Usefulness of carotid duplex ultrasonography in predicting residual large-vessel occlusions after intravenous recombinant tissue plasminogen activator therapy in patients with acute ischemic stroke.

PURPOSE: Endovascular therapy (EVT) preceded by intravenous thrombolysis with recombinant tissue plasminogen activator (iv-rtPA) has been established as a standard treatment in patients with stroke caused by large-vessel occlusion (LVO). Primary stroke centers without EVT competence need to identify patients with residual LVO after iv-rtPA therapy and transport them to an EVT-capable facility. Carotid ultrasonography (CUS) is easily applicable at bed side and useful for detecting extra- and intracranial LVO. This study aimed to determine whether CUS findings at admission are useful to predict patients with residual LVO after iv-rtPA. METHODS: Patients scheduled to undergo iv-rtPA for acute cerebral infarction were registered. Before iv-rtPA, they underwent CUS, followed by CTA or MRA evaluation within 6 h after iv-rtPA. A model that can achieve 100% sensitivity for detecting residual LVO after iv-rtPA was studied. RESULTS: This study included 68 of 116 patients treated with iv-rtPA during the study period. National Institutes of Health Stroke Scale (NIHSS) score (cutoff value = 10) on arrival, hyperdense MCA sign on non-contrast CT, end-diastolic (ED) ratio on CUS, and eye deviation were significantly different between patients with residual LVO after iv-rtPA and those without. If any of these clinical features are positive in the screening test, residual LVO could be predicted with 100% sensitivity, 50% specificity, 64% positive predictive value, and 100% negative predictive value. CONCLUSION: Prediction of residual LVO with 100% sensitivity may be feasible by adding CUS to NIHSS score > 10, the presence of eye deviation, and hyperdense MCA sign.

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy.

PURPOSE: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0-5) in population #2. RESULTS: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. CONCLUSIONS: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

Health-Related Quality of Life Evaluation Using the Short Form-36 in Patients With Human T-Lymphotropic Virus Type 1-Associated Myelopathy.

Background: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is a neuroinflammatory disease, causing various neurological symptoms, including motor, sensory, and bladder and bowel dysfunctions. This study was designed to reveal the impact of HAM and related symptoms on health-related quality of life (HRQoL). Methods: We analyzed the Short Form-36 (SF-36) and clinical data of 538 patients with HAM registered in the HAM-net, a nationwide patient registry for HAM in Japan. HRQoL was evaluated using the SF-6D (a health state utility value calculated from the SF-36) and eight SF-36 subscales. A general liner model was used to estimate the impact of major HAM-related symptoms, including gait dysfunction, sensory disturbance in the legs (pain and numbness), urinary dysfunction, and constipation, on the SF-6D and SF-36 subscale scores. Results: The mean age and disease duration were 62.0 and 16.5 years, respectively. Of the patients, 73.2% needed walking aid; 42.7 and 67.1% had leg pain and numbness, respectively; 92.1% had urinary dysfunction; and 77.9% had constipation. The mean SF-6D score was 0.565, which was significantly lower than the national average (0.674 in the 60-69 years age group; p < 0.001), exceeding the minimal important difference (0.05-0.1). All the major symptoms were significantly associated with a decrease in the SF-6D score. The SF-36 subscale scores were significantly lower than the national standard of 50 (p ≤ 0.001), except for mental health (MH). Gait dysfunction was associated with lower scores in physical functioning (PF), limitations on role functioning because of physical health, bodily pain, general health perception (GH), vitality (VT), and social functioning; however, no association was observed between gait dysfunction and limitations on role functioning because of emotional problems and MH. Meanwhile, sensory disturbance in the legs was associated with a decrease in scores in all subscales. Urinary dysfunction was associated with worse PF, GH, VT, and MH. Constipation was associated only with PF. Conclusion: HRQoL of patients with HAM was worse than that of the general population and was associated with all major symptoms. Thus, patients should be comprehensively managed to achieve better HRQoL.

aMAP score prediction of hepatocellular carcinoma occurrence and incidence-free rate after a sustained virologic response in chronic hepatitis C.

AIMS: Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS: A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS: Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low-, medium-, and high-risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC-free following an SVR. CONCLUSION: The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR.

