A large proportion of patients with chronic hepatitis C have associated thrombocytopenia (TCP). Due to bleeding risks, TCP, when severe, can limit diagnostic and therapeutic procedures, treatments, and increases risk of complications, especially excessive bleeding. It is important to understand the mechanisms that cause TCP in order to manage it. In general, TCP can be due to increased destruction or decreased production. Proposed mechanisms of increased destruction include autoantibodies to platelets and hypersplenism with sequestration. Proposed mechanisms of decreased production include virus-induced bone marrow suppression and decreased TPO production. Autoantibodies directed against platelet surface antigens have demonstrated an inverse correlation with platelet counts. Hypersplenism with sequestration involves the interaction of portal hypertension, splenomegaly, and platelet destruction. Decreased production mechanisms involve appropriate and inappropriate levels of TPO secretion. There is limited evidence to support viral-induced bone marrow suppression. In contrast, there is strong evidence to support low levels of TPO in liver failure as a major cause of TCP. TPO-agonists, specifically eltrombopag, have been shown in hepatitis C patients to increase platelet counts without reducing portal hypertension or splenomegaly. We conclude that TCP in hepatitis C virus-induced liver disease is often multifactorial, but an understanding of the mechanisms can lead to judicious use of new drugs for treatment.

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.

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.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (2019 coronavirus disease, COVID-19) since December 2019, from Wuhan, China, has been posing a significant threat to global human health. The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported. Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients, and it is often manifested as transient elevation of serum aminotransferases; however, the patients seldom have liver failure and obvious intrahepatic cholestasis, unless pre-existing advanced liver disease was present. The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress, systemic inflammation response, drug toxicity, and progression of pre-existing liver diseases. However, there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present. The clinical, pathological and laboratory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear. In this review, we highlight these important issues based on the recent developments in the field, for optimizing the management and treatment of liver injury in Chinese patients with COVID-19.

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.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.

Annually, 10% of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis (LVP) is a frequently used therapeutic procedure. LVP, although a safe method, is associated with circulatory dysfunction in a significant percentage of patients, which is termed paracentesis-induced circulatory dysfunction (PICD). PICD results in faster reaccumulation of ascites, hyponatremia, renal impairment, and shorter survival. PICD is diagnosed through laboratory results, with increases of >50% of baseline plasma renin activity to a value ≥4 ng/mL/h on the fifth to sixth day after paracentesis. In this review, we discuss the pathophysiology and prevention of PICD.

Chronic hepatitis C infection in the USA is a highly morbid condition and current guidelines recommend one-time screening among the birth cohort (1945-1965). Understanding strategies to optimize screening can help inform future hepatitis C virus (HCV) screening guidelines. A focused literature search was performed using PubMed and manual abstract review from major hepatology conferences over the past 2 years. The search strategy involved using Medical Subject Headings terms for hepatitis C, screening, birth cohort, baby boomers, and 1945-1965. The review was limited to data from the USA. A total of 327 articles were identified and 36 abstracts were included, with studies published between 2012-2019. Strategies including clinician education, electronic medical record alerts, reflex HCV RNA testing, point-of-care testing, multisite (outpatient, inpatient, emergency department, endoscopy suite) initiatives, direct patient solicitation, and utilization of non-physician providers have increased HCV screening rates. However, broad implementation remains less than optimal. Barriers include lack of patient acceptance to screening and engagement in the HCV care cascade. The Veterans Affairs Healthcare System has achieved higher birth cohort screening rates through an integrated approach requiring high-level engagement by leadership and institutional commitment. Multiple strategies for increasing birth cohort screening have been successful, but overall rates of HCV screening remain low. These strategies can inform public health efforts to implement emerging national recommendations for expansion of HCV screening to all U.S. adults age 18 or older.

Acute rheumatic fever (ARF) is an inflammatory disease caused by autoimmune responses to bacterial infection. Rheumatic heart disease (RHD) damages one or more heart valves through recurrent episodes of ARF. We aimed to determine the changes in sensitivity, specificity and predictive values in RHD Jones diagnostic guidelines following the inclusion of echocardiograph as an additional diagnostic tool for RHD.

This is a retrospective cross-sectional study done in the echocardiography center of Al-Fashir teaching hospital. We included a total of 1,103 patients who presented at our hospital and had a diagnosis of RHD, ischemic heart disease or congestive heart disease during 2011–2017.

Among the RHD patients, screening with echocardiography was associated with increases of the sensitivity value, positive predictive value and specificity value by 18.1%, 8.1% and 1%, as compared to their initial diagnoses by Jones criteria alone, which were primarily based on clinical presentations. Mitral stenosis was the most common RHD abnormality, followed by aortic and tricuspid valve regurgitation. North Darfur state was found to have the lowest prevalence of RHD in all geographical parts of Sudan that have been studied. The female to male ratio was 3:1.

