記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.

DOI： 10.1371/journal.pone.0292019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this retrospective multicenter study was to clarify the antifibrotic effect and long-term outcome of sodium glucose cotransporter 2 inhibitors (SGLT2-Is) in patients with nonalcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Of the 1262 consecutive patients with T2DM who recently received SGLT2-Is, 202 patients with NAFLD had been receiving SGLT2-Is for more than 48 weeks and were subjected to this analysis. Furthermore, 109 patients who had been on SGLT2-I therapy for more than 3 years at the time of analysis were assessed for the long-term effects of SGLT2-Is. Significant decreases in body weight, liver transaminases, plasma glucose, hemoglobin A1c, and Fibrosis-4 (FIB-4) index were found at week 48. Overall, the median value of FIB-4 index decreased from 1.42 at baseline to 1.25 at week 48 (p < 0.001). In the low-risk group (FIB-4 index < 1.3), there was no significant change in the FIB-4 index. In the intermediate-risk (≥1.3 and <2.67) and high-risk (≥2.67) groups, the median levels significantly decreased from 1.77 and 3.33 at baseline to 1.58 and 2.75 at week 48, respectively (p < 0.001 for both). Improvements in body weight, glucose control, liver transaminases, and FIB-4 index were found at 3 years of SGLT2-I treatment. In the intermediate-risk and high-risk groups (≥1.3 FIB-4 index), the FIB-4 index maintained a significant reduction from baseline throughout the 3 years of treatment. Conclusion: This study showed that SGLT2-Is offered a favorable effect on improvement in FIB-4 index as a surrogate marker of liver fibrosis in patient with NAFLD complicated by T2DM, especially those with intermediate and high risks of advanced fibrosis, and this antifibrotic effect is sustained for the long term.

DOI： 10.1002/hep4.2069

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

DOI： 10.1111/hepr.13840

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aim: This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods: This was a single-arm, open-label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24-week trial. Results: Body weight and levels of liver-related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment-insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis-4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1-2 transient gastrointestinal disorders. Conclusions: Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.

DOI： 10.1002/jgh3.12780

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima's pruritus score. Nalfurafine hydrochloride 2.5 μg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima's pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride.

DOI： 10.1038/s41598-022-11431-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

DOI： 10.1038/s41598-021-95581-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: This study aimed to elucidate the clinical importance of muscle volume loss (pre-sarcopenia) in patients receiving lenvatinib as treatment for unresectable hepatocellular carcinoma (u-HCC). METHODS: Of 437 u-HCC patients treated with lenvatinib at specific institutions in Japan between March 2018 and May 2020, 151 with available computed tomography imaging data from the time of lenvatinib introduction were enrolled. Pre-sarcopenia was diagnosed based on a previously reported cut-off value calculation formula [psoas muscle area at level of middle of third lumbar vertebra (cm2 )/height (m)2 ]. Clinical features and prognostic factors for overall survival (OS) with inverse probability weighting were investigated retrospectively for their relationship with pre-sarcopenia. RESULTS: Cox hazard multivariate analysis showed alpha-fetoprotein (≥400 ng/mL) (hazard ratio [HR] 2.271, P < 0.001), Barcelona Clinic Liver Cancer stage (C and D) (HR 1.625, P = 0.018), and positive for pre-sarcopenia (HR 1.652, P = 0.042) to be significant prognostic factors. OS rates for the pre-sarcopenia group (n = 41) were worse than those for the non-pre-sarcopenia group (n = 110) (0.5-, 1-, and 1.5-year OS: 72.5%, 27.9%, and 7.0% vs 80.7%, 56.7%, and 46.1%, respectively; P < 0.001), as was progression-free survival (P = 0.025). Time to stopping lenvatinib or disease progression was better in the non-pre-sarcopenia group (0.5-, 1-, and 1.5-year OS: 48.0%, 24.5%, and 8.4% vs 20.0%, 10.3%, and 4.2%, respectively; P < 0.001). Also, the frequency of the adverse event appetite loss (any grade) was greater in the pre-sarcopenia group (43.9% vs 18.2%, P = 0.003). CONCLUSION: Pre-sarcopenia was shown to be a significant prognostic factor in patients treated with lenvatinib for u-HCC.

