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    Review Article Open Access
    Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review
    Deepak Madhu, Sanchit Sharma, Ashish Agarwal, Anoop Saraya
    Journal of Clinical and Translational Hepatology, Published online May 14, 2021. doi:10.14218/JCTH.2021.00001
    Abstract
    The ongoing coronavirus disease-2019 (COVID-19) pandemic has necessitated special considerations in the management of diseases. The way presence of pre-existing diseases or treatment [...] Read more.
    The ongoing coronavirus disease-2019 (COVID-19) pandemic has necessitated special considerations in the management of diseases. The way presence of pre-existing diseases or treatment for it predisposes to, alters course of, and changes the management of COVID-19, is of relevance and is being extensively studied. Autoimmune hepatitis (AIH) is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs, as well as a liver disease with potential for varying degrees of underlying fibrosis. The use of immunosuppressive drugs could alter the risk of acquiring COVID-19, the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19. In this review, we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic. Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence. Full article
    Original Article Open Access
    Development of an Eight-gene Prognostic Model for Overall Survival Prediction in Patients with Hepatocellular Carcinoma
    De-Zhen Guo, Ao Huang, Yu-Peng Wang, Ya Cao, Jia Fan, Xin-Rong Yang, Jian Zhou
    Journal of Clinical and Translational Hepatology, Published online May 14, 2021. doi:10.14218/JCTH.2020.00152
    Abstract
    The overall survival (OS) of hepatocellular carcinoma (HCC) remains dismal. Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical [...] Read more.
    The overall survival (OS) of hepatocellular carcinoma (HCC) remains dismal. Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision. This study aimed to develop a prognostic gene model for HCC. GSE14520 was retrieved as a training set to identify differential expressed genes (DEGs) between tumor and adjacent liver tissues in HCC patients with different OS. A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model. The area under the receiver operating characteristic curve (AUC) and hazard ratio (HR) of the model for OS were calculated. A model-based nomogram was established and verified. In the training set, differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation. After univariate Cox and LASSO regression, eight genes (LPCAT1, DHRS1, SORBS2, ALDH5A1, SULT1C2, SPP1, HEY1 and GOLM1) were selected to build the prognostic model. The AUC for 1-, 3- and 5-year OS were 0.779, 0.736, 0.754 in training set and 0.693, 0.689, 0.693 in the TCGA-LIHC validation set, respectively. The AUC for 1- and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set. Multivariate analysis confirmed the model was an independent prognostic factor (training set: HR=4.422, p<0.001; TCGA-LIHC validation set: HR=2.561, p<0.001; ICGC-LIRI validation set: HR=3.931, p<0.001). Furthermore, a nomogram combining the model and AJCC stage was established and validated, showing increased OS predictive efficacy compared with the prognostic model (p=0.035) or AJCC stage (p<0.001). Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients. Full article
    Original Article Open Access
    Clinical Significance of Liver Function Abnormality in Patients with COVID-19: A Single-center Experience from Western India
    Chetan R. Kalal, Harshad Joshi, Vivek Kumar, Divya Gopal, Darshana Rathod, Ashish Shukla, Tarang Gianchandani, Chetan Bhatt
    Journal of Clinical and Translational Hepatology, Published online May 13, 2021. doi:10.14218/JCTH.2020.00099
    Abstract
    The impact of coronavirus disease-2019 (COVID-19) on liver function remains to be fully elucidated. This study was designed to investigate such and determine the clinical significance [...] Read more.
    The impact of coronavirus disease-2019 (COVID-19) on liver function remains to be fully elucidated. This study was designed to investigate such and determine the clinical significance in determining mortality risk. A retrospective study was conducted in patients with COVID-19 from March 2020 to July 2020. Clinical details were retrieved from electronic medical records to obtain clinical characteristics, medical history, laboratory tests, therapeutic intervention, and outcome data. A total of 184 patients with COVID-19 were included (median age: 45.5 years), comprised of 62.5% men. In total, 22 (12.0%) patients had severe infection and 162 (88.0%) had mild to moderate infection. Overall, 95 (51.6%) showed abnormal liver function test (LFT) and 17 (9.2%) showed normal LFT at admission. The median age, hospital stay, and LFT were significantly higher in severe vs. non-severe infection (p<0.001). Out of 12 deaths, the majority were due to severe infection (n=11). Deaths were also due to acute respiratory distress syndrome (n=5), cardiac reasons (n=3), and sepsis with multiorgan failure (n=3). The median age, hospital stay and number of intensive care unit admissions were higher in patients having abnormal LFT compared to normal LFT. Incidence of elevated aspartate aminotransferase (42.8% and 40.4%), alanine transaminase (43.7% and 41.6%), and hypoalbuminemia (71.4% and72.7%) at admission and discharge were more common in severe infection. The mean survival was significantly lower in severe infection compared to those with non-severe disease (17.2 vs. 52.3 days; p<0.001). Incidence of abnormal liver function was higher in patients with severe COVID-19 and was associated with prolonged hospital stay; mortality was associated with severity of COVID-19. For ruling out the risk of liver injury, it is crucial to vigilantly monitor the liver function parameters in patients with COVID-19 admitted to hospital. Full article

Journals

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    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
    Review Article Open Access
    Current Knowledge on Hepatitis E
    María Teresa Pérez-Gracia, Mario García, Beatriz Suay, María Luisa Mateos-Lindemann
    Journal of Clinical and Translational Hepatology, Published online June 15, 2015. doi:10.14218/JCTH.2015.00009
    Abstract
    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates [...] Read more.
    Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin®. Full article
Special Features

Call for Papers for Special Issue ‘Acute liver failure (ALF)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Acute liver failure (ALF)
Submission deadline: August 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)’

Journal: Journal of Clinical and Translational Hepatology
Special Issue:Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)
Submission deadline: May 31, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Coronavirus Disease (COVID-19) and the Liver’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: Coronavirus Disease (COVID-19) and the Liver
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Prevention & Control of Coronavirus Disease (COVID-19)

Journal: Exploratory Research and Hypothesis in Medicine
Special Issue: Prevention & Control of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Treatment of Coronavirus Disease (COVID-19)’

Journal: Journal of Exploratory Research in Pharmacology
Special Issue: Treatment of Coronavirus Disease (COVID-19)
Submission deadline: June 30, 2021
Publication date: An article will be published online as soon as it is accepted