolescents with chronic hepatitis C were treated by direct-acting antivirals (DAAs). No adverse events or laboratory abnormalities were observed during and after DAA therapy, and a sustained virological response was achieved in all cases. The emotional functioning of the patients and their mothers were improved after DAA therapy.

A case of unresectable combined hepatocellular and cholangiocarcinoma treated with atezolizumab plus bevacizumab.

An 81-year-old man initially underwent right hepatic lobectomy for liver cancer and was pathologically diagnosed with combined hepatocellular and cholangiocarcinoma (CHC). At 13 months after resection, multiple lymph node metastases were observed. We started atezolizumab plus bevacizumab (Atez/Bev), achieving a 7.5-month progression-free survival. Atez/Bev might exhibit efficacy for CHC patients.

Changes of esophageal varices in hepatitis C patients after achievement of a sustained viral response by direct-acting antivirals.

Objectives: The changes in portal hypertension after achieving a sustained viral response (SVR) by direct-acting antivirals (DAAs) have not been fully elucidated. Consequently, noninvasive and inexpensive predictors need to be investigated. We therefore explored factors associated with the progression of EVs after the achievement of an SVR with DAAs in patients with chronic hepatitis C. Methods: Eighty-nine patients, who had achieved an SVR with DAAs and could have their esophagogastroduodenoscopy (EGD) findings compared between before DAAs administration and after achieving an SVR achievement were enrolled in this study. We compared the patients with and without EVs progression. Furthermore, the cumulative progression rates of EVs were also analyzed. Results: The fibrosis-4 index (FIB-4) before DAAs administration was the only significant factor for the progression of EVs after an SVR (odds ratios: 1.2, 95% confidence intervals: 1.05-1.38, p = 0.01). In a receiver operating characteristics analysis, the cut-off of FIB-4 for the progression of EVs was 8.41 (sensitivity: 0.63, specificity: 0.86, positive predictive value: 0.31, negative predictive value: 0.96), namely EVs of those with more than 8.41 of FIB-4 progressed and those with less than 8.41 of FIB-4 did not. Conclusions: As patients with FIB-4 ≥ 8.41 may have progressions of EVs, periodic surveillance by EGD should be continued in such cases, even after an SVR is achieved.

Constitutive active/androstane receptor promotes hepatocarcinogenesis in a mouse model of non-alcoholic steatohepatitis.

The nuclear receptor constitutive active/androstane receptor (CAR) acts as a sensor of toxic byproducts derived from the endogenous metabolism and exogenous chemicals. We previously reported that CAR is responsible for exacerbating hepatic injury and fibrosis in a dietary model of non-alcoholic steatohepatitis (NASH) via upregulation of lipid peroxidation. In this study, we investigated the pathological roles of the CAR in the development of hepatocellular carcinoma in NASH model. CAR+/+ and CAR-/- mice were fed methionine- and choline-deficient (MCD) diet after tumor initiation with a single dose of the genotoxic carcinogen diethylnitrosamine (DEN) at 2 weeks of age. Interestingly, the MCD diet dramatically promoted DEN-induced hepatocarcinogenesis in CAR+/+ mice. However, the deletion of CAR leads to a significantly lower tumor incidence and smaller tumor diameter. Hepatocytes of MCD-treated-CAR+/+ mice showed a significantly higher staining frequency of Ki-67, a marker of cell proliferation, and exhibited a higher expression of c-Myc and FoxM1 transcripts compared with MCD-treated CAR-/- mice. Immunohistochemistry revealed the nuclear translocation of CAR thus suggesting that the activation of CAR signaling increased in the hepatocytes of CAR+/+ mice fed MCD diet. In addition, in vitro experiments using the CAR stably expressed cell line with TCPOBOP have suggested that CAR activation directly leads to cell proliferation. Survival was significantly lower in the CAR+/+ mice fed the MCD diet in comparison with the CAR-/- mice. Taken together, these results suggest that CAR may therefore play a critical role in the hepatocarcinogenesis of the murine NASH model via the upregulation of cell proliferation.

Successful treatment of Japanese hemophilia patient co-infected with HIV and HCV genotype 4a by glecaprevir/pibrentasvir therapy.

Although direct-acting antiviral (DAA)-based anti-hepatitis C virus (HCV) therapies are very effective for patients with genotypes 1 and 2, evidence of the efficacy of DAA-based therapy for the special population of patients with genotypes 3-6 is insufficient due to the relatively small number of these subjects in Japan. Human immunodeficiency virus (HIV)/HCV-co-infected patients are recommended to be treated as HCV-mono-infected patients by the latest version of the Japan Society of Hepatology guidelines. However, evidence of efficacy in patients with HIV/HCV genotype 3-6 co-infection is insufficient. Currently, HCV genotypes 3-6 can be treated with two DAA-based therapies, including glecaprevir (GLE)/pibrentasvir (PIB) therapy in Japan. We experienced a relatively rare case of a Japanese hemophilia patient co-infected with HIV/HCV genotype 4a. We evaluated resistance-associated substitutions (RASs) against GLE and PIB before GLE/PIB therapy and found that he had no RASs. He was treated with 12 weeks of GLE/PIB therapy and achieved a sustained virologic response at post-treatment weeks 24. Although the treatment was well tolerated, the patient developed hyper-low-density lipoproteinemia that was probably associated with HCV elimination during the therapy. Additional studies are needed to confirm the efficacy and safety of GLE/PIB therapy for this special population in Japan.