DOI： 10.1111/jgh.15336

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sarcopenia worsens patient prognoses in chronic liver disease. This study aimed to elucidate the effects of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated cirrhosis. METHODS: Thirty-three patients were entered into the study based on the criteria and then randomly assigned to two groups: Group A (n = 17), the control group, and Group B (n = 16), those who received oral native vitamin D3 at a dose of 2000 IU once a day for 12 months. RESULTS: SMI values in Group B were significantly increased at 12 months (7.64 × 10-3). The extent of changes in the SMI and grip strength in Group B were significantly greater than that in Group A at 12 months (p = 2.57 × 10-3 and 9.07 × 10-3). The median change rates in the SMI were +5.8% and the prevalence of sarcopenia was significantly decreased from 80.0% (12/15) to 33.3% (5/15; p = 2.53 × 10-2) in Group B. CONCLUSIONS: Vitamin D supplementation might be an effective and safe treatment option for patients with decompensated cirrhosis to increase or restore the skeletal muscle volume and strength or prevent the muscle volume and strength losses.

DOI： 10.3390/nu13061874

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Lenvatinib is used for unresectable hepatocellular carcinoma (u-HCC) as first-line, as well as second- and third-line therapy in Japan. We evaluated the therapeutic efficacy of newly developed ramucirumab when given after lenvatinib for post-progression treatment. METHODS: Of 385 patients with u-HCC and treated with lenvatinib at 16 different institutions in Japan between May 2018 and January 2020, 28 who received ramucirumab as the next treatment were enrolled and therapeutic responses were evaluated in a retrospective manner. RESULTS: The median age of the 28 patients given ramucirumab was 70 years and the median albumin-bilirubin score was -2.19. Of the 28 patients, 23 were male, 21 were classified as Child-Pugh A and 7 as Child-Pugh B, and 25 were Barcelona Clinic Liver Cancer Stage C. Ramucirumab was given as second-line therapy in 14, third-line in 9, and fourth-line in 5. Therapeutic response was obtained in only 26 patients; the objective response rate was 3.8% (1/26) and the disease-control rate was 42.3% (11/26), with a median period to progression of 2.0 months. The reasons for discontinuation of ramucirumab were progression of disease in 16 and Grade 3 adverse events (gastrointestinal bleeding, ascites) in 2. CONCLUSIONS: The anticipated therapeutic efficacy of ramucirumab for post-progression treatment following lenvatinib was not seen in our early experience.

DOI： 10.1093/gastro/goaa042

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). METHODS: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. RESULTS: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). CONCLUSION: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

DOI： 10.1159/000513355

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Lenvatinib, a newly developed molecularly targeted agent, has become available as a first-line therapy in patients with unresectable hepatocellular carcinoma (HCC). The platelet-to-lymphocyte ratio (PLR) has been associated with poor outcome in various malignancies, including HCC. In this study, we investigated the ability of PLR to predict outcomes in patients with unresectable HCC who received lenvatinib. METHODS: Multivariate survival analysis was performed in 283 patients with unresectable HCC who received lenvatinib. In addition, the utility of PLR for predicting survival was clarified using an inverse probability weighting (IPW) analysis. RESULTS: Cumulative overall survival at 100, 200, 300, 400, and 500 days was 95.2, 83.8, 68.3, 60.3, and 49.9%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that PLR (≥150) [hazard ratio, 1.588; 95% confidence interval (CI), 1.039-2.428; P = 0.033], α-fetoprotein level, and Barcelona clinic liver cancer stage were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high PLR (P = 0.029). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that PLR (≥150) (hazard ratio, 1.396; 95% CI, 1.051-1.855; P = 0.021) was significantly associated with overall survival. Conversely, univariate analysis with Cox proportional hazards modeling adjusted only by IPW showed that PLR (≥150) (hazard ratio, 1.254; 95% CI, 1.016-1.549; P = 0.035) was significantly associated with progression-free survival. PLR values were not independently associated with therapeutic responses before or after IPW-adjusted logistic regression analysis. CONCLUSIONS: PLR predicted overall survival in patients with unresectable HCC who received lenvatinib.

DOI： 10.1097/MEG.0000000000001734

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. METHODS: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. RESULTS: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. CONCLUSIONS: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV.

DOI： 10.1002/jgh3.12443

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

DOI： 10.2169/internalmedicine.5432-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM. METHODS: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors. RESULTS: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1-6.7 kPa) (p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight (p < 0.001), alanine aminotransferase (p = 0.02), uric acid (p < 0.001), and Fibrosis-4 (FIB-4) index (p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group (p < 0.001). CONCLUSION: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.

DOI： 10.1177/20420188211000243

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension. METHODS: The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg. RESULTS: The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. CONCLUSIONS: Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.

