A single site study to investigate the current prevalence of anti-hepatitis C virus antibody among substance use disorder patients in Hiroshima-Insufficient testing and diagnosis.

AIMS: Hepatitis C virus (HCV) infection among drug users presents an important public health problem; however, little recognition and few approaches to address this issue in Japan. This study was conducted to investigate the current disease status by assessing anti-HCV antibody (Ab) seroprevalence among people who inject drugs (PWIDs) and people who use drugs (PWUDs) in Hiroshima, Japan. METHODS: This study was a psychiatric single-site chart review in patients with drug abuse problems in the Hiroshima region. The primary outcome was anti-HCV Ab prevalence among PWIDs who underwent anti-HCV Ab testing. The secondary outcomes included the prevalence of anti-HCV Ab among PWUDs who underwent anti-HCV Ab testing and the proportion of patients who underwent anti-HCV Ab examination. RESULTS: A total of 222 PWUD patients were enrolled. Among these, 16 patients (7.2%) had records of injection drug use (PWIDs). Eleven (68.8%) of the 16 PWIDs received anti-HCV Ab tests, and 4 (36.4%, 4/11) were anti-HCV Ab-positive. Among 222 PWUDs, 126 (56.8%) patients received anti-HCV Ab tests, and 57 of these patients (45.2%, 57/126) were anti-HCV Ab-positive. CONCLUSION: The prevalence of anti-HCV Ab among PWIDs and PWUDs who visited the study site was higher than the general population, which was 2.2% among hospitalized patients between May 2018 and November 2019. Considering the World Health Organization's (WHO) elimination goal and recent advances in HCV treatment, patients with drug abuse experience should be encouraged to take HCV tests and consult hepatologists for further investigations and treatment if they are positive for anti-HCV Ab.

Impact of labor analgesia on mode of delivery and neonatal outcomes in Japan: A retrospective cohort study.

Labor analgesia (LA) is associated with the potential hazard of high-risk delivery, such as cesarean section (CS) and instrumental vaginal delivery (IVD), and adverse neonatal outcomes such as neonatal asphyxia and respiratory distress. The objective was to examine the impact of LA on mode of delivery and neonatal outcomes and to counsel pregnant women about a potentially higher risk and allow them to decide LA or non-LA. This retrospective cohort study containing 5,184 pregnant women analyzed the association between LA and both mode of delivery and neonatal outcomes. LA increased the risk of IVD (Adjusted Odds Ratio [AOR] 3.25, 95% confidence interval [95%CI] 2.51-4.20) but decreased that of CS (AOR 0.52, 95%CI 0.44-0.60). Two factors (advanced maternal age [AOR 1.70, 95%CI 1.33-2.17] and primipara [AOR 4.72, 95%CI 3.30-6.75]) increased the risk of IVD. We should carefully consider the indication of LA for cases with these two factors since LA can increase the risk of IVD and adverse neonatal outcomes.

Prevalence of fatty liver and advanced fibrosis by ultrasonography and FibroScan in a general population random sample.

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.

Prevalence of Helicobacter pylori infection in the general population evaluated by a resident-register-based epidemiological study.

BACKGROUND: The current status of Helicobacter pylori infection in Japan has not been investigated. We evaluated the status of H. pylori infection in a Japanese general population using large-scale resident-register-based sampling. METHODS: All 6069 adults in a rural town and 6000 adults in two urban cities (3000 each), selected by register-based random sampling, were enrolled in our health check-up program. Antibody titers against Helicobacter pylori (cut-off value was 3 U/mL by Eiken E-plate) were evaluated, and subjects with a positive result were encouraged to undergo further examinations. RESULTS: A total of 1586 subjects participated in serum sampling. The overall prevalence of H. pylori infection was 40.0% (634/1586), and it increased with age both in rural and urban areas. Although the overall positive rate was higher in the rural area (49.4%) than in the urban areas (35.6 and 32.3%), there was no difference in H. pylori status of younger subjects between the two areas. Among 634 patients with a positive titer, 374 (59.0%) underwent further examinations including endoscopic examination, and 180/634 (28.4%) patients received eradication therapy. Gastric neoplasms (three adenocarcinomas and one adenoma) were found in our screening program. CONCLUSION: We clarified population-based random sampling data of H. pylori infection in a Japanese general population. In younger subjects, a decrease in the prevalence of H. pylori infection was confirmed both in rural and urban areas. This provides basic information for establishing a strategy to reduce gastric cancer deaths.

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study.