An Autopsy Case of Multicentric Castleman Disease Presenting with Severe Jaundice.

A 70-year-old man with multicentric Castleman disease (MCD) was admitted to our hospital with jaundice and ascites. Elevations in his bilirubin and interleukin-6 levels were noted, and computed tomography revealed hepatic atrophy and portal vein and bile duct disorders. Steroid therapy was started for MCD, but he died of hepatic failure. An autopsy revealed that the MCD activity was mild, but advanced fibrosis and cholestasis were observed in the liver. Mild infiltration of interleukin-6-positive plasma cells was noted in the highly fibrotic area of the liver. Although rare, liver and biliary tract damage may be also considered organ disorders of MCD.

Effect of 48-week pemafibrate on non-alcoholic fatty liver disease with hypertriglyceridemia, as evaluated by the FibroScan-aspartate aminotransferase score.

BACKGROUND AND AIM: This retrospective study investigated the effect of 48-week pemafibrate therapy in non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia, as evaluated by the FibroScan-aspartate aminotransferase (FAST) score. METHODS: A total of 31 NAFLD patients who were treated with pemafibrate in Gunma Saiseikai Maebashi Hospital and Kusunoki Hospital from September 2018 to April 2020 were included in the current study. We used the FAST score, which is a novel index of steatohepatitis that can be calculated based on the AST value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), to evaluate the effect of pemafibrate treatment. RESULTS: The median age was 64.0 (interquartile range [IQR] 55.0-75.0) years and 14 patients (45.2%) were male. Median body mass index was 26.8 (IQR 23.8-28.8). Hypertension and diabetes mellitus were detected in 14 (45.2%) and five (16.1%) patients, respectively. Fasting triglyceride and high-density lipoprotein cholesterol were significantly improved (P < 0.001 and 0.013, respectively) and the AST, alanine aminotransferase (ALT), alkaline phosphatase, and γ-glutamyl transpeptidase values were significantly decreased during pemafibrate treatment (P = 0.041, <0.001, <0.001, and <0.001, respectively). While the LSM value and CAP value did not differ to a statistically significant extent (P = 0.19 and 0.140, respectively), the FAST score was significantly improved during pemafibrate treatment (P = 0.029). The delta FAST score was found to be correlated with the variations of ALT (r = 0.504, P = 0.005), which represents the effect of pemafibrate. CONCLUSIONS: Pemafibrate improved the FAST score due to the hepatic anti-inflammatory effect, indicating that pemafibrate may prevent disease progression in NAFLD patients with hypertriglyceridemia.

Impact of Pemafibrate in Patients with Hypertriglyceridemia and Metabolic Dysfunction-associated Fatty Liver Disease Pathologically Diagnosed with Non-alcoholic Steatohepatitis: A Retrospective, Single-arm Study.

Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline [AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively], especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.

The first reported case of Noonan syndrome complicated with hepatocellular carcinoma.

Noonan syndrome is a genetic multisystem disorder and is associated with mutation of genes encoding the proteins in the RAS-MAPK pathway. We reported the first case of Noonan syndrome complicated with hepatocellular carcinoma.

Follow-up after Direct-acting Antiviral Treatment for Chronic Hepatitis C Virus Infection: Most Patients Are Followed Appropriately.

Objective Chronic hepatitis C virus (HCV) infection carries a residual risk of hepatocarcinogenesis even after viral elimination, so appropriate follow-up is necessary. The present study investigated the current hospital visits and hepatocarcinogenesis status of patients who received daclatasvir plus asunaprevir treatment (DCV+ASV) to determine whether or not appropriate follow-up was being performed. Methods We retrospectively analyzed hepatocarcinogenesis, the overall survival, and the length of hospital visits in 442 patients who applied for the medical expense subsidy system for viral hepatitis and received DCV+ASV treatment in Gunma Prefecture between October 2014 and December 2015. This also included 61 patients who had a history of hepatocellular carcinoma (HCC). Results Among 442 patients, 388 achieved a sustained viral response (SVR) by DCV+ASV therapy (87.8%), and 95.9% achieved an SVR if additional treatment was included. HCC was found in 75 cases (17.0%). A history of HCC, the FIB-4 index and the treatment effect SVR were determined to be factors affecting the incidence of HCC. Regarding the follow-up rate, 89.9% of patients continued to regularly visit the hospital after 5 years of treatment. However, patients ≤60 years old had significantly lower persistence rates than older patients. The persistence rate of hospital visits to the same institution was 67.7% over a 5-year period, which was significantly better in small and medium-sized institutions than in large, specialized institutions (71.7% vs. 63.9%, p=0.039). Conclusion Patients with direct-acting antiviral treatment generally received adequate follow-up, but younger patients had a slightly higher rate of follow-up interruption and were considered to need support.