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    Original Article Open Access
    Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C
    Lai Wei, Jia Shang, Yuanji Ma, Xiaoyuan Xu, Yan Huang, Yujuan Guan, Zhongping Duan, Wenhong Zhang, Zhiliang Gao, Mingxiang Zhang, Jun Li, Jidong Jia, Yongfeng Yang, Xiaofeng Wen, Maorong Wang, Zhansheng Jia, Bo Ning, Yongping Chen, Yue Qi, Jie Du, Jianning Jiang, Lixin Tong, Yao Xie, Jinzi J. Wu
    Journal of Clinical and Translational Hepatology, Published online July 22, 2019. doi:10.14218/JCTH.2019.00018
    Abstract
    Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive [...] Read more.
    Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9–99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082 Full article
    Review Article Open Access
    Herbal Medicines for Hepatitis C Virus Infection: The Exploratory Journey from Bench to Bedside Still Has a Long Way to Go
    Xiao-Ya Yang, Yuan-Yuan Zhang, Wen-Rui Xie, Selin Hua He, Li-Hao Wu, Xing-Xiang He, Harry Hua-Xiang Xia
    Journal of Exploratory Research in Pharmacology , Published online June 30, 2019. doi:10.14218/JERP.2019.00003
    Abstract
    Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral [...] Read more.
    Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral therapy is very efficacious in treating HCV infection but it is inaccessible and unavailable in some developing countries. Therefore, searching for more effective and easily accessible regimens remains an urgent need. The aim of this article is to review the anti-HCV effects of herbal medicines from experimental to clinical evidence, and discuss current issues, hurdles and future perspectives for their application from bench to bedside. Numerous in vitro studies have indicated that many herbs work effectively in exerting anti-HCV activities. Yet, only a few animal experiments have been conducted that demonstrate the anti-HCV effects of these medicines; in addition, these results do not show an ability to eliminate the virus completely from the infected animals. Thus far, clinical trials have produced inconclusive anti-HCV results in terms of efficacy and safety, presumably due to the lack of the quality of methodologies used in the trials. In conclusion, despite apparent anti-HCV activities in vitro, clinical efficacy and safety of herbal medicines for the treatment of HCV infection have not been revealed convincingly. More animal studies using ideal models and more well-designed clinical trials with a larger sample sizes and longer treatment periods, taking the body habitus into consideration, are required to further assess the efficacy and safety of herbal medicines for HCV infection. Full article
    Review Article Open Access
    Update on Management of Portal Vein Thrombosis and the Role of Novel Anticoagulants
    Matthew Wu, Michael Schuster, Micheal Tadros
    Journal of Clinical and Translational Hepatology, Published online June 28, 2019. doi:10.14218/JCTH.2018.00057
    Abstract
    The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable [...] Read more.
    The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable states. The natural history and clinical outcome of PVT are highly variable, dependent upon size, extent and degree of the thrombotic occlusion, as well as the physiological impact of patient comorbidities. While existing clinical guidelines consistently recommend low molecular weight heparin or vitamin K antagonist anticoagulation in cirrhotic patients with symptomatic acute PVT, management of asymptomatic and chronic PVT may need to be determined on a case-by-case basis, factoring in the state of underlying liver disease. In general, patients with PVT and underlying malignancy should be anticoagulated to alleviate symptoms and prevent recurrences that could disrupt the cancer management. However, existing clinical data does not support routine anticoagulation of cirrhotic patients with asymptomatic PVT in the absence of underlying cancer. While low molecular weight heparin and vitamin K antagonist remain the most commonly used agents in PVT, an emerging body of clinical evidence now suggests that direct-acting oral anticoagulants may be used safely and effectively in PVT. As such, direct-acting oral anticoagulants may offer a more convenient anticoagulation alternative for PVT management in future practice. Full article

Journals

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    Review Article Open Access
    Current and Future Treatment of Hepatocellular Carcinoma: An Updated Comprehensive Review
    Saleh Daher, Muhammad Massarwa, Ariel A. Benson, Tawfik Khoury
    Journal of Clinical and Translational Hepatology, Published online December 17, 2017. doi:10.14218/JCTH.2017.00031
    Abstract
    Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality. The principal treatment is surgical resection or liver transplantation, depending on whether [...] Read more.
    Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality. The principal treatment is surgical resection or liver transplantation, depending on whether the patient is a suitable transplant candidate. However, in most patients with HCC the diagnosis is often late, thereby excluding the patients from definitive surgical resection. Medical treatment includes sorafenib, which is the most commonly used systemic therapy; although, it has been shown to only minimally impact patient survival by several months. Chemotherapy and radiotherapy are generally ineffective. Due to the poor prognosis of patients with HCC, newer treatments are needed with several being in development, either in pre-clinical or clinical studies. In this review article, we provide an update on the current and future medical and surgical management of HCC. Full article
    Review Article Open Access
    Current Management of Alcoholic Hepatitis and Future Therapies
    Behnam Saberi, Alia S. Dadabhai, Yoon-Young Jang, Ahmet Gurakar, Esteban Mezey
    Journal of Clinical and Translational Hepatology, Published online June 28, 2016. doi:10.14218/JCTH.2016.00006
    Abstract
    Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. [...] Read more.
    Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply. Full article
    Review Article Open Access
    Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update
    Eric Yoon, Arooj Babar, Moaz Choudhary, Matthew Kutner, Nikolaos Pyrsopoulos
    Journal of Clinical and Translational Hepatology, Published online June 15, 2016. doi:10.14218/JCTH.2015.00052
    Abstract
    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone [...] Read more.
    Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways. Full article
Special Features

Author Interview: Ashwani Singal 

Author of "Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases"

J Clin Transl Hepatol. 2015 Mar; 3(1): 9–16. Published online 2015 Mar 15. doi: 10.14218/JCTH.2015.00001.

Author Interview: Lucija Virovic Jukic

Author of "Hepatitis C Virus, Insulin Resistance, and Steatosis"

J Clin Transl Hepatol. 2016 Mar; 4(1): 66–75. Published online 2015 Mar 15. doi: 10.14218/JCTH.2015.00051.

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