DOI： 10.1111/hepr.13560

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

肝性胸水の中でも内科的治療に反応しない難治性肝性胸水は患者のQOLを著しく障害し、その生存期間は約6ヵ月と予後不良である。今回我々は、2001年から2015年までに当科において難治性肝性胸水を適応としてTIPSを行った肝硬変20例についてその長期成績を検討した。対象の平均年齢は61.1±10.8歳、Child-Pughスコア(CPS)は9.7±1.5であった。全例において手技は成功し術後胸水穿刺は不要となった。1年生存率、生存期間中央値はそれぞれ69%、23.2ヵ月であった。対象を術前CPS11点以下(n=16)に限定するとそれぞれ73%、27.8ヵ月と成績は向上した。術前CPSが12点であった4例中2例が肝不全進行により術後60日以内に死亡した。以上より、TIPSは難治性肝性胸水の治療に有用であり生命予後を改善する可能性があるが、対象はCPS11点以下に限定する事が望ましいと思われた。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00263&link_issn=&doc_id=20200814030002&doc_link_id=10.2957%2Fkanzo.61.399&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.61.399&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Lenvatinib, a newly developed molecularly targeted agent, has become available for patients with unresectable hepatocellular carcinoma (HCC). Neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor outcomes in numerous malignancies. In this study, we investigated the impact of NLR on associating outcomes in patients with HCC treated with lenvatinib. METHODS: A total of 237 patients with HCC treated with lenvatinib were included. We performed univariate and multivariate analyses in this cohort. In addition, we clarified appropriate cut-off NLR levels for associating overall survival using hazard ratio (HR) spline curves. RESULTS: Cumulative overall survival at 100, 200 and 300 days was 95.2%, 83.4% and 66.6% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.874; 95% confidence interval [CI], 1.097-3.119), α-foetoprotein ≥ 400 ng/mL (HR, 1.969; 95% CI, 1.188-3.265) and modified albumin-bilirubin grade 2b or 3 (HR, 2.123; 95% CI, 1.267-3.555) were independently associated with overall survival. Cumulative progression-free survival at 100, 200 and 300 days was 72.4%, 49.8% and 38.7% respectively. Multivariate analysis showed that NLR ≥ 4 (HR, 1.897; 95% CI, 1.268-2.837) and BCLC stage ≥ C (HR, 1.516; 95% CI, 1.028-2.236) were independently associated with progression-free survival. Disease control rate was significantly different between the patients with low NLR (<4) (85.5%) and high NLR (≥4) (67.3%) (P = .007). Spline curve analysis revealed that NLR of approximately 3.0-4.5 is an appropriate cut-off for associating overall survival. CONCLUSIONS: NLR can be associated with outcomes in patients with HCC treated with lenvatinib.

DOI： 10.1111/liv.14405

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Post-progression treatment following tyrosine-kinase inhibitor (TKI) failure in patients with unresectable hepatocellular carcinoma (u-HCC) is important to prolong post-progression survival (PPS), which has a good correlation with overall survival (OS). This study aimed to elucidate the clinical features of progressive disease (PD) in patients treated with lenvatinib (LEN). MATERIALS/METHODS: From March 2018 to June 2019, 156 u-HCC patients with Child-Pugh A were enrolled (median age: 71 years, Child-Pugh score 5:6 = 105:51, BCLC A:B:C = 8:56:92, modified albumin-bilirubin grade (mALBI) 1:2a:2b = 59:42:55, past history of sorafenib:regorafenib = 57:17). Clinical features were retrospectively evaluated. RESULTS: The median observation period was 8.5 months. Median OS was not obtained, while median time to decline to Child-Pugh B (CPB) was 11.4 months, median time to progression (TTP) was 8.4 months, and the period of LEN administration was 7.3 months. When we compared predictive values for time to decline to CPB based on Child-Pugh score and mALBI, values for Akaike information criterion (AIC) score and c-index of mALBI were superior as compared to Child-Pugh score (AIC: 592.3 vs. 599.7) (c-index: 0.655 vs. 0.597). Of the 73 patients with PD, 32 (43.8%) showed no decline to CPB or death. After excluding 3 without alpha-fetoprotein data at PD determination, only 14 (20.0%) of 70 showed REACH-2 eligibility. Non-mALBI 1/2a at the start of LEN was a significant risk factor for decline to CPB during LEN treatment (HR 2.552, 95% CI: 1.577-4.129; p < 0.001). CONCLUSION: Introduction of TKI therapy including LEN for u-HCC patients with better hepatic function (mALBI 1/2a: ALBI score ≤-2.27), when possible, increases the chance of undergoing post-progression treatment, which can improve PPS.

