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The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR.Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12).5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common.LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

Background Hepatitis B virus (HBV) infection is strongly associated with hepatocellular carcinoma due to the main pathogenic X protein of HBV (HBx). Whether HBV infection and the HBx protein could result in macular degeneration (MD) is not known. The aim of this study is to assess the association and underlying mechanisms between HBV infection and MD. Methods The National Health Research Institutes in Taiwan built a large database, the National Health Insurance Research Database (NHIRD), which includes the claims data from the Taiwan National Health Insurance (NHI) program. The Taiwan NHI is a single-payer, compulsory health insurance program for Taiwan citizens. The data for the present study were derived from the Longitudinal Health Insurance Database, which contains the claims data of 1 million insured people within the NHIRD, including beneficiary registration, inpatient and outpatient files, drug use, and other medical services. In this study, we first investigated the association of HBV infection and the risk of MD by a population-based cohorts study enrolling 39,796 HBV-infected patients and 159,184 non-HBV-infected patients. Results After adjustment of age, sex, and comorbidities, the risk of MD was significantly higher in the HBV-infected cohort than in the non-HBV-infected cohort (adjusted HR = 1.31; 95% CI = 1.17–1.46). In vitro, we provided evidence to demonstrate that overexpression of HBx in the human retinal pigment epithelial (RPE) cell line, ARPE19, significantly reduced cell viability and clonogenic survival upon UV and blue light irradiation. By gene microarray analysis, we further showed that almost all genes in DNA repair pathways including base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination were significantly down-regulated in the UV-induced cell death of HBx-transfected ARPE19 cells. Conclusions The HBx protein may sensitize RPE cells to UV and blue light irradiation and increase the risk of HBV-infection-associated MD through down-regulation of multiple DNA repair pathways. Electronic supplementary material The online version of this article (10.1186/s12967-018-1594-4) contains supplementary material, which is available to authorized users.

Etifoxine, an 18 kDa translocator protein (TSPO) agonist for the treatment of anxiety disorders in clinic, may be able to cause acute liver injury or cytolytic hepatitis. TSPO has been demonstrated to participate in inflammatory responses in infective diseases as well as to modulate glucose and lipid homeostasis. Hepatitis C virus (HCV) infection disrupts glucose and lipid homoeostasis, leading to insulin resistance (IR). Whether TSPO affects the HCV-induced IR remains unclear. Here, we found that the administration of etifoxine increased the TSPO protein expression and recovered the HCV-mediated lower mitochondrial membrane potential (MMP) without affecting HCV infection. Moreover, etifoxine reversed the HCV-induced lipid accumulation by modulating the expressions of sterol regulatory element-binding protein-1 and apolipoprotein J. On the other hand, in infected cells pretreated with etifoxine, the insulin-mediated insulin receptor substrate-1/Akt signals, forkhead box protein O1 translocation, and glucose uptake were blocked. Taken together, our results pointed out that etifoxine relieved the HCV-retarded MMP and reduced the lipid accumulation but deteriorated the HCV-induced IR by interfering with insulin signal molecules.

Background Bipolar disorder (BD), a type of psychiatric mood disorder, is manifested by chronic and recurrent mood fluctuations. This study aims to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for BD. Methods A total of 48,215 patients with newly diagnosed viral hepatitis from 2000 to 2010 were identified and frequency-matched with 192,860 people without hepatitis. Both groups were followed until diagnosis with BD, withdrawal from the national health insurance program, or the end of 2011. Patients with viral hepatitis were grouped into 3 cohorts: HBV infection, HCV infection, and HBV/HCV coinfection. The association between viral hepatitis and BD were examined using Cox proportional hazards regression models. Results The incidence of BD was higher in HBV/HCV coinfection than in the control group, with an adjusted hazard ratio of 2.16 (95% confidence interval 1.06–4.41) when adjusted for sex, age, and comorbidity. After further adjustment, we noted that an age more than 65 years and female may be associated with an increased risk of BD in patients with chronic hepatitis B and C. Conclusion Viral hepatitis may be associated with increased risk of subsequent BD. Electronic supplementary material The online version of this article (10.1186/s12967-018-1542-3) contains supplementary material, which is available to authorized users.

