Active clinical trials for "Hepatitis"

Hepatitis B virus (HBV) infection is a global health problem, especially in the endemic area like Taiwan, where there are more than 3 million chronic hepatitis B carriers. Patients with chronic HBV infection are at increased risk of developing cirrhosis, which may have disastrous complications, including hepatic decompensation, and hepatocellular carcinoma (HCC). The liver cirrhosis related complications accounts for the 8th leading cause of deaths in Taiwan; whereas, the HCC is the 2nd leading cause of deaths among all cancers. Therefore, it is prudent to develop strategies to prevent or halt the progression of liver cirrhosis. For HBV patients who have already had cirrhosis, the main treatment objective is to reduce their risk of complications. A large-scale multicenter clinical trial showed that viral suppression using lamivudine in patients with advanced fibrosis effectively decreases the risk of HCC and liver-related complications. This study highlights the importance to treat HBV-related cirrhosis patients; however, several issues remain to be addressed. The first issue is that this clinical trial only enrolled patients with positive HBeAg or HBV-DNA level >1.4 x105 IU/mL. However, the current recommended threshold for cirrhotic patients to start anti-viral treatment is 2000 IU/mL. Whether anti-HBV therapy benefits cirrhotic patients in this level is still unclear. Second, lamivudine was used in this clinical trial; however, the high resistant rate of lamivudine during treatment probably lowers its protective effect against HCC. Whether a more potent anti-HBV agent with extremely low resistance profile, entecavir, is more beneficial to HBV-related cirrhotic patients is also unclear. The Bureau of National Health Institute launched the reimbursement program for anti-HBV therapy since 2003 and extended this program to cirrhotic patients with HBV DNA level > 2000 IU/mL for long-term use since Aug, 2010. Taking this advantage, we may explore the above-mentioned clinical questions more easily. To address these issues, we will first retrospectively collect a cohort of HBV-related cirrhosis patients. All the patients will be enrolled from the time before oral anti-HBV therapy is widely used. We will determine their baseline serum HBV-DNA levels using the stored sera and enrolled those with baseline HBV-DNA levels higher than 2000 IU/mL as our historical controls. Second, we will enroll a retrospective cohort of HBV-related cirrhotic patients from 2008 who had HBV-DNA levels higher than 2000 IU/mL and received indefinite therapy of entecavir. By comparing these two cohorts, we will be able to clarify whether indefinite viral suppression by entecavir is beneficial for the cirrhotic patients. With comprehensive analysis, we wish to document that re-setting the risk level of HBV DNA from 140,000 IU/mL to 2,000 IU/mL is more beneficial for HBV-related cirrhotic patients and long-term entecavir does lower the risk of HCC further. These lines of evidence will assist in delivering appropriate and more aggressive treatment for these high-risk patients.

This study aim to find out the risk of exacerbation of chronic hepatitis B after percutaneous radiofrequency ablation (RFA) or hepatectomy for HCC, and it's effect to treatment outcome.

The estimated global prevalence of hepatitis C (HCV) infection is approximately 3% (170 million individuals). In Canada there are an estimated 240,000 people infected with HCV. The current study addresses the hypothesis that neurocognitive and neurochemical abnormalities may occur in individuals with HCV-infection who do not have liver cirrhosis or vasculitic neuropathy, and this may result from a direct effect of HCV on the Central Nervous System (CNS). The purpose of this study is to assess whether infection with the Hepatitis-C virus is associated with changes in thinking skills and brain chemistry, in patients who do not have liver cirrhosis. In addition, we are examining whether such changes in thinking skills and brain chemistry are reversed by antiviral treatment. We are also studying whether factors such as fatigue and depression have an effect on thinking skills in people with Hepatitis-C. In order to take into account the impact of having viral hepatitis, we will be comparing the results of the Hepatitis-C group to the results of a group of patients with Hepatitis-B, and to a group of individuals who do not have Hepatitis.

Chronic viral hepatitis C is a frequent liver disease. It is associated with variable degree of hepatic fibrosis. To date, liver histology is still regarded as the gold standard to detect, diagnose and quantify liver fibrosis. This requires to perform a liver biopsy. Severe complications are associated to this procedure in 0.01 to 0.1% of cases. Because of this, the repetition of the biopsy to evaluate the progression of the disease or the response to treatment poses ethical questions. Also, liver biopsy only explore a minimal portion of the liver and liver fibrosis, which is not homogeneous, may be under- or over-estimated. To avoid risks linked to invasive technique and sampling errors associated to liver biopsy, efforts are being made to develop non-invasive technology to detect and quantitate liver fibrosis. In this study we will perform in patients with chronic hepatitis C, serum tests, fibroscan (elastography of liver parenchyma determined by ultra-sounds), and elastography of liver parenchyma by MRI. This study will allow to determine whether non-invasive tests effectively measure liver fibrosis to compare each non-invase test with results of liver biopsy to determine whether a non-invasive test or a combination of non invasive tests may be used to accurately evaluate liver fibrosis in patients with chronic hepatitis C.

