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BACKGROUND The impact of diabetes on cirrhosis, its decompensation, and their time relationship in patients with chronic hepatitis B (CHB) remain unclear. METHODS We conducted a nationwide cohort study by using the Taiwanese National Health Insurance Research Database, which was comprised of data from >99% of the entire population. Among 1 million randomly sampled enrollees, 14 523 adult CHB patients were identified from 1997 to 2009. Diabetes was defined as newly diagnosed in CHB patients who were given the diagnosis in the years 1998-2001 but not in 1996-1997 and with physician visits of at least twice per year. The cohorts of CHB with newly diagnosed diabetes (n = 351) and without diabetes (n = 7886) were followed up from the diagnosis of diabetes and from 2000 in the patients without diabetes until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. RESULTS Kaplan-Meier survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR] = 3.43; 95% confidence interval [CI], 2.62-4.49; P < .001, log-rank test) and decompensated cirrhosis (RR = 4.11; 95% CI, 2.95-5.70; P < .001, log-rank test) among patients with newly developed diabetes compared with those without diabetes. After adjustment for age, sex, CHB treatment, hepatocellular carcinoma, and comorbidity index by Cox proportional hazards model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR] = 2.015; 95% CI, 1.393-2.915; P < .001) and its decompensation (HR = 1.792; 95% CI, 1.192-2.695; P = .005). CONCLUSIONS Patients with CHB who develop diabetes are at an increased risk of liver cirrhosis and its decompensation over time.

Colitis is a group of inflammatory and auto-immune disorders that affect the tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced animal models of colitis have indicated that nociceptive afferents or neuropeptides have differing effects on GI inflammation. However, the molecular mechanisms involved in visceral pain and the role of visceral sensory afferents involved in the modulation of colitis remains unclear. A previous study demonstrated that Runx1, a Runt domain transcription factor, is restricted to nociceptors. In these neurons, Runx1 regulates the expression of numerous ion channels and receptors, controlling the lamina-specific innervation patterns of nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit specific defects in thermal and neuropathic pain. To examine the function of Runx1 in visceral nociception, we employed double-transgenic mice (WntCre: Runx1(F/F)), in which the expression of Runx1 was specifically disrupted in the sensory neurons. To determine the role of Runx1 in visceral pain sensation, the WntCre: Runx1(F/F) mice and their control littermates (Runx1(F/F)) were treated using dextran sodium sulfate (DSS) to induce colitis. The results indicated that disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the phenotypes in murine DSS-induced colitis; (3) a differential effect on the production of pro- and anti-inflammatory cytokines in the colon tissues isolated from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and (4) alteration of the distribution of lymphocytes and mast cells in mucosa. These results show that the function of Runx1 in sensory afferents is vital for modulating visceral pain and the neuro-immune axis.

Background It remains unclear whether depression in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) during pegylated interferon-based therapy is associated with the virus, drug or ethnic background. We aimed to perform a prospective study to evaluate the clinical course of depression and its predictors in consecutive non-cirrhotic CHB and CHC patients of the same ethnicity receiving pegylated interferon-based therapy. Methods The occurrence and severity of depression were actively assessed by the Hamilton Depression Rating Scale before therapy and at weeks 2, 4, 6, 8, 10, 12 and every 4 weeks during treatment until the end of therapy. Extensive numbers of variables (repeated measurements, time variables and interactions between all variables) were included in generalized estimating equations to analyse the predictors of depression. Results A total of 158 consecutive patients (73 CHB and 85 CHC patients) were enrolled. Depression (Hamilton Depression Rating Scale ≥11) occurred in a biphasic pattern at treatment weeks 2-10 and weeks 16-36. Treatment weeks 12 predicts less depression, suggesting the predictability of the time variable during treatment on depression. Furthermore, CHC or pre-existing depression is an independent predictor of depression in these patients ( PConclusions Depression occurred in a biphasic pattern during pegylated interferon-based therapy and should be early and actively assessed, especially in patients with CHC or pre-existing depression.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in Western countries. The present study investigated the status and the risk factors for predicting mortality of ALD in Taiwan.We retrospective studied 100 consecutive in patients with ALD between 1992 and 2000. All patients had a history of alcohol consumption exceeding 80 g per day for at least 5 years.The study comprised 93 men and 7 women with a mean age of 45.4 years. The ALD included fatty liver (21%), alcoholic hepatitis (15%), alcoholic hepatitis superimposed on alcoholic cirrhosis (24%), and alcoholic cirrhosis (40%). Forty-four percent of patients had esophagogastric varices. Thirty-three percent of patients were mortality. The presence of esophagogastric varices was the only parameter identified by univariate and multivariate analyses and had a statistically significant association with increased mortality (OR: 8.603; 95% CI: 2.009-36.864; p = 0.004). The cumulative survival for ALD patients with varices was significantly lower than for patients without varices.The presence of esophagogastric varices had a statistically significant relationship with increased mortality. This study strongly implicates esophagogastric varices were a valuable poor prognostic factor with mortality. Upper gastrointestinal endoscopy is a simple clinical available tool for the assessment of the occurrence of varices to predict the disease severity and mortality in hospitalized patients with ALD.