Utility of transoral motion-mode ultrasonography to detect tongue fasciculation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Increasing evidence suggests the utility of the submandibular approach for ultrasonography to detect tongue fasciculation in amyotrophic lateral sclerosis (ALS). We hypothesized that transoral motion-mode ultrasonography (TOMU) would be useful to detect tongue fasciculation in patients with ALS. METHODS: Patients with sporadic ALS showing clinically definite tongue fasciculation were enrolled, and the ultrasonography findings of patients' tongues on TOMU and ultrasonography by the conventional submandibular approach were analyzed. RESULTS: Six patients with clinically definite ALS were enrolled in this study. Although small, irregular muscle movements of 5 to 10 mm in amplitude and 0.1 to 0.2 second in duration were detected in all patients by TOMU, similar muscle movements were detected in only two of the six patients by the submandibular approach. DISCUSSION: TOMU appeared to be useful for detecting tongue fasciculation in ALS patients. Further study is needed to better determine its role as a diagnostic tool for ALS.

Effectiveness of Glecaprevir/Pibrentasvir for Hepatitis C: Real-World Experience and Clinical Features of Retreatment Cases.

Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1+2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.

Renal impairment is associated with increased risk of mortality in patients with cirrhosis: A retrospective cohort study.

Although renal impairment is a frequent complication in cirrhosis that is associated with a poor prognosis, little has been reported on the clinical significance of renal impairment in cirrhosis in Japan. This retrospective study assessed the impact of renal impairment on mortality in Japanese cirrhosis patients taking conventional diuretics.A total of 157 patients with cirrhosis receiving diuretic treatment were evaluated for the presence and status of renal impairment, defined as an increase in serum creatinine of ≥ 0.3 mg/dL or by ≥ 50%, and then classified according to the International Club of Ascites (ICA)-Acute Kidney Injury (AKI) staging system.Eighty of 157 (51%) patients fulfilled the criteria for renal impairment. Thirty-four (43%) patients had ICA-AKI stage 1, 32 (40%) stage 2, and 14 (18%) stage 3. Multivariate analysis revealed female gender (hazard ratio [HR] = 0.407, 95% confidence interval = 0.193-0.857; P = .018), ALT ≥35 IU/L (HR = 3.841, 95% confidence interval = 1.785-8.065; P = .001), and the presence of renal impairment (HR = 4.275, 95% confidence interval = 1.962-9.312; P < .001) as independent factors significantly increasing the risk of mortality. Cumulative survival rates increased significantly with ICA-AKI stage (log-rank test, P = .009).Renal impairment was a predictive marker of mortality in Japanese patients with cirrhosis. Stratification according to ICA-AKI criteria of kidney function impairment may be a good prognostic indicator of cirrhosis outcome.

Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct-acting antivirals.

Direct-acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC (+) (9.4%) and 759 HCC (-) (90.6%) patients and associations with treatment outcome. Male frequency was significantly higher in the HCC (+) group (60.8% vs 42.4%, P = 0.006). There were significant differences between the HCC (+) and HCC (-) groups for platelet count (115 vs 152 ×109 /L, P < 0.001), baseline alpha fetoprotein (AFP) (9.9 vs 4.5 ng/mL, P < 0.001) and the established fibrosis markers of FIB-4 index (4.7 vs 3.0, P < 0.001), AST-to-platelet ratio index (APRI) (1.1 vs 0.7, P = 0.009), M2BPGi (3.80 vs 1.78 COI, P < 0.001) and autotaxin (1.91 vs 1.50 mg/L, P < 0.001). The overall SVR rate was 94.7% and significantly lower in the HCC (+) group (87.3 vs 95.5%, P = 0.001). Multivariate analysis revealed that a history of HCC was independently associated with DAA treatment failure (odds ratio: 3.56, 95% confidence interval: 1.32-9.57, P = 0.01). In conclusion, patients with chronic HCV infection and prior HCC tended to exhibit more advanced disease progression at DAA commencement. HCC (+) status at the initiation of DAAs was significantly associated with adverse therapeutic outcomes. DAA treatment for HCV should therefore be started as early as possible, especially before complicating HCC.

Miglitol attenuates non-alcoholic steatohepatitis in diabetic patients.