BACKGROUND: We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. METHODS: The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. RESULTS: NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5-60.3%: P = 0.008), hypertension (48.5-57.4%: P = 0.047), and hyperlipidemia (39.2-53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37-3.61: P = 0.026) and the median platelet count increased (15.1-17.9 × 104/µL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. CONCLUSIONS: The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Exacerbation of Portal Hypertensive Enteropathy after Endoscopic Injection Sclerotherapy for Esophageal Varices.

INTRODUCTION: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. METHODS: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. RESULTS: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. CONCLUSIONS: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.

Efficacy of Lusutrombopag for Thrombocytopenia in Patients with Chronic Liver Disease Scheduled to Undergo Invasive Procedures.

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×104/µL before lusutrombopag treatment to 7.2×104/µL before the invasive procedure (p<0.01), and patients undergoing 49 of the 53 (92%) treatment regimens succeeded in undergoing invasive procedures without needing platelet transfusions. In patients who received lusutrombopag treatment repeatedly, the median platelet count significantly increased following the second administration of lusutrombopag, and the effects of lusutrombopag were similar between the first and second administration. A multivariate analysis identified the absence of diabetes mellitus (odds ratio, 5.56 for presence; p=0.04) as a significant and independent predictor of a response to lusutrombopag. Conclusion Lusutrombopag treatment significantly increased platelet counts in patients with chronic liver disease, making it possible to receive invasive procedures. The treatment produced identical effects when it was repeated. The efficacy of lusutrombopag might be decreased in patients with diabetes mellitus.

Impact of viral eradication by direct-acting antivirals on the risk of hepatocellular carcinoma development, prognosis, and portal hypertension in hepatitis C virus-related compensated cirrhosis patients.

AIM: We analyzed the impact of hepatitis C virus eradication by direct-acting antiviral (DAA) therapy on the risk of development of hepatocellular carcinoma (HCC), prognosis, and portal hypertension in patients with liver cirrhosis. METHODS: The rate of HCC development and overall survival after achievement of sustained virological response (SVR) in 173 DAA-treated compensated cirrhosis patients without HCC history were retrospectively compared with that of 125 cirrhosis patients who achieved SVR by interferon (IFN)-based therapy or that of 85 cirrhosis patients who failed to respond to anti-HCV therapy. Changes in esophagogastric varices (EGV) and incidence of portosystemic encephalopathy were analyzed in 87 consecutive cirrhosis patients. RESULTS: The cumulative HCC development rates at 1, 3, and 5 years were 2%, 7%, and 7% for the DAA-SVR group, significantly lower than the 3%, 7%, and 18% for the non-SVR group (log-rank, P < 0.001). The cumulative overall survival rates were also significantly improved in the DAA-SVR group compared to the non-SVR group (log-rank, P < 0.001). These rates were similar between DAA-SVR and IFN-SVR groups (P = 0.121 and 0.261, respectively). Esophagogastric varices were aggravated, and portosystemic encephalopathy occurred in a subset of cirrhosis patients who achieved SVR by DAA therapy. These events were more frequent in patients with large feeding vessels for EGV and portosystemic shunts at the time of SVR. CONCLUSION: Achievement of SVR by DAA therapy reduces the risk of HCC development and prolongs survival, similar to theresults achieved with IFN-based therapy, but portal hypertension is not immediately improved in compensated liver cirrhosis patients.

Metabolomic/lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: A multicenter study.

AIM: Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological features of non-alcoholic steatohepatitis. We undertook this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning. METHODS: We enrolled 176 patients, of whom 132 were proven by liver biopsy as having non-alcoholic fatty liver disease (NAFLD) and classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review. We carried out gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography tandem mass spectrometry, and lipidomics with plasma. RESULTS: As correlates of hepatocellular ballooning, among the clinical parameters, serum type IV collagen 7S correlated most significantly with the ballooning grade (correlation coefficient [CC] = 0.463; P < 0.001). Among the metabolic/lipidomic markers, phosphatidylcholine (PC) (aa-44:8) correlated most significantly with the ballooning grade (CC = 0.394; P < 0.001). The area under the receiver operating characteristic curve of type IV collagen 7S, choline, and lysophosphatidylethanolamine (LPE) (e-18:2), was 0.846 (95% confidence interval, 0.772-0.919). CONCLUSIONS: Plasma levels of PC were positively correlated, and those of lysophosphatidylcholine and LPE were negatively correlated with hepatocellular ballooning in NAFLD patients. These non-invasive metabolic/lipidomic-based plasma tests might be useful to distinguish between cases of NAFLD with and without hepatocellular ballooning.

