Use of the Serum Wisteria floribunda Agglutinin-Positive Mac2 Binding Protein as a Marker of Gastroesophageal Varices and Liver-Related Events in Chronic Hepatitis C Patients

Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 consecutive chronic hepatitis C patients. The correlation between the grades of GEV and fibrosis markers and the subsequent occurrence of liver-related and fibrosis markers were examined. Results: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+–M2BP) levels increased according to the grade of GEV (3.4 (0.2–18.6) for no GEV, 7.9 (1.8–20.0) for small GEV, and 11.4 (4.0–20.0) for large GEV; p < 0.001). The diagnostic accuracy of the WFA+–M2BP was superior compared to other serum fibrosis markers, and WFA+–M2BP was an independent predictor of GEV in the multivariate analysis. Furthermore, the cumulative incidence of liver-related events at one year was 2.3% in patients with WFA+–M2BP levels ≤ 7.0 and 37.5% in patients with WFA+–M2BP levels > 7.0 (p < 0.001). WFA+–M2BP > 7.0 was a significant predictive factor for liver-related events (Hazard ratio 6.7, p = 0.004) independent of Child–Pughclass. Conclusions: WFA+–M2BP could be used to estimate the presence and grade of GEV and is linked to liver-related events in chronic hepatitis C patients

Impact of pre-sarcopenia in sorafenib treatment for advanced hepatocellular carcinoma.

BACKGROUND:The present study aimed to investigate the impact of pre-sarcopenia on the prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS:We enrolled 214 patients (71 ± 10 years old; 166 men and 48 women; 90% Child-Pugh grade A and 10% Child-Pugh grade B) treated with sorafenib in our hospital from July 2009 to August 2016. The muscle volume was measured from CT images just before sorafenib administration using software (SliceOmatic). Skeletal muscle mass index was calculated, and the presence of pre-sarcopenia was judged according to the standard (42 cm2/m2 for men and 38 cm2/m2 for women) proposed by the Japan Society of Hepatology. RESULTS:Pre-sarcopenia was found in 123 patients (57%). The overall survival (OS) in patients with pre-sarcopenia tended to be worse than in patients without pre-sarcopenia (median 252 vs. 284 days, respectively; p = 0.16). Multivariate Cox hazard analysis revealed a baseline serum albumin level of ≤3.5 g/dl [hazard ratio (HR) 1.9; p = 0.0006], a baseline alpha-fetoprotein(AFP) level of ≥100 ng/ml (HR 2.1; p = 0.002), presence of lesions in bilateral hepatic lobes (HR 1.7; p = 0.03), and presence of major portal vein invasion (HR 1.8; p = 0.01) to be independent prognostic factors. In the 68 patients who had three or more negative prognostic factors, the presence of pre-sarcopenia did not correlate with prognosis. Of the 146 patients who had two or less prognostic factors, OS was significantly worse in 84 patients (58%) with pre-sarcopenia than in 62 patients without pre-sarcopenia (median 417 vs. 562 days, respectively; p = 0.047), and Cox hazard analysis revealed pre-sarcopenia to be an important prognostic factor (HR 1.6; p = 0.047). CONCLUSION:In sorafenib treatment for advanced HCC, pre-sarcopenia is a significant prognostic factor in patients with two or less negative prognostic factors, and could be the target of intervention to improve prognosis

Distinctive magnetic resonance imaging findings of hepatocellular carcinoma after hepatitis C virus eradication with direct-acting antivirals

Aim: The aim of the present study was to evaluate the characteristics of the magnetic resonance imaging features of hepatocellular carcinoma (HCC) that developed early after the eradication of hepatitis C virus (HCV) by direct-acting antiviral (DAA) treatment.Methods: This study included 26 patients who achieved sustained viral response with DAA and developed HCC thereafter within one year (DAA-SVR HCC). The radiologic characteristics of these patients were evaluated by contrast-enhanced magnetic resonance imaging, including diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI). For comparison, 80 HCC patients with positive HCV RNA (HCV-positive HCC) were included. Among 42 patients where tumor biopsy was available, histological grade and radiologic findings were compared.Results: The rates of high intensity on DWI and T2WI were significantly higher in DAA-SVR HCC compared to HCV-positive HCC (DWI: 100% vs. 67.5%, P < 0.001; T2WI: 92.6% vs. 67.5%, P = 0.01). HCC with high intensity on DWI or T2WI was more likely to have moderately or poorly differentiated HCC compared to well-differentiated HCC (DWI: 69.7% vs. 30.3%, P = 0.02; T2WI: 66.7% vs. 27.3%, P = 0.03).Conclusion: High intensity on DWI and hyperintensity on T2WI were distinctive features of HCC that developed within one year after the end of DAA treatment

Real-life experience of lusutrombopag for cirrhotic patients with low platelet counts being prepared for invasive procedures.

Background and aimsThe present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts.MethodsWe studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed.ResultsIn 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts 30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index ConclusionsLusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions

Longitudinal association of magnetic resonance elastography‐associated liver stiffness with complications and mortality

BackgroundMagnetic resonance elastography (MRE) has the highest diagnostic accuracy for liver fibrosis; however, the association between MRE-associated liver stiffness and the development of hepatic and extrahepatic complications as well as mortality remains unclear.AimIn this study, we investigated the longitudinal association between MRE-associated liver stiffness and complications and mortality.MethodsThis retrospective study included 2373 consecutive patients with chronic liver disease. All patients received standard of care and the development of complications was assessed every 1-6 months.ResultsNewly diagnosed hepatocellular carcinoma (HCC), decompensation, major adverse cardiovascular events (MACE), extrahepatic cancer and death were observed in 99, 117, 73, 77 and 170 patients respectively. In multivariable analysis, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 1.28 (1.2-1.4), 1.34 (1.3-1.4), 0.96 (0.9-1.1), 1.00 (0.9-1.1) and 1.17 (1.1-1.2), respectively, with each 1-kPa increase in liver stiffness. Similarly, the aHR (95% CI) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 4.20 (2.2-8.2), 67.5 (9.2-492), 0.83 (0.4-1.7), 0.90 (0.5-1.7) and 2.90 (1.6-5.4), respectively, in patients with cirrhosis (>4.7 kPa) compared to those with minimal fibrosis (<3 kPa).ConclusionsIncreased MRE-associated liver stiffness was associated with increased risk for HCC, decompensation and mortality in a dose-dependent fashion but not with MACE or extrahepatic cancer, implicating a significant role for MRE in liver-related events and mortality; however, further studies are warranted to explore its role in MACE and extrahepatic cancer

Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup

Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1-16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7-8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population

Correction: Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0154558.]

Risk Difference of Liver-Related and Cardiovascular Events by Liver Fibrosis Status in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) has affected more than one-fourth of the global population, thus emerging as a worldwide health and economic burden.1 The common causes of death in patients with NAFLD include cardiovascular disease (CVD), decompensation, and hepatocellular carcinoma (HCC). However, identifying the risk of these complications in patients with NAFLD remains an unmet need in clinical practice