AIM: Postprandial hyperglycemia is frequently accompanied by non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Although α-glucosidase inhibitors (αGIs) can slow glucose absorption from the intestine and suppress the surge of circulating glucose concentration after meals, it remains unclear whether αGIs are also beneficial for NASH. The aim of this prospective study was to examine the efficacy and safety of miglitol, a typical αGI, for NASH. METHODS: Seventeen patients with histologically confirmed NASH and hemoglobin A1c (HbA1c) >6.5% were treated with miglitol (150 mg/day) for 12 months. The changes in clinical parameters and liver histology were analyzed. RESULTS: All patients completed the 12-month miglitol treatment course with no severe adverse events. The treatment significantly decreased body mass index, serum alanine aminotransferase levels, and HbA1c (all P < 0.001). Post-treatment liver biopsy of 11 patients revealed significant improvements in steatosis (from 2.2 ± 0.6 to 1.5 ± 0.7, P = 0.001), lobular inflammation (from 1.8 ± 0.8 to 1.3 ± 0.5, P = 0.014), portal inflammation scores (from 0.6 ± 0.5 to 0.1 ± 0.3, P = 0.025), and NAFLD activity score (from 5.5 ± 1.5 to 3.9 ± 1.4, P = 0.012). Fibrosis and hepatocyte ballooning scores were unchanged. CONCLUSIONS: Miglitol appears to safely ameliorate NASH activity by attenuation of steatosis and lobular/portal inflammation. Appropriately powered controlled trials are warranted to validate our results.

Serum autotaxin is a useful liver fibrosis marker in patients with chronic hepatitis B virus infection.

AIM: Autotaxin (ATX) is a secreted enzyme that is considered to be associated with liver damage as well as fibrosis. This study assessed the ability of ATX to diagnose liver fibrosis in patients with chronic hepatitis B virus (HBV) infection. METHODS: Serum ATX levels were retrospectively evaluated in 101 treatment-naïve patients with HBV-related chronic hepatitis or cirrhosis, all of whom had undergone liver biopsy at our hospital. RESULTS: Serum ATX concentration increased significantly according to liver fibrosis stage in overall (r = 0.46, P < 0.0001), male (r = 0.55, P < 0.0001), and female (r = 0.52, P = 0.0006) patient groups. When analyzed by gender, serum ATX was one of the most reliable markers for all fibrosis stages compared with other tested non-invasive markers, which included hyaluronic acid, type IV collagen 7S, aspartate aminotransferase-to-platelet ratio index, and fibrosis index based on four factors, according to receiver operating characteristic curve analysis. CONCLUSION: Based on this histologically proven data, ATX represents a novel non-invasive biomarker for liver fibrosis in HBV-infected patients.

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection.

We report the first case of a patient with hepatitis C virus (HCV) infection and idiopathic thrombocytopenic purpura (ITP), who later developed acquired amegakaryocytic thrombocytopenia (AAMT), with autoantibodies to the thrombopoietin (TPO) receptor (c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

Cimetidine/lactulose therapy ameliorates erythropoietic protoporphyria-related liver injury.

A 21-year-old Japanese man was admitted to our hospital because of severe abdominal pain and jaundice. He had been suffering from abdominal pain attacks and liver dysfunction since 18 years of age. Liver histology showed amorphous brown deposits in the sinusoidal space and significant periportal fibrosis without apparent hepatitis. Increased protoporphyrin in serum and feces and ferrochelatase gene mutation confirmed the final diagnosis of erythropoietic protoporphyria (EPP). Since ursodeoxycholic acid (UDCA) intake and glucose infusion are insufficient to ameliorate jaundice and abdominal attacks, cimetidine and lactulose were added in order to suppress hepatic delta-aminolevulinic acid synthase and limit re-absorption of protoporphyrin, respectively. Afterwards, the jaundice, liver dysfunction and abdominal symptoms improved and UDCA, cimetidine, and lactulose administration was continued. A repeat biopsy at 1.5 years after adding cimetidine/lactulose revealed marked attenuation of periportal fibrosis and protoporphyrin deposits. As far as we know, this is the first demonstration of histological improvement of EPP-induced liver abnormalities due to persistent cimetidine/lactulose administration. These treatments may be useful for EPP-related liver injury.

Association of Serum Autotaxin Levels with Liver Fibrosis in Patients with Chronic Hepatitis C.