The risk of peptic ulcer disease (PUD) among patients with depression has raised concern. This study determined the association between depression and the subsequent development of PUD using claims data. Patients newly diagnosed with depression in 2000 to 2010 were identified as depression cohort from the Taiwan National Health Insurance Research Database. The comparison cohort was randomly selected from subjects without depression, frequency matched by age and gender and diagnosis date, with a size 2-fold of the size of the depression cohort. The incidence of PUD was evaluated for both cohorts by the end of 2011. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of PUD using the Cox proportional hazards regression model. The depression cohort consisted of 23,536 subjects (129,751 person-years), and the comparison cohort consisted of 47,069 subjects (285,592 person-years). The incidence of PUD was 2-fold higher in the depression cohort than in the comparison cohort (33.2 vs 16.8 per 1000 person-years) with an age adjusted HR of 1.97 (95% CI = 1.89–2.06) or a multivariable adjusted HR of 1.35 (95% CI = 1.29–1.42). Depression might increase the risk of developing PUD. Prospective clinical studies of the relationship between depression and PUD are warranted.

Supplemental Digital Content is available in the text, Previous studies have reported that patients with bipolar disorders (BDs) exhibit increased physical comorbidity and psychological distress. Studies have shown that schizophrenia and anxiety increase the risk of peptic ulcer diseases (PUDs). Therefore, we conducted this study to determine the association between these 2 diseases and examine the possible risk factors. We used patients diagnosed with BDs from the Taiwan National Health Insurance Research Database. A comparison cohort comprising patients without BDs was frequency matched by age, sex, and comorbidities, and the occurrence of PUDs was evaluated in both the cohorts. The BD and non-BD cohort consisted of 21,060 patients with BDs and 84,240 frequency-matched patients without BDs, respectively. The incidence of PUDs (hazard ratio, 1.51; 95% confidence interval, 1.43–1.59; P

Non-alcoholic steatohepatitis (NASH) is associated with hepatic fibrogenesis. Despite well-known cholesterol-lowering action of statins, their mechanisms against NASH-mediated fibrogenesis remain unclear. This study aimed at investigating the in vitro and in vivo anti-fibrotic properties of fluvastatin (Flu). Palmitate (PA)-induced changes in intracellular hydrogen peroxide levels in primary rat hepatocytes (PRHs) and human hepatoma cell line (HepG2) were quantified by dichlorofluorescein diacetate (DCF-DA) dye assay, whereas changes in expressions of NADPH oxidase gp91 phox subunit, α-smooth muscle actin (α-SMA), and NFκB p65 nuclear translocation were quantified with Western blotting. Quantitative real-time polymerase chain reaction (q-PCR) was used to investigate mRNA expressions of pro-inflammatory genes (ICAM-1, IL-6, TNF-α). Conditioned medium (CM) from PA-treated PRHs was applied to cultured rat hepatic stellate cell line, HSC-T6, with or without Flu-pretreatment for 2 h. Pro-fibrogenic gene expressions (COL1, TIMP-1, TGF-β1, α-SMA) and protein expression of α-SMA were analyzed. In vivo study using choline-deficient L-amino acid defined (CDAA) diet-induced rat NASH model was performed by randomly assigning Wistar rats (n = 28) to normal controls (n = 4), CDAA diet with vehicles, and CDAA diet with Flu (5 mg/kg or 10 mg/kg) (n = 8 each) through gavage for 4 or 8 weeks. Livers were harvested for histological, Western blot (α-SMA), and q-PCR analyses for expressions of pro-inflammatory (IL-6, iNOS, ICAM-1) and pro-fibrogenic (Col1, α-SMA, TIMP-1) genes. In vitro, Flu (1–20 μM) inhibited PA-induced free-radical production, gp91 phox expression, and NFκB p65 translocation in HepG2 and PRHs, while CM-induced α-SMA protein expression and pro-fibrogenic gene expressions in HSC-T6 were suppressed in Flu-pretreated cells compared to those without pretreatment. Moreover, α-SMA protein expression was significantly decreased in HSC-T6 cultured with CM from PA-Flu-treated PRHs compared to those cultured with CM from PA-treated PRHs. Flu also reduced steatosis and fibrosis scores, α-SMA protein expression, mRNA expression of pro-inflammatory and pro-fibrogenic genes in livers of CDAA rats. We demonstrated PA-induced HSC activation through paracrine effect of hepatocyte in vitro that was significantly suppressed by pre-treating HSC with Flu. In vivo, Flu alleviated steatosis-induced HSC activation and hepatic fibrogenesis through mitigating inflammation and oxidative stress, suggesting possible therapeutic role of Flu against NASH.