DOI： 10.1159/000503031

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Lenvatinib has become available as first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). However, the safety and efficacy of lenvatinib in elderly patients with HCC has not been sufficiently investigated. We compared the frequency of adverse events and prognosis between elderly and non-elderly patients with HCC who received lenvatinib. METHODS: A total of 100 patients with HCC who received lenvatinib were selected using propensity score matching: 50 patients were elderly (age ≥75 years) and 50 patients were non-elderly. RESULTS: In the elderly group, >20% of patients experienced fatigue (36.0%), decreased appetite (26.0%), hypothyroidism (24.0%), proteinuria (22.0%), palmar-plantar erythrodysesthesia (22.0%), and hypertension (20.0%) of any grade as treatment-related adverse events. In addition, >10% of patients experienced grade ≥3 treatment-related fatigue (12.0%). In the non-elderly group, >20% of patients experienced palmar-plantar erythrodysesthesia (42.0%), fatigue (28.0%), decreased appetite (22.0%), and diarrhea (20.0%) of any grade as treatment-related adverse events. In addition, >10% of patients experienced grade ≥3 treatment-related proteinuria (10.0%). There were no significant differences between the elderly and non-elderly groups in the frequency of adverse events. Regarding overall and progression-free survival, there were no significant differences between the elderly and non-elderly groups (hazard ratio 0.972, 95% confidence interval 0.374-2.529; and hazard ratio 1.362, 95% confidence interval 0.687-2.700, respectively). Palmar-plantar erythrodysesthesia (hazard ratio 0.117, 95% confidence interval 0.015-0.916) was independently associated with overall survival in a multivariate analysis. CONCLUSIONS: Lenvatinib can be used safely and efficaciously regardless of age in patients with HCC.

DOI： 10.1111/hepr.13427

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera's prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. METHODS: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36). RESULTS: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were "not reached" (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = -0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. CONCLUSIONS: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.

DOI： 10.1159/000506293

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

DOI： 10.1111/jvh.13170

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u-HCC) by investigating real-world clinical features of patients. MATERIALS/METHODS: One hundred fifty two u-HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child-Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin-bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. RESULTS: Overall-response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine-kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649-13.02, P = 0.004) in Cox-hazard multivariate analysis. In patients with Child-Pugh A, c-index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without (P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m2 , P < 0.001), while patients with a hand-foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without (P = 0.007). CONCLUSION: Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.

DOI： 10.1002/cam4.2241

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although the presence of nonalcoholic fatty liver disease (NAFLD) is known to be related to subclinical atherosclerosis, the relationship between the severity of NAFLD and subclinical atherosclerosis is not clear. This study aimed to clarify the factors related to subclinical arteriosclerosis, including the histopathological severity of the disease and PNPLA3 gene polymorphisms, in NAFLD patients. We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness in 153 biopsy-proven NAFLD patients. The baPWV values were significantly higher in the advanced fibrosis group than in the less advanced group (median, 1679 cm/s vs 1489 cm/s; p = 5.49×10-4). Multiple logistic regression analysis revealed that older age (≥55 years) (p = 8.57×10-3; OR = 3.03), hypertension (p = 1.05×10-3; OR = 3.46), and advanced fibrosis (p = 9.22×10-3; OR = 2.94) were independently linked to baPWV ≥1600 cm/s. NAFLD patients were categorized into low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2) based on their risk factors, including older age, hypertension, and biopsy-confirmed advanced fibrosis. The prevalence of baPWV ≥1600 cm/s was 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high-risk group. Non-invasive liver fibrosis markers and scores, including the FIB-4 index, NAFLD fibrosis score, hyaluronic acid, Wisteria floribunda agglutinin positive Mac-2-binding protein, and type IV collagen 7s, were feasible substitutes for invasive liver biopsy. Older age, hypertension, and advanced fibrosis are independently related to arterial stiffness, and a combination of these three factors may predict risk of arteriosclerosis in NAFLD patients.

