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    Original Article Open Access
    Approaches to Assessing Burden in Caregivers of Patients with Cirrhosis
    Beshoy Yanny, Nguyen V. Pham, Hussein Saleh, Sammy Saab
    Journal of Clinical and Translational Hepatology, Published online April 7, 2020. doi:10.14218/JCTH.2019.00054
    Abstract
    Background and Aims: Being a caregiver for a patient with chronic liver disease (CLD) can be burdensome mentally, emotionally financially, and physically. The aim of [...] Read more.
    Background and Aims: Being a caregiver for a patient with chronic liver disease (CLD) can be burdensome mentally, emotionally financially, and physically. The aim of this study was to systemically review the available tools and propose tools that can comprehensively evaluate caregiver burden for individuals caring for patients with CLD. Methods: We searched the PubMed database for all studies on the impact of patients with CLD on caregiver burden without timeframe restriction. Eligible studies included cohort studies, review studies, or cross-sectional studies. The number of patients and caregivers was isolated from each paper. Studies in the same categories were isolated and statistically compared. Results: A total of 13 studies meeting our inclusion criteria as stated in the methods sections were included. In total, 2528 caregivers were taking care of 2003 patients with CLD. Women made up the majority of caregivers at 78.2%, 95.7% of whom identified as the patient’s spouse. Caregiver strain index is one of the most comprehensive tools; however, the questions are very general and do not fully elucidate financial strain. Beck depression and anxiety were correlated (p=0.0001), and both depression and anxiety were correlated with perceived caregiver burden (PCB) and Zarit Burden Interview (ZBI) (p=0.002). Depression scale correlated with Interpersonal Support Evaluation – Short Form, and Model for End-Stage Liver Disease score correlated with ZBI and PCB (total and in most domains; p=0.001). Patient’s poorer cognitive performance correlated with higher ZBI and PCB (employed patients had higher cognitive performance and lower ZBI and PCB). Conclusions: Caregiver burden remains poorly understood due to the lack of uniformity in the assessment tools used to evaluate caregiver burden. None of the tools used to evaluate caregiver burden are comprehensive; however, most tools correlate statistically in the ability to identify caregiver burden. A comprehensive tool is lacking for identifying caregiver burden in patients with CLD. Full article
    Review Article Open Access
    Role of Epigenetic Modification of N6-methyladenosine in Phase Separation
    Si-Yu Liu, Yi Feng, Zi-Li Sun, Ming-Li Zou, Jun-Jie Wu, Zheng-Dong Yuan, Feng-Lai Yuan
    Exploratory Research and Hypothesis in Medicine, Published online April 3, 2020. doi:10.14218/ERHM.2019.00028
    Abstract
    In recent years, the development of biophysical analysis methods has crossed with macromolecular condensates in cells. Researchers are interested in membrane-less organelles assembling [...] Read more.
    In recent years, the development of biophysical analysis methods has crossed with macromolecular condensates in cells. Researchers are interested in membrane-less organelles assembling into biomolecule ‘aggregates’ with similar liquid-like properties of phase separation. Cell biologists now think that many of the membrane-less organelles observed in cells are formed by phase separation caused by interactions between proteins and nucleic acids. Phase separation, thus, becomes a major player in the control of a variety of biological functions. Nevertheless, the biophysical regulation of these cells is still poorly understood. Here, we reviewed the current literature that collectively reveals the roles of epigenetic modification of N6-methyladenosine (m6A) in phase separation. Full article
    Review Article Open Access
    Liver Transplantation Beyond Milan Criteria
    Vivek A Lingiah, Mumtaz Niazi, Raquel Olivo, Flavio Paterno, James V Guarrera, Nikolaos T Pyrsopoulos
    Journal of Clinical and Translational Hepatology, Published online March 30, 2020. doi:10.14218/JCTH.2019.00050
    Abstract
    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, being the fifth most common cancer and the third most common cause of cancer-related [...] Read more.
    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, being the fifth most common cancer and the third most common cause of cancer-related mortality. The incidence of HCC has been rising in the USA over the last 20 years. Liver transplantation is an optimal treatment option, as it eliminates HCC as well as the underlying liver disease. The Milan criteria (1 lesion greater than or equal to 2 cm and less than or equal to 5 cm, or up to 3 lesions, each greater than or equal to 1 cm and less than or equal to 3 cm) have been adopted by many transplant societies worldwide as the criteria to determine whether patients with HCC can move forward with liver transplantation. However, many believe that the Milan criteria may be too strict in regard to its size requirements for lesions. This has led to a number of expanded criteria for liver transplantation, concerning both overall size and number of lesions, as well as incorporation of other markers of tumor biology. Tumor markers, such as alpha-fetoprotein, can also be used to follow treatment of HCC and possibly exclude patients from transplant. HCC presenting beyond Milan criteria can also be down-staged with locoregional therapy. Monitoring response to locoregional therapy and longer wait times after locoregional therapy prior to transplant can serve as surrogate markers of tumor biology as well. 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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