Rheumatoid arthritis (RA), a chronic, systemic inflammatory disorder, primarily affects joints. Several studies have indicated that early inflammation, cardiovascular disease, and depression in patients were associated with a considerably increased risk of dementia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for treating RA. NSAIDs facilitate alleviating RA-associated chronic pain, inflammation, and swelling. Therefore, we conducted this nationwide study for evaluating the association between the dementia risk and NSAID treatment in patients with RA. The RA cohort comprised patients aged 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database (RCIPD). Patients without RA were frequency matched with the RA cohort at a 1:4 ratio according to age, sex, and year of RA diagnosis. The relative risks of dementia were estimated using Cox proportional hazard models. The risk of dementia in the RA cohort was not significantly higher than that in the non-RA cohort (adjusted HR [hazard ratio] = 0.95, 95% confidence interval [CI] = 0.87–1.02). Regarding the duration of NSAID treatment, the risk of dementia was significantly lower when the RA cohort used NSAIDs for >2191 days (HR = 0.56, 95% CI = 0.45–0.68). A longer duration of NSAID treatment possibly reduces the risk of dementia. Additional studies are warranted for verifying the association of dementia risk with NSAID treatment in patients with RA.

Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression.We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models.The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58-1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer.Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IKKalpha expression and IkappaBalpha phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats receiving high dose of thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition, real-time PCR analysis indicated that hepatic mRNA expressions of TGF-beta1, alpha-SMA, collagen 1alpha2, TNF-alpha and iNOS genes were attenuated by thalidomide treatment. In conclusion, our results showed that thalidomide inhibited activation of HSC-T6 cells by TNF-alpha and ameliorated liver fibrosis in DMN-intoxicated rats.

Hepatic abscess caused by foreign body penetration of the alimentary tract is rare. We report a case of gastric antrum penetration due to a toothpick complicated by liver abscess formation. A 41-year-old man was admitted to our hospital with the chief complaint of upper abdominal pain for 2 mo. Esophagogastroduodenoscopy performed at a local clinic revealed a toothpick penetrating the gastric antrum. Computed tomography (CT) of the abdomen at our hospital revealed a gastric foreign body embedded in the posterior wall of gastric antrum with regional phlegmon over the lesser sac and adhesion to the pancreatic body without notable vascular injury, and a hepatic abscess seven cm in diameter over the left liver lobe. Endoscopic removal of the foreign body was successfully performed without complication. The liver abscess was treated with parenteral antibiotics without drainage. The patient's recovery was uneventful. Abdominal ultrasonography demonstrated complete resolution of the hepatic abscess six months after discharge. Relevant literature from the PubMed database was reviewed and the clinical presentations, diagnostic modalities, treatment strategies and outcomes of 88 reported cases were analyzed. The results showed that only 6 patients received conservative treatment with parenteral antibiotics, while the majority underwent either image-guided abscess drainage or laparotomy. Patients receiving abscess drainage via laparotomy had a significantly shorter length of hospitalization compared with those undergoing image-guided drainage. There was no significant difference in age between those who survived and those who died, however, the latter presented to hospitals in a more critical condition than the former. The overall mortality rate was 7.95%.

To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors.We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ≥ 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations.The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (β = 0.088, P0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R(2)0.95, P0.001).Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.