Metabolized by liver sinusoidal endothelial cells, autotaxin (ATX) is a secreted enzyme considered to be associated with liver damage. We sought to clarify the diagnostic ability of ATX for liver fibrosis in 593 biopsy-confirmed hepatitis C virus (HCV)-infected patients. The diagnostic accuracy of ATX was compared with clinical parameters and the established fibrosis biomarkers Wisteria floribunda agglutinin-positive Mac-2-binding protein, FIB-4 index, AST-to-platelet ratio, and Forn's index. Median ATX levels were consistently higher in female controls and patients than in their male counterparts (P < 0.01). Serum ATX concentration increased significantly according to liver fibrosis stage in overall and both genders (P < 0.001). The cutoff values of ATX for prediction of fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.8, 1.1, 1.3, and 1.7 mg/L, respectively, in male patients and 0.9, 1.7, 1.8, and 2.0 mg/L, respectively, in female patients. The area under the receiver operating characteristic curve for ATX to diagnose fibrosis of ≥F2 (0.861) in male patients was superior to those of FIB-4 index and Forn's index (P < 0.001), while that in female patients (0.801) was comparable with those of the other markers. ATX therefore represents a novel non-invasive biomarker for liver fibrosis in HCV-infected patients.

Association between endotoxemia and histological features of nonalcoholic fatty liver disease.

AIM: To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD). METHODS: One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS: Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P < 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological findings. CONCLUSION: LBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein may predict liver fibrosis and progression to hepatocellular carcinoma in patients with chronic hepatitis B virus infection.

AIM: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) is a reliable, non-invasive marker of liver fibrosis. This study assessed the ability of WFA+ -M2BP to diagnose liver fibrosis in patients with chronic hepatitis B virus (HBV) infection and evaluated WFA+ -M2BP as a predictor of hepatocellular carcinoma (HCC) development. METHODS: Serum WFA+ -M2BP values were retrospectively evaluated in 112 treatment-naïve patients with HBV-related chronic hepatitis and cirrhosis who had undergone liver biopsy at our hospital. RESULTS: Serum WFA+ -M2BP levels were significantly related with liver fibrosis (r = 0.3725, P = 0.001). Fibrosis stage F2, F3, and F4 had a cut-off index of 0.94, 1.26, and 1.26, respectively. For diagnosing F ≥ 2 fibrosis, the area under the receiver-operating characteristic curve for WFA+ -M2BP was 0.713 and comparable with those of other non-invasive fibrosis markers, such as hyaluronic acid, type IV collagen 7S, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, serum albumin, and platelet count. Multivariate analysis identified male, WFA+ -M2BP ≥0.71, alanine aminotransferase ≥80 IU/L, and platelet count <14.5 × 109 /L as independent risk factors for the development of HCC in patients with HBV infection. CONCLUSIONS: Serum WFA+ -M2BP values appear to be useful for assessing liver fibrosis stage and are independently associated with HCC development in patients with chronic HBV infection.

Clinicopathological characteristics of non-B non-C hepatocellular carcinoma without past hepatitis B virus infection.

AIM: Past hepatitis B virus (HBV) infection is considered a risk factor for hepatocarcinogenesis, but the clinicopathological characteristics of non-B non-C hepatocellular carcinoma (NBNC-HCC) excluding past HBV infection have not been investigated. This study aimed to clarify the clinicopathological features of strictly defined NBNC-HCC. METHODS: Among HCC patients who underwent surgical resection at our affiliated hospitals in Nagano prefecture, Japan, between 1996 and 2012, 77 were negative for serum anti-HBV core/surface antibodies in addition to HBV surface antigen and anti-hepatitis C virus antibody without signs of autoimmune liver disease, Wilson disease, or hemochromatosis. These patients were divided into the alcohol intake-positive group (ethanol intake >20 g/day, n = 31), non-alcoholic fatty liver group (steatosis >5% and ethanol intake <20 g/day, n = 30), and cryptogenic group (no ethanol intake or steatosis, n = 16). Preoperative clinical parameters, tumor and background liver pathology, and prognosis were analyzed. RESULTS: Advanced fibrosis and steatosis were detected in 64% and 60% of all patients, respectively. Approximately 85% of the alcohol intake-positive patients had advanced fibrosis. Non-alcoholic fatty liver HCC subjects had the highest body mass index and prevalence of diabetes, but 30-40% had none to mild fibrosis. The cryptogenic group of HCC patients had the lowest incidence of accompanying hepatic inflammation/fibrosis but the largest tumor size. Recurrence/survival rates were comparable among the groups. CONCLUSIONS: Liver fibrosis and steatosis are risk factors of HCC regardless of past HBV infection and ethanol consumption. The present results also indicate the possibility of hepatocarcinogenesis independent of hepatic steatosis, inflammation and fibrosis, ethanol intake, and past HBV infection.