The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy.

BACKGROUND AND AIM: To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. METHODS: This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. RESULTS: The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups. CONCLUSIONS: We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN-free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.

Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial.

BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. METHODS: Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. RESULTS: Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. CONCLUSION: Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

Predictive Factors of Portal Hypertensive Enteropathy Exacerbation in Patients with Liver Cirrhosis: A Capsule Endoscopy Study.

BACKGROUND/AIMS: The clinical course and exacerbation of portal hypertensive enteropathy (PHE) are yet to be fully clarified. This study aimed to identify factors related to PHE exacerbation in patients with liver cirrhosis (LC). METHODS: Fifty patients with LC (33 male; mean age, 67 years), who underwent capsule endoscopy (CE) at the Hiroshima University Hospital between February 2009 and September 2015, were followed up for >6 months. Exacerbation is defined as the appearance of new lesions or worsening of existing lesions. The association between PHE exacerbation and the clinical factors was evaluated. RESULTS: PHE exacerbation was identified in 24 out of 50 (48%) of cases: erythema (14 cases); angioectasia (11 cases); erosions (9 cases); villous edema (8 cases); and esophageal varices (EVs; 6 cases). The following factors were significantly associated with PHE exacerbation: portosystemic shunts, EVs and portal hypertensive gastropathy (PHG) exacerbation. After therapy, CE findings among the 24 cases were as follows: villous edema (19 cases); erythema (17 cases); angioectasia (16 cases); erosions (12 cases); and EVs (9 cases), and no observable abnormalities in 2 cases. On multivariate analysis, exacerbation of EVs and PHG were independent predictors of PHE exacerbation. CONCLUSION: EVs and PHG exacerbation may predict PHE exacerbation in patients with LC.

Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring.

BACKGROUND AND AIMS: The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). MATERIALS AND METHODS: A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. RESULTS AND DISCUSSION: Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. CONCLUSION: The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH. METHODS: (1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE-TOFMS and LC-TOFMS. RESULTS: (1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(-) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(-) group (P < 0.05). Moreover, expression levels of SCD1 and ELOVL6 were significantly reduced. CONCLUSIONS: These results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy.

BACKGROUND: Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis. METHODS: Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis. RESULTS: Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P < 0.0001) as independent predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P < 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks. CONCLUSIONS: These results suggest that serum HMGB1 at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or HAIC.

Clinical outcomes of stereotactic body radiotherapy for elderly patients with hepatocellular carcinoma.

AIM: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma (HCC) in elderly patients. METHODS: From 2008 to 2015, 117 patients with HCC (≤3 nodules, ≤30 mm in diameter, Child-Pugh score ≤7, and no vascular or extracellular metastasis) were treated with SBRT at our hospital. We evaluated overall survival (OS), disease-free survival (DFS), local control, and adverse events. Patients were stratified according to age 75 years and older (elderly group, n = 54) and age younger than 75 years (young group, n = 63). RESULTS: The median OS in the elderly group was not significantly different from that in the young group (52 months vs. not reached, P = 0.27). The 1-, 2-, and 3-year OS rates were 96.2%, 77.6%, and 63.9%, respectively, in the elderly group, and 96.8%, 84.8%, and 67.7%, respectively, in the young group. The median DFS in the elderly group was significantly shorter than that in the young group (13 vs. 25 months, respectively; P = 0.03). The 1-, 2-, and 3-year DFS rates were 50.6%, 30.4%, and 26.6%, respectively, in the elderly group and 66.5%, 50.7%, and 45.3%, respectively, in the young group. The 3-year local tumor control rate in the elderly group was 98.1%, and that in the young group was 98.4% (P = 0.83). There was no difference between groups in the incidence of any adverse events. CONCLUSIONS: Stereotactic body radiotherapy can be effective and safe for the treatment of HCC in elderly patients.

Efficacy and safety of edoxaban for treatment of portal vein thrombosis following danaparoid sodium in patients with liver cirrhosis.