DOI： 10.1371/journal.pone.0224184

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: We evaluated clinical factors related to improved prognosis of unresectable hepatocellular carcinoma patients (u-HCC), who were treated with tyrosine kinase inhibitor (TKI) sequential therapy, including lenvatinib (LEN). MATERIALS/METHODS: We enrolled 84 u-HCC cases treated with TKIs including LEN from March 2018 to January 2019 (median age 71 years, 63 males, Child-Pugh score (CPS) 5/6/7 = 62/21/1, tumor-node-metastasis stage of Liver Cancer Study Group of Japan 6th (TNM-LCSGJ) II/III/IVa/IVb = 12/30/5/37, Barcelona Clinic Liver Cancer stage B/C = 33:51). Clinical findings at introduction of the initial TKI were retrospectively evaluated. RESULTS: The median albumin-bilirubin (ALBI) score at introduction of the initial TKI (sorafenib [SOR]/LEN = 80/4) was -2.56, and the past number of transarterial catheter chemoembolization was 3 (IQR: 2-5) (second-line: regorafenib [REG]/LEN/SOR = 31/49/4, third-line: LEN/REG = 31:1). The total period of administration with TKIs showed a good relationship with overall survival (OS) (r = 0.946, 95% confidence interval [CI]: 0.918-0.965, p < 0.001). The prognosis of the entire cohort was good (estimated median survival time: 46.4 months, 1-/2-/3-year OS rate [OSR] = 87.7/63.0/57.2%). A modified-ALBI grade (mALBI) of 2b (ALBI score >-2.27) was the only significant factor at the start of the initial TKI for poor prognosis (hazard ratio 2.319, 95% CI: 1.064-5.052, p = 0.034), while CPS (≥6) was not. Although there was no significant difference in TNM-LCSGJ (p = 0.213), the prognosis of patients with mALBI 1/2a (n = 66) showed better prognosis as compared to those with mALBI 2b (n = 18) (1-year/2-year/3-year OSR = 89.1/69.8/66% vs. 82.4/47.1/23.5%, p = 0.029). CONCLUSION: Good hepatic function (mALBI 1/2a) at introduction of the initial TKI is a requirement for improved prognosis of u-HCC undergoing TKI sequential therapy.

DOI： 10.1159/000501281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Lenvatinib (LEN) has been developed for the treatment of unresectable hepatocellular carcinoma (u-HCC). We aimed to elucidate the relative change in hepatic reserve function early following LEN treatment in affected patients. MATERIALS/METHODS: From March 2018 to April 2019, 123 u-HCC patients (median age 71 years; male:female ratio 95:28; Child-Pugh score 5:6:7 = 65:50:8; modified albumin-bilirubin [mALBI] grade 1:2a:2b:3 = 44:28:50:1, Barcelona Clinic Liver Cancer stage A:B:C = 1:49:73) were enrolled. Relative changes in hepatic reserve function at 2 and 4 weeks after starting LEN were retrospectively evaluated. RESULTS: The median survival was 11.3 months. The Child-Pugh score declined from the start to 4 weeks after commencing LEN (score 5:6:7:8:9:≥10 = 65:50:8:0:0:0 vs. 50:39:22:8:0:4, p < 0.001). A comparison among ALBI scores at the start of LEN and those at 2 and 4 weeks revealed significant relative changes (-2.36 ± 0.45 to -2.20 ± 0.49 at 2 weeks, -2.15 ± 0.50 at 4 weeks, p < 0.001, Bonferroni method), while there was no significant difference between those at 2 and 4 weeks (p= 0.210, Bonferroni method). Assessments of relative changes of ALBI score in patients divided by mALBI grade 1, 2a, and 2b or more showed a significant decline in score regardless of grade (-2.82 ± 0.17 to -2.53 ± 0.34, p < 0.001; -2.46 ± 0.10 to -2.31 ± 0.33, p = 0.017; and -1.90 ± 0.26 to -1.75 ± 0.42, p= 0.009, respectively). CONCLUSION: Decline in hepatic function is common in the early stage (≤4 weeks, especially within 2 weeks) after introducing LEN. It is important to introduce molecular targeting agent drugs for u-HCC in patients with better hepatic function, who show transarterial catheter chemoembolization failure, as much as possible, along with consideration of the negative influence of LEN on the early response of hepatic function.

