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Results in Journal Journal of Clinical and Translational Hepatology: 394

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Yang Yang, Yu Yan, Zhen Chen, Jie Hu, Kai Wang, Ni Tang, Xiaosong Li, Zhi Zhou
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00105

Yue Wu, Ying Yang, Fang Li, Jie Zou, Yu-Hao Wang, Meng-Xia Xu, Yong-Lun Wang, Rui-Xi Li, Yu-Ting Sun, Shun Lu, et al.
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2021.00050

Wei-Feng Hong, Yu-Jun Gu, Na Wang, Jie Xia, Heng-Yu Zhou, Ke Zhan, Ming-Xiang Cheng, Ying Cai
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00132

Winston Hernández-Ceballos, Jacqueline Cordova-Gallardo, Nahum Mendez-Sanchez
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00131

Mengdi Jin, Qiong Yu, Yahui Liu, Weiling Xu, Xueqi Fu, Bai Ji
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00125

Yanyun Shu, Yuhu Song, Tao Bai, Xiaoli Pan, Haitao Shang, Ling Yang, Jin Ye, Fan Du
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00127

Wen-Yue Liu, Mohammed Eslam, Kenneth I. Zheng, Hong-Lei Ma, Rafael S. Rios, Min-Zhi Lv, Gang Li, Liang-Jie Tang, Pei-Wu Zhu, Xiao-Dong Wang, et al.
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00151

Coronavirus disease 2019 (COVID-19) has infected over 93 million people worldwide as of January 14, 2021. Various studies have gathered data on liver transplant patients infected with COVID-19. Here, we discuss the presentation of COVID-19 in immunosuppressed patients with prior liver transplants. We also evaluate patient outcomes after infection.
Junyu Huo, Liqun Wu, YunJin Zang
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00114

Growing evidence suggests that metabolic-related genes have a significant impact on the occurrence and development of hepatocellular carcinoma (HCC). However, the prognostic value of metabolic-related genes for HCC has not been fully revealed.
Madhumita Premkumar, Rohit Mehtani, Smita Divyaveer, Kamal Kajal, Anand V. Kulkarni, Syed Ahmed, Harmanpreet Kaur, Harpreet Kaur, Radhakrishna Dhiman, Ajay Duseja, et al.
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00121

Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.
David J. Hermel, Emma Z. Du, Ray Lin, Catherine T. Frenette, Darren S. Sigal
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00094

Qiu-Yu Li, Zhuo-Yu An, Chao Li, Ming Zu, Lei Chen, Jia-Nan Zhang, Yang-Yu Zhao, Ning Shen, Qing-Gang Ge
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00085

Currently, infection with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during pregnancy is a problem worthy of attention, especially in patients with underlying diseases. In this case report, we present a case of chronic active hepatitis B with COVID-19 in pregnancy. A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment, was admitted to the hospital with chronic active hepatitis B, and tested positive for SARS-CoV-2 infection. In this case, we applied liver protective and antiviral agents, and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.
Xiaoqing Liu,
Journal of Clinical and Translational Hepatology; doi:10.14218/jcth.2020.00078

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease, including decompensated cirrhosis and hepatocellular carcinoma. Over 95% of patients with HCV infection have achieved sustained virologic response at 12 weeks under the treatment of several pan-genotypic regimens approved for patients with HCV infection. The glecaprevir/pibrentasvir (G/P) regimen has some features that distinguish it from others and is the only 8-week regimen approved for treatment-naive patients and patients experienced in regimens containing (peg)interferon, ribavirin, and/or sofosbuvir, without an HCV NS3/4A protease inhibitor or NS5A inhibitor (except those with genotype 3). This review aims to summarize the efficacy and safety of G/P in HCV-infected patients from clinic trials and real-world studies, including those who have historically been considered difficult to cure.
Vinka Rupcic Rubin, , Martina Smolic, Jurica Rubin, Ashraf Tabll, Robert Smolic
Journal of Clinical and Translational Hepatology, pp 1-11; doi:10.14218/jcth.2020.00040