Association between serum soluble CD14 and IL-8 levels and clinical outcome in primary biliary cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often leads to liver decompensation and liver failure. Although the biochemical response to ursodeoxycholic acid (UDCA) can predict disease outcome in PBC, few biomarkers have been identified as prognostic tools applicable prior to UDCA treatment. We therefore sought to identify such indicators of long-term outcome in PBC in the Japanese population. METHODS: The prebiopsy serum samples and subsequent clinical data of 136 patients with PBC treated with UDCA were analysed over a median follow-up period of 8.8 years. Serum levels of biomarkers related to microbial translocation (sCD14, EndoCAb and I-FABP) were measured along with those of 33 cytokines and chemokines and additional auto-antibodies. Associations between the tested parameters and the clinical outcomes of liver decompensation and liver-related death/liver transplantation were evaluated using the Cox proportional hazards model with stepwise methods and Kaplan-Meier analysis. RESULTS: Elevated levels of serum IL-8, and sCD14 before UDCA therapy were significantly associated with both liver decompensation and liver-related death/liver transplantation. In multivariate analyses, IL-8≥46.5 pg/mL or sCD14≥2.0 µg/mL at enrolment demonstrated the same results. Kaplan-Meier analysis also revealed IL-8 and sCD14 to be significantly associated with a poor outcome. sCD14 was significantly correlated with IL-8. EndoCAb and I-FABP were not related to disease outcome. CONCLUSIONS: Serum IL-8 and sCD14 levels before UDCA therapy represent noninvasive surrogate markers of prognosis in patients with PBC.

Liver stiffness-spleen size-to-platelet ratio risk score detects esophageal varices in chronic liver disease.

BACKGROUND: Noninvasive markers are needed to identify esophageal varices (EV) in patients with chronic liver disease (CLD). Recently, liver stiffness (LS)-spleen size-to-platelet ratio risk score (LSPS) has been shown to predict EV in patients with chronic hepatitis C. The aim of this study was to validate the clinical value of LSPS for EV detection and identification of high risk EV in Japanese patients with CLD. METHODS: A total of 230 patients with CLD who had undergone endoscopy, LS measurement, and ultrasonography between 2013 and 2015 were enrolled. The relationships between clinical data and LSPS were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, and platelet-to-spleen ratio), along with platelet count, spleen size, and LS. Diagnostic and prognostic abilities were assessed by the area under the receiver operating characteristic curve (AUC) and multivariate logistic regression. RESULTS: LSPS correlated significantly with EV grade (P < 0.001) and was superior to the other noninvasive indices for determination of EV and high risk EV. Furthermore, LSPS was independently associated with the presence of EV (P < 0.001) and elevated EV risk (P = 0.013) by multivariate logistic regression analysis. The optimal cutoff values of LSPS for EV and high risk EV were 1.1 and 2.2, respectively, at which AUC, negative predictive value, and accuracy were 0.821 [95 % confidence interval (CI) 0.743-0.899], 91.9, and 84.3 % and 0.859 (95 % CI 0.736-0.981), 95.5, and 76.9 %, respectively. CONCLUSIONS: LSPS represents a useful, noninvasive, accurate method to detect EV and a high EV risk in Japanese patients with CLD.

Controlled attenuation parameter is correlated with actual hepatic fat content in patients with non-alcoholic fatty liver disease with none-to-mild obesity and liver fibrosis.

AIM: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. METHODS: Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(®) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. RESULTS: CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m(2) (r = 0.579, P < 0.0001), especially less than 25 kg/m(2) (r = 0.708, P < 0.01), but the meaningful correlation disappeared in the patients with BMI of 28 kg/m(2) or more. In the patients with BMI of less than 28 kg/m(2) , CAP quantitativeness was affected by the presence of stage 2-4 fibrosis, but not the presence of hepatocyte ballooning and severity of lobular inflammation. CONCLUSION: CAP may be a promising tool for quantifying hepatic fat content in NAFLD patients with none-to-mild obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28 kg/m(2) or significant hepatic fibrosis.