DOI： 10.1159/000502095

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: This study aimed to clarify the factors predictive of treatment response to tolvaptan (V2-receptor antagonist) for cirrhotic patients with hepatic edema in a real-world setting. METHODS: In this retrospective, multicenter study, tolvaptan was orally administered at a dose of 7.5 mg once a day. Patients with a decrease in body weight of 1.5 kg or greater from baseline were characterized as responders at day 7. RESULTS: Of 229 patients, 210 were subjected to this analysis. Patients consisted of 133 men and 77 women, with the median age of 67 years (range, 40-89 years). According to the Child-Pugh classification, five patients were classified as class A, 90 as class B, and 115 as class C. The frequencies of responders and nonresponders were 55.2% and 44.8%, respectively. Blood urea nitrogen (BUN) level was significantly lower in responders compared with nonresponders (P = 3.77 × 10-3 ). Using the receiver operating characteristic curve, the cutoff value of 28.2 mg/dL was the most useful in discriminating responders from nonresponders. Among 154 patients with BUN level of less than 28.2 mg/dL, 95 (61.7%) were responders. By contrast, among 56 patients with BUN level of 28.2 mg/dL or more, 21 (37.5%) were nonresponders (P = 2.70 × 10-3 ). On multivariate analysis, BUN level of <28.2 mg/dL and urine sodium >51 mEq/day were found to be independent factors associated with the response to tolvaptan. CONCLUSIONS: This study suggests that BUN level and urinary sodium excretion are closely associated with the response to tolvaptan in cirrhotic patients with hepatic edema.

DOI： 10.1111/jgh.14047

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: To evaluate the efficacy and safety of ledipasvir and sofosbuvir therapy for genotype 1b in chronic hepatitis C patients with chronic kidney disease (CKD) stage 3. METHODS: In a multicenter collaborative retrospective study, 706 patients who have received ledipasvir which is NS5A inhibitor, and sofosbuvir 400 mg which is NS5B nucleoside polymerase inhibitor daily for 12 weeks between September 2015 and January 2017 were subjected to this analysis. Virologic response and adverse events in patients with CKD stage 3 were compared with those in patients with CKD stages 1 and 2. RESULTS: The rates of sustained virologic response (SVR) were 97.0% in patients with CKD stage 1, 97.1% in patients with CKD stage 2, and 94.7% in patients with CKD stage 3, respectively. There were no significant differences in the SVR rates between CKD stages 1 and 2, and CKD stage 1 and stage 3. The incidence of adverse events over than grade 2 was 0% in patients with CKD stage 1, 0.5% in patients with CKD stage 2, and 3.0% in patients with CKD stage 3, respectively. For treatment and follow-up period, eGFR levels in the patients with CKD stage 3 were not worsened compared to those at baseline. CONCLUSION: This study suggested that the virologic response of ledipasvir and sofosbuvir in patients with CKD stage 3 was not inferior to those with CKD stages 1 and 2. In addition, administration of ledipasvir and sofosbuvir did not affect eGFR levels in the patients with CKD stage 3.

DOI： 10.1007/s12072-018-9859-9

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記述言語：日本語   出版者・発行元：(一社)日本門脈圧亢進症学会  

症例は74歳男性で、過去に肝細胞癌に対し肝右葉切除術を施行されていた。肝性胸水による呼吸困難で前医入院し、利尿剤投与にもかかわらず胸水コントロールがつかず、呼吸苦軽減のため週1回の穿刺排液を必要とした。難治性肝性胸水に対する治療として経頸静脈的肝内門脈大循環短絡術(TIPS)を考慮され、その検討を目的として当科に紹介入院となった。特に除外基準に抵触しないためTIPSを行った。TIPS作成後の脾静脈造影では良好なシャント血流を認め、後胃静脈血流の減量を認めた。TIPS後には尿量が増加し、胸水は順調に減少した。術後11日目にtolvaptanを休薬とするも胸水の増悪は認めなかった。肝性脳症を認めず全身状態も良好であったが、アンモニア値が若干上昇したため予防的にkanamycin、lactuloseを追加した。Furosemide、spironolactone投与下にて術後14日目に退院となった。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03767&link_issn=&doc_id=20170808340005&doc_link_id=10.11423%2Fjsph.23.167&url=https%3A%2F%2Fdoi.org%2F10.11423%2Fjsph.23.167&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) usually occurs in patients with metabolic syndrome. However, it can develop in relation with pancreaticoduodenectomy (PD) independent of insulin resistance. NAFLD/NASH potentially progresses to liver cirrhosis and subsequent end-stage liver disease, but in general the disease progression is very slow. We here report the case of a 57-year-old Japanese woman who underwent PD for pancreatic head cancer, subsequent to which she developed rapidly progressive NASH without prior liver diseases, resulting in death due to hepatic failure 5 months after PD. Marked body weight loss was a distinguishing clinical feature. Severe malnutrition induced by pancreatic exocrine insufficiency, postoperative eating disorder and exacerbation of diabetes mellitus were thought to be etiologically associated with the rapid progression of her disease. This case suggests the necessity of close hepatic surveillance as well as nutritional evaluation followed by prophylactic pancreatic enzyme replacement and nutritional supply after PD.