Liver fibrosis represents a response to chronic liver injury. Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases, both with increasing incidence. Therefore, there is a great impetus for development of agents targeting these conditions. Accumulating data on possible treatment options for liver fibrosis are emerging in the literature. However, despite extensive research and much effort in the field, approved agents for liver fibrosis are still lacking. In this critical review, we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials, with an emphasis on efficacy and safety of these agents.
, Zeba Haque
Journal of Clinical and Translational Hepatology, pp 1-7; doi:10.14218/jcth.2019.00046

Multiple non-invasive methods including radiological, anthropometric and biochemical markers have been reported with variable performance. The present study assessed glycosylated hemoglobin (HbA1C) as a biomarker to predict non-alcoholic fatty liver disease (NAFLD) and its severity, compared with body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC) This case control study included 450 individuals, including 150 cases and 300 age- and gender-matched controls recruited from the Dow Radiology Institute on the basis of radiological findings of fatty infiltration on abdominal ultrasound through convenient sampling. BMI, WHR and WC were measured according to standard protocols. HbA1C was determined by turbidimetric inhibition immunoassay Among the cases and controls, 66% and 32% had HbA1C levels higher than 5.7% respectively. HbA1C and BMI were significantly associated with NAFLD [crude odds ratio (cOR)=4.12, 2.88, 2.25 (overweight) and 4.32 (obese)]. WC was found to be significantly associated with NAFLD for both genders (cOR in males=5.50 and females=5.79, p<0.01). After adjustment for other parameters, HbA1C and WC were found to be significantly associated with NAFLD (aOR=3.40, p<0.001) along with WC in males (aOR=2.91, p<0.05) and in females (aOR=4.28, p<0.05). A significant rise in severity of hepatic steatosis was noted with increases in HbA1C, BMI and WC. HbA1C possessed a positive predictive value of 76% for the study population [0.76, confidence interval (CI): 0.715-0.809], 70.6% for males (0.706, CI: 0.629-0.783) and 80% for females (0.80, CI: 0.741-0.858). Higher than normal HbA1C and WC measurements possess a more than 70% potential to predict NAFLD. It is the single risk factor that is strongly associated with NAFLD after adjustment for indices of body measurements. HbA1C may be presented as a potential biomarker for NAFLD in examination with other anthropometric measures in the adult population.
, George Y. Wu
Journal of Clinical and Translational Hepatology, pp 1-10; doi:10.14218/jcth.2020.00088

Human cytomegalovirus (HCMV) infection is common and affects between 40–100% of the worldwide population. However, the majority of cases are asymptomatic and when severe disease occurs, it is usually restricted to immunocompromised patients. Liver involvement by HCMV differs significantly, accordingly to the immune status of the host. In immunocompromised patients, particularly liver transplant patients, it often causes clinically significant hepatitis. On the other hand, in immunocompetent patients, HCMV hepatitis requiring hospitalization is extremely rare. This review aims to appraise studies regarding the pathophysiology of HCMV hepatitis, including mechanisms of latency and reactivation and its contribution to disease development, clinical presentation, diagnostic modalities and treatment, with a focus on comparing different aspects between immunocompromised and immunocompetent hosts.
Qiaoling Wang, Binxia Chang, Xiaoyan Li,
Journal of Clinical and Translational Hepatology, pp 1-9; doi:10.14218/jcth.2020.00104

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver disease. ALDH2 gene mutations exist in about 8% of the world’s population, with the incidence reaching 45% in East Asia. The mutations will result in impairment of enzyme activity and accumulation of acetaldehyde, facilitating the progression of other liver diseases, including non-alcoholic fatty liver diseases, viral hepatitis and hepatocellular carcinoma, through adduct formation and inflammatory responses. In this review, we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases, with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.
Jie Wang, Yi Lou, Jianmin Lu, Yuxiao Luo, Anqian Lu, Anna Chen, Jiantao Fu, Jing Liu, Xiang Zhou, Jin Yang
Journal of Clinical and Translational Hepatology, pp 1-10; doi:10.14218/jcth.2020.00084

Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma (HCC), but the rapid growth inherent to such tumor development remains to be explored. We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis. Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth. Hub genes in the modules were determined, examined in vitro, and further assembled into the growth signature. We revealed modules related to the different growth states in HCC, especially the fastest growth module, which is preserved among different HCC cohorts. Moreover, signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth. Twenty hub genes in the module were identified and assembled into the growth signature, and two genes (NCAPH, and RAD54L) were tested for their growth potential in vitro. Genetic alteration of the growth signature affected the global gene expression. The activity of the signature was associated with tumor metabolism and immunity in HCC. Finally, the prognosis effect of the growth signature was reproduced in nine cancers. These results collectively demonstrate the molecule organization of rapid tumor growth in HCC, which is a highly synergistic process, with implications for the future management of patients.
Kevin M. Towle, Stacey M. Benson, Natalie S. Egnot,
Journal of Clinical and Translational Hepatology, pp 1-7; doi:10.14218/jcth.2020.00073

The goal of this analysis was to evaluate the association between county-level ambient vinyl chloride (VC) and county-level liver cancer incidence and mortality rates in Texas. Modeled county-level ambient VC data were obtained from the National Air Toxics Assessment. Age-adjusted county-level liver cancer incidence rates were abstracted from the Texas Cancer Registry and age-standardized county-level liver cancer mortality rates were obtained from the peer-reviewed literature. Multivariable imputation was utilized to impute incidence rates in counties with suppressed liver cancer incidence rates. Negative binomial and Poisson regression models were utilized to evaluate the association between county-level ambient VC and county-level liver cancer incidence and mortality rates, respectively, adjusted for county-level heavy drinking prevalence, hepatitis mortality rates, median income, and race (percent Hispanic). County-level ambient VC was not associated with county-level liver cancer incidence or mortality rates. Specifically, when compared to the lowest tertile of ambient VC, the middle (relative risk [RR]: 1.06, 95% confidence interval [CI]: 0.95–1.19) and highest (RR: 1.03, 95% CI: 0.90–1.17) tertiles of ambient VC were not associated with liver cancer incidence. Similarly, county-level ambient VC in the middle (RR: 0.95, 95% CI: 0.85–1.05) and highest (RR: 0.93, 95% CI: 0.82–1.05) tertiles were not associated with liver cancer mortality. This analysis suggests that county-level ambient VC is not associated with liver cancer incidence or mortality in Texas. Our study provides novel results regarding liver cancer risk from low-level non-occupational exposure to ambient VC.
Harry Hua-Xiang Xia, George Y. Wu,
Journal of Clinical and Translational Hepatology, Volume 8, pp 357-358; doi:10.14218/jcth.2020.00138

Editorial Office of Journal of Clinical and Translational Hepatology
Journal of Clinical and Translational Hepatology, Volume 8, pp 479-481; doi:10.14218/jcth.2020.000ra

Vivek A. Lingiah, Nikolaos T. Pyrsopoulos
Journal of Clinical and Translational Hepatology, pp 1-8; doi:10.14218/jcth.2020.00076

Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population. The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections, bacteria isolated, therapeutic regimens used, and mortality. This was a retrospective chart review study, including 192 patients. All patients had a diagnosis of cirrhosis and were admitted to University Hospital. Information collected included demographics, etiology of cirrhosis, identification of bacteria from cultures, multidrug-resistant (MDR) status, antibiotics administered, intensive care unit (ICU) admission, and patient mortality. Infections were present in 105 (54.6%) patients, and 60 (31.2%) patients had multiple infections during a hospitalization(s) for infections. A total of 201 infections were identified. Urinary tract infections (UTIs) were the most common infection (37.8%), followed by bacteremia (20.4%), pneumonia (12.9%), spontaneous bacterial peritonitis (SBP) (11.9%), abscess/cellulitis (6.0%), infectious diarrhea (6.0%), and other (5.0%). Escherichia coli was the most common bacteria isolated (13.4%), both among sensitive and MDR infections. MDR bacteria were the cause for 41.3% of all infections isolated. Fungi accounted for 9.5% of infections. 21.9% of patients had decompensation from their infection(s) that required ICU care, and 14.6% of patients died during hospitalization or soon after discharge. The incidence of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts (54.6%), even higher than prior studies suggest. As many of these infections are caused by MDR bacteria and fungal organisms, stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population. However, once organism sensitivities are discovered, narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.
Qianhui Chen, Xinyu Lu,
Journal of Clinical and Translational Hepatology, pp 1-9; doi:10.14218/jcth.2020.00063

