Only a few studies have evaluated the long-term effects of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes mellitus (T2DM), and none have examined whether NAFLD improvement reduces T2DM ...incidence. We investigated the association between NAFLD improvement and T2DM incidence.
Between 2000 and 2012, 4,604 participants who underwent a health check twice with >10 years between were enrolled. Exclusion criteria were positive hepatitis B surface antigen, positive hepatitis C antibody, ethanol intake >20 g/day, and diabetes. The 3,074 eligible participants were divided into an NAFLD group (n = 728) and a non-NAFLD group (n = 2,346) according to ultrasonography-detected fatty liver. The NAFLD group was categorized into an improved group (n = 110) and a sustained NAFLD group (n = 618) based on fatty liver disappearance at the second visit. Incident T2DM odds ratios (ORs) were estimated by logistic regression models adjusted for age, sex, BMI, impaired fasting glucose, family history of diabetes, dyslipidemia, hypertension, and physical exercise.
T2DM occurred in 117 participants (16.1%) in the NAFLD group and 72 (3.1%) in the non-NAFLD group. NAFLD at baseline was associated with T2DM incidence (multivariate OR 2.37 95% CI 1.60-3.52). T2DM occurred in 7 participants (6.4%) in the improved group and in 110 (17.8%) in the sustained NAFLD group. NAFLD improvement was associated with reduced T2DM incidence (multivariate OR 0.27 95% CI 0.12-0.61).
NAFLD improvement is associated with T2DM incidence reduction.
Aim
Lenvatinib (LEN) has recently become available as a first‐line tyrosine‐kinase inhibitor (TKI) for unresectable hepatocellular carcinoma (u‐HCC). In patients who showed intolerability or failure ...in other TKI treatments, alternative treatment options are needed. This retrospective study evaluated the therapeutic potential of LEN in clinical practice.
Methods
We enrolled 57 u‐HCC patients treated with LEN from March to June 2018. Lenvatinib was given orally to patients weighing <60 kg at 8 mg/day and at 12 mg/day to those ≥60 kg. Following the exclusion of patients whose initial LEN dose was reduced, 49 patients were evaluated in regard to their characteristics and early therapeutic response using modified Response Evaluation Criteria in Solid Tumors for findings of follow‐up computed tomography (CT)/magnetic resonance imaging (MRI) examinations at 4 weeks after introducing LEN.
Results
The average patient age was 72.4 ± 9.3 years and 38 (77.6%) were men. The LEN dose was 8 and 12 mg in 32 and 17 patients, respectively. Twenty‐nine (59.2%) had history of treatment with sorafenib and six of them (20.7%) with regorafenib. Of the 49 patients, 27 were evaluated using findings obtained by enhanced CT/MRI at 4 weeks after introducing LEN. Partial response was shown in 11, stable disease in 12, and progressive disease in four (overall response rate ORR, 40.7%; disease control rate DCR, 85.2%). The ORR and DCR of TKI‐naïve patients (n = 8) were 50.0% and 87.5%, respectively, whereas those of TKI‐experienced patients (n = 19) were 36.8% and 84.2%, respectively (P = 0.675 and P = 1.00, respectively).
Conclusion
Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments.
Background
Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving ...hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis.
Methods
The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction.
Results
The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (
p
= 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (
p
= 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups.
Conclusions
The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
Background/Aim: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging ...of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. Materials/Methods: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. Results: In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. Conclusion: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.
Background/Aim
Presently, there are no therapeutic options for unresectable hepatocellular carcinoma (u‐HCC) patients who are intolerant to sorafenib or regorafenib failure. There have been no ...reports with detailed clinical findings of lenvatinib (LEN), a newly developed first‐line tyrosine kinase inhibitor (TKI), obtained in real‐world practice. We aimed to elucidate the therapeutic efficacy of LEN.
Materials/Methods
From March to August 2018, 105 u‐HCC patients were treated with LEN. Following exclusion of those who started with a reduced LEN dose and/or had a short observation period (<2 weeks), 77 patients (72.0 ± 8.9 years, 59 males, 8 mg/12 mg = 49/28, Liver Cancer Study Group of Japan 6th LCSGJ‐TNM stage II/III/IVa/IVb = 8/28/4/37, and American Joint Committee on Cancer/Union for International Cancer Control 8th AJCC/UICC‐TNM stage IB:II:IIIA:IIIB:IVA:IVB = 2:27:6:5:9:28) were divided into two groups (TKI naïve n = 33 and TKI experienced n = 44, including 11 with regorafenib history). Therapeutic response was evaluated using mRECIST. Clinical data were retrospectively evaluated.
Results
There were significant differences in age (74.6 ± 11.2 vs 70.0 ± 5.9 years, P = 0.040), LCSGJ‐TNM (II:III:IVa:IVb = 8:12:1:12 vs 0:16:3:25, P = 0.006), and AJCC/UICC‐TNM (IB:II:IIIA:IIIB:IVA:IVB = 2:17:1:1:4:8 vs 0:10:5:4:5:20, P = 0.028), while hepatic reserve function, adverse event (AE) profiles, and progression‐free survival (89.7%/80.4% vs 90.5%/80.1%, P = 0.499) and overall survival (96.7%/96.7% vs 100%/92.3%, P = 0.769) after 4 and 12 weeks were not significantly different between the TKI‐naïve and TKI‐experienced groups. Overall response rate and disease control rate at 4 weeks (n = 52) were 38.5% and 80.8%, respectively, and 32.4% and 70.3%, respectively, at 12 weeks (n = 37). A significant decline in log10 AFP from the baseline to 4 weeks after introducing LEN was observed in patients with PR and SD (2.047 ± 1.148 vs 1.796 ± 1.179, P < 0.001).
Conclusion
Regardless of past TKI therapy, therapeutic response and AEs after introducing LEN were similar. LEN may be an important treatment for the present unmet need regarding TKI treatment against u‐HCC.
Presently, there are no therapeutic options for unresectable hepatocellular carcinoma (u‐HCC) patients who are intolerant to sorafenib or regorafenib failure, and there have been no reports with detailed clinical findings of lenvatinib (LEN), a newly developed first‐line tyrosine kinase inhibitor (TKI), obtained in real‐world practice. Regardless of past TKI therapy, therapeutic response and adverse events after introducing LEN were similar. LEN may be an important treatment for the present unmet need regarding TKI treatment for u‐HCC.
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.
Child‐Pugh score was not enough for evaluation of hepatic function in unresectable patients treated with lenvatinib. Good hepatic function (modified Albumin‐bilirubin grade 1/2a) is the best indication for lenvatinib. When lenvatinib is given to patients with lower BMI (<21.0 kg/m2), close attention is needed for decline of appetite, while a dose adjustment may be required soon in accordance with the condition in order to avoid a long period of interruption or stopping the drug, which can reduce therapeutic efficacy.
Epithelioid hemangioendothelioma is an exceedingly rare sarcoma often occurring as an indolent angiocentric vascular tumor at various anatomic sites. Few reports have evaluated large case series of ...epithelioid hemangioendothelioma.
We conducted a retrospective analysis of the clinical data of 42 consecutive patients with epithelioid hemangioendothelioma who were pathologically diagnosed between 1990 and 2014 at 13 Japanese tertiary hospitals. We analyzed their clinical characteristics, tumor features and prognostic factors.
The study included 22 men and 20 women, with a median age of 54 (range, 18-78) years. Pain was the most common symptom, occurring in 15 (68%) of the 22 symptomatic patients. The median maximum tumor diameter was 4.0 (range, 1.0-12.8) cm. The most commonly involved organs were the liver (81%), lungs (57%), and bones (12%). The overall survival rates were 79.5% at 1 year and 72.0% at 5 years. Substantially better survival was observed in asymptomatic patients than in symptomatic patients (P = 0.03), and better survival was also ovserved in patients with Ki-67 index ≤10% than in those with Ki-67 index > 10% (P = 0.04). By multivariate analysis, tumor size > 3.0 cm was associated with decreased survival (P = 0.049, hazard ratio 13.33).
This study showed the clinical characteristics of Japanese patients with epithelioid hemangioendothelioma. Tumor size > 3.0 cm is an independent indicator of a poor prognosis in epithelioid hemangioendothelioma. The presence of symptoms at the time of diagnosis and high Ki-67 index implied poor survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, ...small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV).
Methods
Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events.
Results
Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (
n
= 2), rash (
n
= 1), and HCC (
n
= 1); all of these achieved SVR12.
Conclusions
This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
Transarterial chemoembolization (TACE) is recommended for patients with intermediate‐stage (Barcelona Clinic Liver Cancer criteria B BCLC‐B) hepatocellular carcinoma (HCC). However, patients with ...BCLC‐B HCC can differ in background factors related to hepatic function, as well as tumor size and number. In the present study, we clarified the role of hepatic resection in patients with BCLC‐B HCC. A total of 489 BCLC‐B HCC patients with Child–Pugh class A disease initially treated with hepatic resection or TACE were included. After propensity score matching (n = 264), hepatic resection (hazard ratio HR, 0.56; 95% confidence interval CI, 0.35–0.91) was independently associated with survival in the multivariate analysis. We then divided patients into two groups based on the results of statistical analysis. There were 170 patients treated with resection and 319 with TACE. Child–Pugh score and number of tumors (cut‐off, three tumors) were independently associated with type of HCC treatment in the multivariate analysis. We then divided patients in Group A (Child–Pugh score of 5 and ≤3 tumors; n = 186) and Group B (Child–Pugh score of 6 or ≥4 tumors; n = 303). In Group A, cumulative survival was significantly higher in the hepatic resection group than in the TACE group (P = 0.014). In Cox proportional hazards models, hepatic resection (HR, 0.38; 95% CI, 0.23–0.64) was independently associated with survival in Group A patients. In Group B, treatment status was not associated with overall survival. Hepatic resection should be considered in patients with a Child–Pugh score of 5 and ≤3 tumors, despite having BCLC‐B HCC.
Patients with BCLC‐B HCC can differ in background factors related to hepatic function as well as tumor size and number. Hepatic resection should be considered as a radical treatment for patients with a Child‐Pugh score of 5 and ≤3 tumors, even though their HCC is staged as BCLC‐B.
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.
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