DOI： 10.1007/s12328-013-0421-y

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開催年月日： 2020年9月

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開催年月日： 2020年7月

記述言語：日本語  

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開催年月日： 2020年7月

記述言語：日本語  

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開催年月日： 2020年7月

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開催年月日： 2020年5月

記述言語：日本語  

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開催年月日： 2020年5月

記述言語：日本語  

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開催年月日： 2020年5月

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開催年月日： 2020年4月

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開催年月日： 2020年4月

記述言語：日本語  

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開催年月日： 2020年

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開催年月日： 2020年

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開催年月日： 2020年

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開催年月日： 2020年

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開催年月日： 2019年11月

記述言語：日本語  

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開催年月日： 2019年10月

記述言語：日本語  

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開催年月日： 2019年9月

記述言語：日本語  

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開催年月日： 2019年9月

記述言語：日本語  

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開催年月日： 2019年9月

記述言語：日本語  

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開催年月日： 2019年7月

記述言語：日本語  

71歳、女性。60歳時にC型肝硬変、食道静脈瘤、腹水、肝性脳症、肝動脈門脈短絡(A-Pシャント)と診断されたが食道静脈瘤硬化療法(EIS)と利尿剤投与などにより病状は安定していた。70歳時に再度EIS施行したところ腹水が増悪し、その後、利尿剤不耐性の難治性腹水となり当科へ入院となった(Child-Pughスコア12点)。TAEによるA-Pシャント塞栓術を施行したところ、肝静脈圧較差は26mmHgから19mmHgへ低下し、腹水穿刺の頻度も週に1度程度へ改善したが難治性腹水からの離脱には至らなかった。しかし、A-Pシャント塞栓術後、門脈本幹血流は求肝性となり肝性脳症が制御可能となった。そこでA-Pシャント塞栓術の38日後にTIPSを行った。TIPSにより、門脈大循環圧較差は19mmHgから6mmHgへ低下し、腹水は著明に改善し、腹水穿刺・利尿剤ともに中止可能となった。その後肝機能は徐々に改善し、TIPS 8ヵ月後には腹水は完全消失し、Child-Pughスコアは6点まで改善した。76歳時にDAA(LDV/SOF)を導入したところウイルスは持続陰性化し、78歳となった現在でも健在である。(著者抄録)