The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating multiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.
, Qi Yu, Zaid Tafesh, Nikolaos Pyrsopoulos
Journal of Clinical and Translational Hepatology, pp 1-10; doi:10.14218/jcth.2020.00082

Globally, the rise in prevalence of obesity and metabolic syndrome as a whole has been linked to increased access to processed foods, such as refined sugars and saturated fats. Consequently, nonalcoholic fatty liver disease (NAFLD) is on the rise in both developed and developing nations. However, much is still unknown on the NAFLD phenotype with regards to the effect of ethnic diversity. Despite similarities in dietary habits, it appears that certain ethnicities are more protected against NAFLD than others. However, manifestations of the same genetic polymorphisms in different groups of people increase those individuals’ predisposition to NAFLD. Diets from different regions have been associated with a lower prevalence of NAFLD and have even been linked to regression of hepatic steatosis. Socioeconomic variations amongst different regions of the world also contribute to NAFLD prevalence and associated complications. Thus, a thorough understanding of ethnic variability in NAFLD is essential to tailoring treatment recommendations to patients of different backgrounds.
Shousheng Liu, Jianhan Xiao, Zhenzhen Zhao, Mengke Wang, Yifen Wang,
Journal of Clinical and Translational Hepatology, pp 1-12; doi:10.14218/jcth.2020.00081

Accumulated studies have reported the key role of circulating fetuin-A in the development and progression of nonalcoholic fatty liver disease (NAFLD) but the results have not been consistent. In this study, we performed a systematic review and meta-analysis to explore the relationship between circulating fetuin-A level and the development and classification of NAFLD. The PubMed, EMBASE, and Cochrane Library databases were searched to obtain the potentially relevant studies up to May 2020. Standardized mean differences (SMD) and 95% confidence intervals of circulating fetuin-A levels were extracted and summarized. Sensitivity, subgroup analysis and meta-regression analysis were performed to investigate the potential heterogeneity. Association of circulating fetuin-A level with classification of NAFLD was also reviewed. A total of 17 studies were included, composed of 1,755 NAFLD patients and 2,010 healthy controls. Meta-analysis results showed that NAFLD patients had higher circulating fetuin-A level (SMD=0.43, 95% confidence interval [CI]: 0.22–0.63, p<0.001) than controls. Subgroup analysis indicated that circulating fetuin-A level was markedly increased in adult NAFLD patients (SMD=0.48, 95% CI: 0.24–0.72, p<0.001) and not in pediatric/adolescent patients compared to controls. Circulating fetuin-A level was markedly increased in ultrasound-proven NAFLD pediatric/adolescent patients (SMD=0.42, 95% CI: 0.12–0.72, p=0.007), other than in the liver biopsy-proven NAFLD pediatric/adolescent patients. Body mass index might be the influencing factor to the heterogeneity in adult patients. Circulating fetuin-A level was not associated with the classification of NAFL vs. nonalcoholic steatohepatitis (NASH). Whether the circulating fetuin-A level was associated with the development of fibrosis remains controversial. Circulating fetuin-A level was significantly higher in NAFLD patients and was not associated with the classification of NAFL vs. NASH. Whether the circulating fetuin-A level was associated with the development of fibrosis remains controversial.
Mithun Sharma, , , , D Nageshwar Reddy, Nagaraja Padaki Rao
Journal of Clinical and Translational Hepatology, pp 1-11; doi:10.14218/jcth.2020.00055

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH; moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.
Harjot K. Bedi, , , Gordon Ritchie, , Vladimir Marquez,
Journal of Clinical and Translational Hepatology, pp 1-3; doi:10.14218/jcth.2020.00090

Occult hepatitis B infection is characterized by loss of hepatitis B surface antigen (HBsAg) and persistence of low levels of hepatitis B virus (HBV) replication that may or may not be detectable in plasma/serum. We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C (HCV) infection. Pre-transplant, he was HBsAg-negative and hepatitis B core antibody-positive, with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant. Post-transplant, his HBsAg remained undetectable, with an undetectable HBV viral load, until eradication of his HCV infection with direct acting antiviral agents. After eradication of HCV, there was reactivation of HBV, with a high viral load and emergence of serum HBsAg. A deep sequencing genetic analysis of his HBV both pre- and post-transplant revealed the presence of a mutation in the “a” determinant of the HBV surface antigen. The role of HBV genotype ‘a’ determinant mutation in HBV reactivation post-transplant is unknown and needs further examination. Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.
, George Y. Wu
Journal of Clinical and Translational Hepatology, pp 1-9; doi:10.14218/jcth.2020.00089