AIM: To compare the efficacy and safety of edoxaban and warfarin for treatment of portal vein thrombosis (PVT) following danaparoid sodium in patients with liver cirrhosis. METHODS: Fifty cirrhotic patients with PVT treated initially for 2 weeks with danaparoid sodium were enrolled in this retrospective cohort study. Treatment was later switched to either edoxaban (n = 20) or warfarin (n = 30). We compared the efficacy and safety of edoxaban and warfarin for up to 6 months. The PVT volume was measured by dynamic computed tomography before treatment, at 2 weeks, and at 1, 3, and 6 months. RESULTS: There were no significant differences in the clinical characteristics of patients in the two groups. Treatment with edoxaban reduced the volume of PVT from 1.42 cm3 at 2 weeks to 0.42 cm3 at 6 months, and prevented exacerbation of PVT at 6 months after treatment with danaparoid sodium (P = 0.016). In contrast, treatment with warfarin resulted in increased PVT volume from 1.73 cm3 at 2 weeks to 2.85 cm3 at 6 months, despite the control of the international normalized ratio in 57% of the patients (P = 0.005). Multivariate regression analysis identified edoxaban therapy as the single significant and independent determinant of PVT reduction at 6 months (P = 0.0014, hazard ratio 6.400). Clinically significant gastrointestinal bleeding was encountered in 3 of 20 (15%) patients of the edoxaban group and 2 of 30 (7%) of the warfarin group (P = 0.335). CONCLUSION: Edoxaban following danaparoid sodium is an effective anticoagulant and could be potentially considered as one of the treatment options for PVT in cirrhotic patients.

Risk factors for exacerbation of gastroesophageal varices and portosystemic encephalopathy during treatment with nucleos(t)ide analogs for hepatitis B virus-related cirrhosis.

AIM: The aim of this study was to determine the risk factors for worsening of gastroesophageal varices (GEVs) and development of portosystemic encephalopathy in patients with hepatitis B virus (HBV)-related cirrhosis during nucleos(t)ide analog (NA) treatment. METHODS: One hundred and thirty-seven patients with HBV-related cirrhosis were enrolled in this retrospective cohort study. Findings of portal hemodynamics with computed tomography, liver function, and endoscopic examinations during NA treatment were assessed. RESULTS: Among 137 patients, feeding vessels for GEVs (left gastric vein, posterior gastric vein, and short gastric vein) were present in 56 (41%) patients, and extrahepatic portosystemic shunt (paraesophageal vein, paraumbilicul vein, and splenorenal shunt) were present in 36 (26%) patients at the start of NA treatment. Although NA treatment was successful, significant improvements were not observed in portosystemic collateral vessels 3 years after NA treatment and GEVs were exacerbated in 48 (35%) patients. The cumulative 5- and 10-year exacerbation rate of GEVs was 27% and 50%, respectively. By multivariate analysis, the existence of feeding vessels for GEVs at the start of NA treatment was the independent predictive factor for the exacerbation of GEVs (P < 0.001). Eight patients who had extrahepatic portosystemic shunt at the start of NA treatment developed portosystemic encephalopathy during follow-up. The 3- and 5-year incidence of that was 5% and 8%, respectively. CONCLUSIONS: The presence of portosystemic collateral vessels at the start of NA treatment increases the risk of GEVs worsening and development of portosystemic encephalopathy in patients with HBV-related cirrhosis, despite improvement of liver function and success in reducing viral loads with NA treatment.

Clinical significance of small-bowel villous edema in patients with liver cirrhosis: A capsule endoscopy study.

BACKGROUND AND AIM: The relationship between the presence of villous edema (VE) in portal hypertensive enteropathy and clinical factors remains unclear. The aim of this study was to reveal the clinical factors related to VE in patients with liver cirrhosis (LC), and investigate the clinical significance of VE. METHODS: Between February 2009 and September 2016, 363 consecutive patients with LC underwent capsule endoscopy for diagnosing portal hypertensive enteropathy at Hiroshima University Hospital. We evaluated the relationship between the presence of VE and patients' clinical characteristics, findings of esophagogastroduodenoscopy and computed tomography, and survival time. RESULTS: Villous edema was observed in 131 patients (36%), and severe lesions were found in 71 (20%). The presence of VE was significantly greater in patients with Child-Pugh classification B or C, esophageal varices, portal hypertensive gastropathy (PHG), ascites, portal vein thrombosis (PVT), and splenomegaly. In multivariate analysis, Child-Pugh class B or C, esophageal varices, PVT, and splenomegaly were significant predictive factors for the presence of VE. Severe VE was significantly greater in patients with Child-Pugh class B or C, serum albumin level ≤ 3.2 mg/dL, PHG, and PVT. In multivariate analysis, PHG, Child-Pugh class B or C, PVT, were significant predictive factors for severe VE. CONCLUSIONS: Clinical factors related to portal hypertension were significantly correlated with VE. In particular PVT was correlated with the appearance and exacerbation of VE. Periodic capsule endoscopy in LC patients may lead to early detection of portal hypertension and PVT.