Background Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine. Methods HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue mono-therapy for 44–48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20–24 weeks. Results HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 ±2.4 versus 7.7 ±1.4 versus 5.1 ±0.3 log10 copies/ml; P=0.06), treatment and follow-up durations (45.5 ±2.0 versus 49.7 ±5.6 versus 48.7 ±6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; PConclusions Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.

Human leukocyte antigen (HLA) class II molecules are associated with host immune responses against hepatitis B virus infection. Male gender is the apparent host factor when someone encounters with the severity of hepatitis. The aim of this study was to investigate the association of the most polymorphic HLA class II allele, human leukocyte antigen-DRB1, with the severity of hepatitis in male carriers of hepatitis B virus. In this prospective cohort study, a total of 204 carriers of hepatitis B virus (131 men and 73 women) who have been followed-up for more than 1 year at the outpatient clinic of a university hospital were collected consecutively. Fifty carriers of hepatitis B virus (group I) with alanine aminotransferase2x upper limit of normal (mean follow-up 83.6 months) were compared with 154 chronic hepatitis B patients (group II) with alanine aminotransferase/=2x upper limit of normal (mean follow-up 81.3 months). Alleles of HLA-DRB1 were typed by the polymerase chain reaction-sequence specific oligonucleotide probe hybridization and genotypes of hepatitis B virus by melting curve analysis. HLA-DRB1*1101 was found in 18% of group I versus 8% of group II in male carriers (OR 0.23, P = 0.020, after adjustment for age) and 4% versus 9.4% in female carriers (P = 0.094). In male carriers harboring DRB1*1101, the distribution of hepatitis B viral genotype was comparable between the two groups. HLA-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus.

To study whether interferon (IFN) α and ribavirin combination therapy has a beneficial effect for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, we enrolled 119 such patients in a randomized study. Fifty-nine patients received 5 million units of IFN-α2b daily for 4 weeks followed by 5 million units three times a week for 28 weeks, plus 1,200 mg ribavirin daily. Sixty patients received the same dosage of IFN plus placebo. They were followed up for 24 weeks posttreatment, and 105 patients (88%) completed the entire course of 56 weeks. By intention-to-treat analysis, the rate of combined response (serum hepatitis B virus [HBV] DNA

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease.Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five hours) for five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC. Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed.Six patients exhibited partial response to this form of HAIC (response rate=33%). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%, 28%, and 7%, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months, respectively. It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors.HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC.

To study the role of lamivudine in improving the efficiency of interferon for the treatment of mutant type chronic hepatitis B.Fifteen patients with mutant type chronic hepatitis B were prospectively studied. All patients had liver histology and serology to prove the diagnosis of chronic hepatitis B. Each patient received 4.5 million units of interferon alpha-2a thrice weekly and 100 mg of oral lamivudine daily for 24 weeks. Patients were observed and tested for blood chemistry every week for the initial 4 weeks and every 2 weeks thereafter during the treatment until 24 weeks. After the end of treatment, patients were followed up at 4-week intervals for an additional 6 months. Serum HBV DNA levels were tested using the liquid phase molecular hybridization assay. Those with non-detectable HBV DNA were also tested using the real-time polymerase chain reaction. One patient, who did not finish treatment due to depression, was excluded.At the end of treatment, 7 (50 %) patients had serum ALT levels within normal limits; 12 (86 %) patients had serum HBV DNA levels5 pg/mL using the liquid phase molecular hybridization assay, but only 8 (67%) were20 copies/dL using the real-time polymerase chain reaction. Six months after treatment, only two (14 %) patients had a sustained complete response to the combination therapy with serum ALT level35 iu/L and undetectable serum HBV DNA levels.These pilot data showed that lamivudine did not increase the efficacy of interferon in the treatment of mutant type chronic hepatitis B. The liquid phase molecular hybridization assay was not sensitive enough to detect the low HBV DNA levels during combined interferon and lamivudine therapy.