Aminotransferases are commonly found to be elevated in patients with celiac disease in association with two different types of liver dysfunction: cryptogenic liver disorders and autoimmune disorders. The purpose of this review is to discuss the mechanisms by which aminotransferases become elevated in celiac disease, clinical manifestations, and response to gluten-free diet. Many studies have shown that celiac patients with cryptogenic liver disease have normalization in aminotransferases, intestinal histologic improvement and serologic resolution after 6–12 months of strict gluten-free diet. In patients with an underlying autoimmune liver disease, simultaneous treatment for both conditions resulted in normalized elevated aminotransferases. The literature suggests that intestinal permeability may be at least one of the mechanisms by which liver damage occurs. Patients with celiac disease should have liver enzymes routinely checked and treated with a strict gluten-free diet if found to be abnormal. Lack of improvement in patients who have strictly adhered to gluten-free diet should prompt further workup for other causes of liver disease.
Sanja Stojsavljevic-Shapeski, Marko Duvnjak, Lucija Virovic-Jukic, Davor Hrabar, Lea Smircic Duvnjak
Journal of Clinical and Translational Hepatology, pp 1-9; doi:10.14218/jcth.2020.00057

Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and other end-stage liver disease complications. When addressing treatment of NASH, we have limited approved options, and the mainstay of therapy is lifestyle intervention. Extensive research and revelation in the field of pathogenesis of NASH has offered new possibilities of treatment and emerging new drugs that are being tested currently in numerous preclinical and clinical trials. These drugs target almost all steps in the pathogenesis of NASH to improve insulin sensitivity, glucose and lipid metabolism, to inhibit de novo lipogenesis and delivery of lipids to the liver, and to influence apoptosis, inflammation and fibrogenesis. Although NASH is a multifactorial disease, in the future we could identify the predominating pathological mechanism and, by choosing the most appropriate specific medication, tailor the treatment for every patient individually.
Manus Rugivarodom,
Journal of Clinical and Translational Hepatology, Volume 9, pp 1-13; doi:10.14218/jcth.2020.00067

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.
, Shubhra Upadhyay, Rahul Shekhar, Euriko Torrazza-Perez
Journal of Clinical and Translational Hepatology, Volume 9, pp 1-4; doi:10.14218/jcth.2020.00053

The novel coronavirus 2019 (COVID-19) was reported by the World Health Organization in December 2019, and since then it has progressed into a worldwide pandemic, causing significant morbidity and mortality. Gastrointestinal symptoms of COVID-19 and elevated liver chemistries are seen in up to 50% of infected patients. Recent reports have suggested a high mortality rate for COVID-19 in patients with pre-existing liver disease, having an associated mortality of 39.8%. Alcoholic liver disease is a significant cause of morbidity and mortality in New Mexico (USA), and we report here the clinical course and characteristics of three cases of patients with alcoholic cirrhosis who were admitted to our hospital with COVID-19.
Jinfeng Liu, Tianyan Chen, Yaolong Chen, , Guiqiang Wang, ,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-10; doi:10.14218/jcth.2020.00070

To develop the evidence-based guidelines for managing mother-to-child transmission of hepatitis B virus in China, a multidisciplinary guideline development group was established. Clinical questions were identified from two rounds of surveys on the concerns of first-line clinicians. We conducted a comprehensive search and review of the literature. A grading of recommendations’ assessment, development, and evaluation system was adopted to rate the quality of evidence and the strength of recommendations. Recommendations were formulated based on the evidence, overall balance of benefits and harms (at individual and population levels), patient/health worker values and preferences, resources available, cost-effectiveness, and feasibility. Eventually, recommendations related to 13 main clinical concerns were developed, covering diagnostic criteria, treatment indications, antiviral therapy choice, timing to initiate and discontinue treatment, immunoprophylaxis strategy at birth, and how to deal with special situations, such as unintended pregnancy, assisted reproduction, and breastfeeding. The guidelines are intended to serve as guidance for clinicians and patients, to optimize the management of majority of pregnant women who are positive for hepatitis B surface antigen. Guideline registration: International Practice Guide Registration Platform (IPGRP-2018CN040).
, Nathalie A Pena Polanco, Aymara Fernandez De La Vara, Cynthia Levy
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-6; doi:10.14218/jcth.2020.00006