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開催年月日： 2019年5月

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開催年月日： 2019年4月

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開催年月日： 2019年4月

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開催年月日： 2019年4月

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開催年月日： 2019年4月

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開催年月日： 2019年3月

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開催年月日： 2019年3月

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開催年月日： 2019年2月

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開催年月日： 2019年

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開催年月日： 2019年

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開催年月日： 2019年

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開催年月日： 2018年11月

記述言語：日本語  

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開催年月日： 2018年11月

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開催年月日： 2018年9月

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開催年月日： 2018年9月

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開催年月日： 2018年9月

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開催年月日： 2018年9月

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開催年月日： 2018年9月

記述言語：日本語  

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開催年月日： 2018年9月

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開催年月日： 2018年8月

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開催年月日： 2018年8月

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開催年月日： 2018年4月

記述言語：日本語  

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開催年月日： 2018年4月

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開催年月日： 2018年3月

記述言語：日本語  

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開催年月日： 2018年

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開催年月日： 2018年

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開催年月日： 2017年11月

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開催年月日： 2017年8月

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開催年月日： 2017年8月

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開催年月日： 2017年8月

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開催年月日： 2017年4月

記述言語：日本語  

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開催年月日： 2017年4月

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開催年月日： 2017年3月

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開催年月日： 2016年8月

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開催年月日： 2016年8月

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開催年月日： 2016年8月

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開催年月日： 2016年8月

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開催年月日： 2015年8月

記述言語：日本語  

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開催年月日： 2014年2月

記述言語：日本語  

40歳男。心窩部痛を主訴に近医を受診、白色便とトランスアミナーゼの上昇から急性肝炎が疑われ、著者らの施設へ紹介となった。所見では眼球結膜と全身皮膚に著明な黄染がみられ、両側顎下腺部には腫大が認められた。また、胆道系優位の酵素異常と高ビリルビン血症、血清IgG値の上昇があったものの、ANAやAMAは陰性、膵・胆道系の腫瘍マーカーも高値を認めるもHBs抗原、HCV抗体は陰性であった。一方、腹部超音波では肝内胆管は拡張し、中部胆管には全周性壁肥厚が認められた。更にMRCPでは中部胆管に約1.5cmの内腔狭窄が認められ、狭窄部より上流の総胆管と肝内胆管は拡張していたが肝内胆管の壁不整は認められなかった。以上より、本症例は中部胆管狭窄による閉塞性黄疸と診断されたが、IgG4関連硬化性胆管炎(IgG4-SC)の可能性を考慮しドレナージ治療を兼ねたERCPが行われた。一方、顎下腺腫大に関しては、超音波で両側の顎下腺は腫大し低エコーを呈しており、小唾液腺を有する口唇の生検ではIgG4陽性の形質細胞浸潤が認められ、IgG4-SC+IgG4関連顎下腺炎であった。以後、これらを踏まえ、ENBDチューブによる減黄と同時にPSLによる治療を行なった結果、中部胆管の狭窄は改善し、あわせて両顎下腺腫大の縮小、腫瘍マーカーの正常化とともに病態も改善した。尚、外来にてPSLは継続されたが再燃は認めず、画像での悪性所見も認められていない。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01937&link_issn=&doc_id=20140219090016&doc_link_id=10.19020%2FJ01937.2014142465&url=https%3A%2F%2Fdoi.org%2F10.19020%2FJ01937.2014142465&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

開催年月日： 2013年11月

記述言語：日本語  

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開催年月日： 2013年9月

記述言語：日本語  

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開催年月日： 2013年6月

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開催年月日： 2013年2月

記述言語：日本語  

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開催年月日： 2012年10月

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開催年月日： 2012年10月

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開催年月日： 2012年10月

記述言語：日本語  

53歳男。アルコール依存症に対し精神科クリニックにてシアナミドを開始し、治療は順調であったが、AST、ALTのトランスアミナーゼの軽度上昇を認めたため紹介となった。腹部超音波では、アルコール性肝機能障害所見であった。肝生検では、門脈域に中等度の単核細胞浸潤、門脈域の線維性拡大および削り取り壊死(Piecemeal necrosis)を認めたものの実質への線維延長はなかった。病理組織所見は、肝細胞質内に内部が均一で境界明瞭な封入体様構造物が蓄積された特異な像を呈し、HE染色で淡いピンク色に染色され、PAS染色で強く濃染され、GGIと呼ばれるシアナミドによる薬剤性肝障害による特徴的所見であった。シアナミドを中止し、代替薬としてジスルフィラムを開始し継続中である。トランスアミナーゼおよびALTは2〜3ヵ月を経て軽快傾向にあるが依然として高値である。

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開催年月日： 2012年9月

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開催年月日： 2012年6月

記述言語：日本語  

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開催年月日： 2012年6月

記述言語：日本語  

50歳男。健康診断で肝胆道系酵素異常を指摘され紹介となり、高IgG血症、抗核抗体(ANA)陽性、その後、ALP、γGTPの上昇により精査、病勢評価目的に入院となった。体幹と上肢を中心に痛みや痒みのない淡い紅斑様皮疹を認め、両鼠径部に数ミリ大の無痛性のリンパ節を触知したが、陰部に異常所見は認めなかった。胆道系優位の酵素異常、高γグロブリン血症を認めたが、肝炎ウィルスマーカーはB、Cとも陰性であった。感染症検査では、梅毒定性反応が強陽性、定量検査では血清梅毒反応が強陽性、HIV抗体は陰性で、第II期梅毒と診断した。また、超音波で肝および辺縁がやや腫大し、第II期梅毒に伴う肝機能障害が示唆された。経皮的肝生検では、末梢門脈域は浮腫状で軽度炎症性細胞浸潤、他の門脈域に軽度の細胆管増生、中心静脈の一側に壊死性炎症細胞浸潤巣、小葉内中間体にクッパー細胞または組織球の集簇像を認め、鏡顕上Tpは認められないが梅毒性肝炎と判断した。アモキシシリン(AMPC)による駆梅療法開始時より肝機能異常は速やかに軽快し、治療終了後も肝炎の再燃は認めない。

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開催年月日： 2012年6月

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開催年月日： 2012年2月

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開催年月日： 2011年11月

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開催年月日： 2011年11月

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開催年月日： 2011年10月

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開催年月日： 2010年8月

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開催年月日： 2010年7月

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開催年月日： 2010年5月

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開催年月日： 2009年12月

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開催年月日： 2005年10月

記述言語：日本語  

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開催年月日： 2005年2月

記述言語：日本語  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J04260&link_issn=&doc_id=20050601330001&doc_link_id=10.1272%2Fmanms.1.2&url=https%3A%2F%2Fdoi.org%2F10.1272%2Fmanms.1.2&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif