miRNAs circulating in the blood in a cell-free form have been acknowledged for their potential as readily accessible disease markers. Presently, histological examination is the golden standard for ...diagnosing and grading liver disease, therefore non-invasive options are desirable. Here, we investigated if miRNA expression profile in exosome rich fractionated serum could be useful for determining the disease parameters in patients with chronic hepatitis C (CHC).
Exosome rich fractionated RNA was extracted from the serum of 64 CHC and 24 controls with normal liver (NL). Extracted RNA was subjected to miRNA profiling by microarray and real-time qPCR analysis. The miRNA expression profiles from 4 chronic hepatitis B (CHB) and 12 non alcoholic steatohepatitis (NASH) patients were also established. The resulting miRNA expression was compared to the stage or grade of CHC determined by blood examination and histological inspection.
miRNAs implicated in chronic liver disease and inflammation showed expression profiles that differed from those in NL and varied among the types and grades of liver diseases. Using the expression patterns of nine miRNAs, we classified CHC and NL with 96.59% accuracy. Additionally, we could link miRNA expression pattern with liver fibrosis stage and grade of liver inflammation in CHC. In particular, the miRNA expression pattern for early fibrotic stage differed greatly from that observed in high inflammation grades.
We demonstrated that miRNA expression pattern in exosome rich fractionated serum shows a high potential as a biomarker for diagnosing the grade and stage of liver diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the ...early stage when curative treatments can be applied. HCC biomarkers, including
Lens culinaris
agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.
Methods
Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis.
Results
In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %.
Conclusions
Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.
Background
The relationship between the hepatitis B e antigen (HBeAg) seroconversion and the long-term natural history of liver disease has not been sufficiently investigated.
Methods
A total of 408 ...4352 person-year (PY) units patients with chronic hepatitis B virus (HBV) without antiviral therapy were enrolled. The study patients were divided into three groups, as follows: Group A (2666 PY units), seroconverted of HBeAg at age < 40; Group B (413 PY units), seroconverted of HBeAg at age ≥ 40; Group C (1273 PY units), persistently HBeAg positive. Yearly transition probabilities from each liver state chronic HBV infection, chronic hepatitis B, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) negativity were calculated using the Markov chain model.
Results
In the analysis of 1 year liver disease state transition probabilities, the liver states remained almost the same in Group A. In Groups B and C, each liver state tended to progress to a worse state. Assuming a chronic hepatitis B state at age 40 as the starting condition for simulation over the next 40 years, the chronic hepatitis B state accounted for approximately 60% of males aged ≥ 50 and approximately 40% of females aged ≥ 60 in Group A, and the HBsAg-negative state accounted for approximately 30–40% of males and females aged ≥ 60. In Groups B and C, the probabilities of patients with cirrhosis and HCC gradually increased with age.
Conclusions
Not only patients with persistent HBeAg positive, but also patients with delayed HBeAg seroconversion showed poor prognosis of liver-related natural history.
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
Atezolizumab plus bevacizumab showed superior progression-free and overall survival compared to sorafenib in the IMbrave150 trial. It would therefore be useful to compare the efficacy of ...lenvatinib and that of atezolizumab plus bevacizumab to determine if a benefit of one therapy against the other exists.
Objective
The aim of the present report was to apply a matching-adjusted indirect comparison (MAIC) to individual participant data (IPD) from patients treated with lenvatinib outside of randomized trials, to aggregate results derived from the IMbrave150 trial.
Patients and methods
Data from 455 patients who received lenvatinib as first-line systemic therapy for unresectable HCC represented the present IPD. Data inclusion were adapted to those reported in the IMbrave150 trial.
Results
Overall survival on atezolizumab plus bevacizumab proved to be superior to lenvatinib (log-rank: 0.001) with a hazard ratio of 0.59 (95% confidence interval 0.46–0.75). The number needed to treat ranged between seven in the first 12 months and five at the 15th month.
Conclusions
The present MAIC highlights that the combination of atezolizumab plus bevacizumab is superior to lenvatinib. However, updated data or sub-analyses of the IMbrave150 trial would provide more robust estimates for such a treatment comparison.
OBJECTIVE:Tenofovir alafenamide is a new prodrug of tenofovir that allows for the treatment of patients with hepatitis B virus (HBV) at a lower dose than with tenofovir disoproxil fumarate, due to ...the more efficient delivery of tenofovir to hepatocytes. In this study, we compared entecavir and tenofovir alafenamide in terms of their ability to reduce hepatitis B surface antigen (HBsAg) in the same group of patients with HBV infection.
METHODS:During March and June 2018, 129 patients who received entecavir were switched to tenofovir alafenamide. Every 3– 6 months for 1 year before and after switching to tenofovir alafenamide, all patients underwent measurements of HBsAg, hepatitis core-related antigen (HBcrAg), calcium (Ca), inorganic phosphorus, and estimated glomerular filtration rate (eGFR).
RESULTS:The percent decline rate during the entecavir and tenofovir alafenamide phases at 6 months were 2.38% (−3.57 to 0.00) and −3.57% (−7.14 to 0.00), respectively, and those at 12 months were 3.03% (−6.57 to 0.00) and −5.56% (−7.41 to −2.50), respectively. HBsAg levels were reduced significantly more during the tenofovir alafenamide phase than during the entecavir phase (P < 0.0001). There were no significant differences in the percent declines of HBcrAg, Ca, inorganic phosphorus, or eGFR during the entecavir and tenofovir alafenamide phases after 1 year.
CONCLUSION:tenofovir alafenamide significantly decreased HBsAg levels compared to entecavir.
Background and Aim
The fibrosis stage of non‐alcoholic fatty liver disease (NAFLD) is closely associated with long‐term prognosis, including liver‐related mortality. However, it is not yet clear ...whether noninvasive fibrosis markers can predict the incidence of non‐liver‐related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non‐liver‐related diseases, based on hepatic pathology and noninvasive fibrosis markers.
Methods
A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers.
Results
When these patients were categorized based on the severity of liver fibrosis as F0–2 (n = 196) and F3–4 (n = 50), the patients with F3–4 had significantly poorer prognosis in overall survival rates and all complications (P < 0.05). The fibrosis‐4 (FIB‐4) index was useful to predict overall survival and the incidence of hepatocellular carcinoma and liver cirrhosis (LC)‐related complications but not extrahepatic malignancies. Multiple logistic regression analyses revealed the following risk factors: total bilirubin ≥ 1.2 (hazard ratio HR 6.362, 95% confidence interval CI 1.393–29.052) and severe liver fibrosis (HR 6.512, 95% CI 1.433–29.592) for overall survival; liver fibrosis (F3–4) (HR 13.370, 95% CI 2.775–64.427) for hepatocellular carcinoma; FIB‐4 index (HR 26.560, 95% CI 3.320–212.494) for LC‐related complications, and liver inflammation (A2–3) (HR 4.214, 95% CI 1.354–13.116) for extrahepatic malignancies.
Conclusions
Severe liver fibrosis was associated not only with the hepatocarcinogenesis and LC‐related complications but also with extrahepatic malignancies. The FIB‐4 index was useful for predicting liver‐related diseases but had limitations in predicting extrahepatic malignancies.
Aim
Fatty liver is the most common liver disease. This study examined fatty liver and advanced fibrosis prevalence in a random sample of the Japanese general population.
Methods
A total of 6000 ...people randomly selected from two cities in Hiroshima Prefecture were invited to participate in this cross‐sectional study originally carried out for hepatitis virus screening. Ultrasonography and FibroScan (controlled attenuation parameter CAP and liver stiffness measurement LSM) were provided as additional tests.
Results
Of 6000 invited individuals, 1043 participated in hepatitis virus screening, of which 488 randomly selected individuals (median age, 56 years; interquartile range, 45–68 years; male participants, 49.8%) underwent ultrasonography, CAP, and LSM. Ultrasonography showed fatty liver in 24.6% and mild fatty liver in 32.8%. Controlled attenuation parameter showed severe steatosis in 27.5%, moderate steatosis in 12.5%, and mild steatosis in 11.1%. Overall, 62.1% were diagnosed with fatty liver based on ultrasonography or CAP. Nonalcoholic fatty liver disease (NAFLD) prevalence was 50.6%. Liver stiffness measurement found cirrhosis in 1.0% and severe fibrosis in 1.8%. Multivariate analysis of risk factors associated with ≥F2 or higher liver fibrosis showed that age ≥60 years and above (adjusted odds ratio AOR, 3.2; 95% confidence interval CI, 1.5–6.9; p = 0.0031), hepatitis C virus antibody positivity (AOR, 8.4; 95% CI, 1.0–68.4; p = 0.0467), and fatty liver (AOR, 2.3; 95% CI, 1.1–6.2; p = 0.0317) are independent risk factors.
Conclusions
In the general population, 62.1% had fatty liver, and NAFLD prevalence was twice as high as previously reported. Screening that is noninvasive, low‐cost, and does not require special techniques or equipment is needed to detect advanced liver fibrosis.
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