Background and Aims: Hispanic patients with primary biliary cholangitis (PBC) have reduced rates of biochemical response to ursodeoxycholic acid (UDCA) and increased risk of disease progression compared to non-Hispanic patients. In this study, we sought to identify differences in demographics, comorbidities, environmental risk factors and socioeconomic status between Hispanic and non-Hispanic patients with PBC.
, Upenkumar Patel, Shiva Arjun, Kristen Farraj, Kevin Yeroushalmi, Sandra Gomez Paz, Jaehyuck Im, Andres Castillo, Rajmohan Rammohan, Paul Mustacchia
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-3; doi:10.14218/jcth.2020.00075

Sean P. Tighe, Daud Akhtar, , Aijaz Ahmed
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-5; doi:10.14218/jcth.2020.00012

Chronic liver disease (CLD) is an under-recognized epidemic that continues to increase in prevalence and is a major health concern. Silymarin, the active compound of Silybum marianum (Milk thistle), has historically been used in CLD. A significant barrier to silymarin use is its poor bioavailability. Attempts at improving the bioavailability of silymarin have led to a better understanding of formulation methods, pharmacokinetics, dosing, and associated drug interactions. Clinically, silymarin exerts its hepatoprotective effects through antioxidative, antifibrotic, anti-inflammatory, antitoxin, and anticancerous mechanisms of actions. Despite the use of silymarin being extensively studied in alcoholic liver disease, metabolic-associated fatty liver disease, viral hepatitis, and drug-induced liver injury, the overall efficacy of silymarin remains unclear and more research is warranted to better elucidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects. Here, we review the current biochemical and clinical evidence regarding silymarin in CLD.
Sarah Altajar,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-10; doi:10.14218/jcth.2020.00065

The association between the pathogenesis and natural course of nonalcoholic fatty liver disease (NAFLD) and skeletal muscle dysfunction is increasingly recognized. These obesity-associated disorders originate primarily from sustained caloric excess, gradually disrupting cellular and molecular mechanisms of the adipose–muscle–liver axis resulting in end-stage tissue injury exemplified by cirrhosis and sarcopenia. These major clinical phenotypes develop through complex organ–tissue interactions from the earliest stages of NAFLD. While the role of adipose tissue expansion and remodeling is well established in the development of NAFLD, less is known about the specific interplay between skeletal muscle and the liver in this process. Here, the relationship between skeletal muscle and liver in various stages of NAFLD progression is reviewed. Current knowledge of the pathophysiology is summarized with the goal of better understanding the natural history, risk stratification, and management of NAFLD.
, Anand Kulkarni, Mitnala Sasikala, Pramod Kumar, Shasidhar Jaggaiahgari, Kumar Pondugala, Ganesh Jaishetwar, Santosh Darisetty, Nitin Jagtap, Rajesh Gupta, et al.
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-6; doi:10.14218/jcth.2020.00052

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking.
Xin Yan, Wenwen Jin, Jie Zhang, Mengke Wang, ,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-6; doi:10.14218/jcth.2020.00071

Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population.
Yujia Li, Shilin Li, Xiaoqiong Duan, Chunhui Yang, Min Xu,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-8; doi:10.14218/jcth.2020.00046

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.
Ahyoung Kim, Bolin Niu, Tinsay Woreta,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-7; doi:10.14218/jcth.2020.00058

Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalopathy and impaired synthetic function (international normalized ratio of ≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulopathy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagulable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.
Ashok Choudhury, Golamari Srinivasa Reddy, Shantan Venishetty, Viniyendra Pamecha, Saggere Muralikrishna Shasthry, Arvind Tomar, Lalita Gauri Mitra, Venkata Siva Tez Prasad, Rajendra Prasad Mathur, Debajyoti Bhattacharya, et al.
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-7; doi:10.14218/jcth.2020.00061

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.
Catherine Choi, Youssef Botros, Jamil Shah, Pei Xue, Anja Jones, Mark Galan, Raquel Olivo, Mumtaz Niazi, Flavio Paterno, James Guarrera, et al.
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-4; doi:10.14218/jcth.2020.00062

Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later developed alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilaprevir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.
, Alex Y Chang, Atif Zaman, Paul Martin, Conrado M Fernandez-Rodriguez, Mete Korkmaz, Simona Rossi, James M Ford, Tamara Noonan, Elizabeth Cooney, et al.
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-8; doi:10.14218/jcth.2020.00039

Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes.
Qiuli Xie, Yingen Feng, Jing Li, Xiaoqiao Chen,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-2; doi:10.14218/jcth.2020.00038

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addition to the clinical characteristics and genetic history, electromyography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possibility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.
Khalid Alsawat, Almoutaz Hashim, Mohamed Alboraie,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-2; doi:10.14218/jcth.2020.00049

Hong Wei, Bin Song
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-9; doi:10.14218/jcth.2020.00033

Chronic hepatitis B or C viral infection is a common cause of liver cirrhosis and hepatocellular carcinoma. Fibrosis regression can be achieved after long-term antiviral therapy (AVT). Monitoring of dynamic changes in liver fibrosis after treatment is essential for establishing prognosis and formulation of a follow-up surveillance program. Routine surveillance of fibrosis after AVT by liver biopsy, the gold standard for fibrosis assessment, is hindered by its invasive nature, sampling error and observer variability. Elastography is a noninvasive quantitative alternative that has been widely used and validated for the staging of liver fibrosis prior to treatment. Recently, increasing research interest has been focused on the role of elastography in longitudinal assessment of liver fibrosis after AVT. In this review, the basic principles, acquisition techniques, diagnostic performances, and strengths and limitations of ultrasound elastography and magnetic resonance elastography are presented. Emerging evidence regarding the use of elastography techniques for the monitoring of liver fibrosis after AVT is summarized. Current challenges and future directions are also discussed, designed to optimize the application of these techniques in clinical practice.
Huiying Rao, Xingxiang Yang, Youwen Tan, Qin Ning, Daokun Yang, Jiefei Wang, Yongfeng Yang, Sujun Zheng, Dongliang Yang, Jinlin Hou, et al.
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-7; doi:10.14218/jcth.2020.00031

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety.
Hong-Qin Xu, Chun-Guang Wang, Peng Xiao, Yan-Hang Gao
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-10; doi:10.14218/jcth.2020.00047

Background and Aims: Glecaprevir/pibrentasvir is a pangenotypic regimen recently approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the present review was to summarize the findings from clinical trials to understand how patient-related factors influence glecaprevir/pibrentasvir efficacy (sustained virologic response rates at 12 weeks’ after treatment [referred to as SVR12]) and safety.
, George Y. Wu
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-11; doi:10.14218/jcth.2020.00036

Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are slow progressive diseases which have been increasing in prevalence. The pathogeneses of PBC and PSC are incompletely understood but the underlying mechanisms appear to be fundamentally autoimmune in origin. Although PBC and PSC appear to be separate entities, overlap has been described. Diagnosis depends on a combination of serological markers, imaging, and pathological criteria. The mainstay of treatment has been ursodeoxycholic acid and in some cases of extrahepatic biliary obstruction and overlap disorder, endoscopic retrograde cholangiopancreatography has been useful.
Yue-Cheng Guo,
Journal of Clinical and Translational Hepatology, Volume 8, pp 1-9; doi:10.14218/jcth.2020.00023

Liver fibrosis is not an independent disease. It refers to the abnormal proliferation of connective tissues in the liver caused by various pathogenic factors. Thus far, liver fibrosis has been considered to be associated with a set of factors, such as viral infection, alcohol abuse, non-alcoholic fatty liver disease, and autoimmune hepatitis, as well as genetic diseases. To date, clinical therapeutics for liver fibrosis still face challenges, as elimination of potential causes and conventional antifibrotic drugs cannot alleviate fibrosis in most patients. Recently, potential therapeutic targets of liver fibrosis, such as metabolism, inflammation, cell death and the extracellular matrix, have been explored through basic and clinical research. Therefore, it is extremely urgent to review the antihepatic fibrosis therapeutics for treatment of liver fibrosis in current clinical trials.
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