Chronic Hepatitis C virus (HCV) infection is the leading cause of advanced liver disease worldwide. The virus successfully evades host immune detection and has highly restricted requirements for growth in vitro that for many years hampered efforts to find a safe, uncomplicated, and reliable oral antiviral therapy. Ten years after discovery, pegylated interferon-alpha and ribavirin (PR) treatment for 24-48 weeks became the standard of care (1-5). PR therapy offered limited performance and availability across the diverse spectrum of HCV disease and was fraught with excessive and often limiting side effects. The first direct acting agents (DAAs) were protease inhibitors (PIs) that were introduced in 2011 and could only be used only in combination with PR because of concerns for rapid PI viral resistance. Although the first generation PIs added increased efficacy to the PR regimen, they also added new side effects and untoward drug interactions (6-8). Sofosbuvir (SOF) is a potent nucleoside inhibitor (NI) that has recently been approved for treatment of HCV. The drug has low toxicity, high resistance barrier, and minimal drug interactions with other HCV DAAs such as PIs and anti-NS5A agents. SOF is safe and effective across different viral genotypes, disease stages, and special patient groups such as those co-infected with HIV. When used in combination with ribavirin or another DAA, SOF has revolutionized the HCV treatment spectrum and set the stage for nearly universal HCV antiviral therapy. Sustained virologic response (SVR12) for SOF plus ribavirin and pegylated interferon (PR) is 90% for genotype 1 and 85-94% for genotypes 2 and 3 (9-16). SOF plus simeprevir (protease inhibitor) showed a 94% SVR12 for genotype 1 (9-16). More so than any other anti-HCV drug developed to date, SOF offers the widest applicability for all infected patients yet can be given in a personalized regimen to maximize performance

A retrospective and prospective study among people living with HIV (PLWH) that assesses hepatitis C (HCV) treatment uptake during periods before and after direct acting antivirals (DAA) introduction, and its impact on the HCV epidemic among PLWH.

To improve the treatment outcome in patients with tuberculosis and integrate the pharmacogenetics into clinical practice, the information of NAT2 genotyping was used in re-challenge protocol for isoniazid (INH) titration in patients with anti-tuberculosis medication-induced hepatitis.

The purpose of this study is to measure intrahepatic HCV RNA levels at the time of liver transplantation in patients receiving antiviral therapy while on the liver transplant waiting list. This will eventually be correlated with the degree of hepatic fibrosis present within different geographic sites in the cirrhotic liver. Tissue samples will be obtained from the patient's liver explant as well as hilar lymph nodes. Upon the removal of the cirrhotic liver at the time of transplantation, the explant will be biopsied multiple times in different segments of the liver and preserved for viral detection studies as well as analysis of the degree of fibrosis. Peripheral blood mononuclear cells (PBMCs) will be obtained for viral detection at the time of transplantation. Serum HCV RNA levels will also be obtained at 1 month, 3 months and 6 months post liver transplantation. Study Hypotheses: Virological relapse or non-response is higher is patients with cirrhosis due to failure of antiviral medication to concentrate adequately in a fibrotic liver having an altered sinusoidal micro-architecture HCV may persist in different geographic regions of the fibrotic liver in part predicated on blood supply to that area and this may have an effect on overall virological response. These differences in viral persistence and detection may exist in different lobes of the liver or even within a few centimeters within the same portion of the liver parenchyma. PBMC and hilar lymph nodes may be extrahepatic reservoirs of HCV viral persistence in patients receiving antiviral therapy and may account for virological relapse post-therapy There may be varying degrees of fibrosis within the same cirrhotic liver which may impact on hepatic synthetic function and antiviral response to treatment.

Pegylated interferon(IFN) α-2a(Peg-IFN-α) not only inhibit viral replication, but also play an important role in immune regulation, while entecavir(ETV) drugs only inhibit viral replication. In hepatitis B infection, Plasmacytoid Dendritic Cells（pDCs） are the main effector cells in early antiviral innate immune response. This study was aimed at investigating the changes of pDCs frequency and function, and the expression of costimulatory molecules CD86(Cluster of Differentiation antigen 86) during Peg-IFN-αand entecavir(ETV) therapy.Meanwhile, investigators want to verify whether Peg-IFN-α suppressed the virus and the reduction of virus led to the recovery of pDCs function, or Peg-IFN-α enhanced pDCs function which gave rise to the decline of the virus.

Recent TAF has introduced to have more safe profiles than TDF in clinical trials. Especially, TDF has the renal safety issue in high risk group including HIV, decompensated cirrhosis (ascites), uncontrolled DM etc. However, there is no available cohort data for treatment efficacy and safety in TDF-TAF switch therapy in treatment-naïve chronic hepatitis B. The aim of this study is to evaluate safety and efficacy of TAF switch therapy in patients with chronic hepatitis B who have been treated with TDF.