To study the changes of portal blood flow in congestive heart failure.We studied the congestion index (CI) and portal vein pulsatility index (PI) in patients with varied degrees of congestive heart failure using ultrasonic Doppler. Ten patients with (mean) right atrial pressure (RA)10 mmHg were classified as group 1 and the remaining 10 patients with RAor = 10 mmHg as group 2.There were no difference on cardiac index (HI, P=0.28), aortic pressure (AO, P=0.78), left ventricular end-diastolic pressure (LVED, P=0.06), (max)imum portal blood velocity (Vmax, P=0.17), (mean) portal blood velocity (Vmean, P=0.15) and portal blood flow volume (PBF, P=0.95) between the two groups. Group 2 patients had higher pulmonary wedge pressure (PW, 29.9+/-9.3 mmHg vs 14.6+/-7.3 mmHg, P=0.002), pulmonary arterial pressure (PA, 46.3+/-13.2 mmHg vs 25.0+/-8.2 mmHg, P=0.004), RA (17.5+/-5.7 mmHg vs 4.7+/-2.4 mmHg, P0.001), right ventricular end-diastolic pressure (RVED, 18.3+/-5.6 mmHg vs 6.4+/-2.7 mmHg, P0.001), CI (8.7+/-2.4 vs 5.8+/-1.2, P=0.03), and PI (87.8+/-32.3% vs 27.0+/-7.4%, P0.001) than Group 1. CI was correlated with PI (P0.001), PW (P0.001), PA (P0.001), RA (P=0.043), RVED (P=0.005), HI (P0.001), AO (P0.001), CO (P0.001), LVED (P0.001), Vmax (P0.001), Vmean (P0.001), cross-sectional area of the main portal vein (P0.001) and PBF (P0.001). CI could be as high as 8.3 in patients with RA10 mmHg and as low as 5.9 in those with RAor = 10 mmHg.Our data show that RI is a more significant indicator than CI in the clinical evaluation of high RAor = 10 mmHg, whereas CI is better than PI in the assessment of left heart function.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with tumor thrombosis of the portal vein tumor thrombosis

To study the change of portal blood flow for the prediction of the status of right-sided heart failure by using non-invasive way.We studied 20 patients with rheumatic and atherosclerotic heart diseases. All the patients had constant systemic blood pressure and body weight 1 week prior to the study. Cardiac index (CI), left ventricular end-diastolic pressure (LVEDP), mean aortic pressure (AOP), pulmonary wedge pressure (PWP), mean pulmonary arterial pressure (PAP), mean right atrial pressure (RAP), right ventricular end-diastolic pressure (RVEDP) were recorded during cardiac catheterization. Ten patients with RAP10 mmHg were classified as Group 1. The remaining 10 patients with RAP=10 mmHg were classified as Group 2. Portal blood velocity profiles were studied using an ultrasonic Doppler within 12 h after cardiac catheterization.CI, AOP, and LVEDP had no difference between two groups. Patients in Group 1 had normal PWP (14.6+/-7.3 mmHg), PAP (25.0+/-8.2 mmHg), RAP (4.7+/-2.4 mmHg), and RVEDP (6.4+/-2.7 mmHg). Patients in Group 2 had increased PWP (29.9+/-9.3 mmHg), PAP (46.3+/-13.2 mmHg), RAP (17.5+/-5.7 mmHg), and RVEDP (18.3+/-5.6 mmHg) (P0.001). Mean values of maximum portal blood velocity (Vmax), mean portal blood velocity (Vmean), cross-sectional area (Area) and portal blood flow volume (PBF) had no difference between 2 groups. All the patients in Group 1 had a continuous antegrade portal flow with a mean percentage of peak-to-peak pulsatility (PP) 27.0+/-8.9 % (range: 17-40 %). All the patients in Group 2 had pulsatile portal flow with a mean PP 86.6+/-45.6 (range: 43-194 %). One patient had a transient stagnant and three patients had a transient hepatofugal portal flow, which occurred mainly during the ventricular systole. Vmax, Vmean and PBF had a positive correlation with CO (P0.001) but not with AOP, LVEDP, PWP, PAP, RAP, and RVEDP. PP showed a good correlation (P0.001) with PWP, PAP, RAP, and RVEDP but not with CI, AOP, and LVEDP. All the patients with PP40 % had a right-sided heart failure with a RAP=10 mmHg.The measurement of PP change is a simple and non-invasive way to identify patients with right heart failure.