Our data highlight the important role of echocardiography in diagnosing RHD complications through improved diagnostic sensitivity, positive predictive value and specificity.

To evaluate the bioequivalence and safety of a generic (or test) sofosbuvir 400-mg tablet versus a brand-named (or reference) sofosbuvir (Sovaldi®) 400-mg tablet in healthy Chinese volunteers under the fasting and fed conditions.

In this single-dose, randomized, open-label, two-sequence, four-period, crossover study, 52 healthy adult Chinese volunteers were enrolled for the fasting (n = 26) and fed (n = 26) conditions. Under each condition, subjects were randomized to receive initial treatment according to either the test-reference-test-reference or the reference-test-reference-test sequence, and then the treatment was switched to the other sequence after a 7-day washout period. Plasma concentrations of sofosbuvir were measured by high-performance liquid chromatography-tandem mass spectrometry. Non-compartmental pharmacokinetic (PK) analysis was performed using Phoenix WinNonlin software to derive PK parameters for sofosbuvir. Adverse events (AEs) were monitored during the study.

All 52 subjects completed the study. The observed PK parameters, including t1/2, Tmax, Cmax, AUC0–t, and AUC0–∞, were similar between the generic and brand-named sofosbuvir products under fasting and fed conditions. The 90% confidence intervals of test/reference ratios for Cmax, AUC0–t and AUC0–∞ were within the bioequivalence acceptance range. One subject experienced an AE while taking the reference product under the fasting condition, whereas six experienced nine AEs (six and three, respectively, while taking the generic and reference products). All AEs were mild.

The generic sofosbuvir is bioequivalent to the brand-named sofosbuvir under both fasting and fed conditions, and the generic sofosbuvir is as safe and well tolerated as the brand-named product in healthy Chinese volunteers.

COVID-19 outbreak in December 2019 has evolved into a world level pandemic. To cope with an emerging pathogen like SARS-CoV-2, there is no vaccine or specific drug available to treat the disease. However, get to know the characters of the onset stage of the new disease may help us to control the spread of COVID-19. This short article aims to introduce COVID-19 briefly, getting you to know the clinical character, the treatment, public procedurals and researches on COVID-19 quickly but comprehensively.

The recent outbreak of 2019 novel coronavirus infection has involved more than 110,000 people and 105 countries. Many efforts have been made to prevent, contain and treat the related disease (named as coronavirus disease 2019). However, many blind spots might not yet receive needed attention. I here discuss eight blind spots that may interest related parties. If these issues remain outstanding, they will likely lead to many severe harms to the public, healthcare providers and the economy. Additional research is therefore needed to better understand and address these blind spots in fighting the outbreak of coronavirus disease 2019.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena. PBC is characterized by high serum levels of anti-mitochondrial antibodies (AMA) and progressive non-suppurative inflammation of small and medium-sized intrahepatic bile ducts, which could lead to cholestasis, liver fibrosis, cirrhosis, and ultimately liver failure. Apoptosis is the main mechanism of programmed cell death and is an important mechanism to regulate and maintain tissue growth and homeostasis. The clearance of apoptotic cells is a highly regulated process, which is essential to avoid the cell contents from flowing out and to limit the immune response to the generated antigens. Here, we provide a brief overview of the role of apoptosis in the pathogenesis of PBC.

This report expounds on the theoretical origin, anatomical basis, and scientific connotations of "liver governs growth", the definition of precancerous changes in the liver and the core mechanism of malignant transformation, as well as the key pathogenesis in traditional Chinese medicine based on the theory that the "liver governs growth". It also summarizes part of the authors' research achievements in intervening in a malignant transformation during precancerous changes in the liver through traditional Chinese medicine. We hope that this paper can provide insights and methods for further exploration in this area.

Hepatocellular carcinoma (HCC) is the most common neoplasm among all primary liver cancers, and hepatitis B virus (HBV) infection is the leading etiology of HCC worldwide. To identify genes significantly associated with poor survival, along with new insight into the underlying mechanisms and therapeutic targets, we conducted a bioinformatics analysis on HBV-related HCC. First, the microarray datasets GSE121248 and GSE55092 were obtained from the Gene Expression Omnibus database, which were screened for genes differentially expressed in cancer and non-cancer tissues in both datasets according to an adjusted p value < 0.05 and |log fold change| > 1.5. A total of 286 differentially expressed genes (79 up-regulated and 207 down-regulated) were selected for function enrichment analyses, including Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The proteinprotein interaction network and modular analysis were constructed by Cytoscape software. Subsequently, KEGG analysis of 42 hub genes was performed, and Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis were used to validate the differential expression profile and survival associations. In addition, the Connectivity Map (CMAP) database was used to predict small-molecules with activity that might reverse the biological state of HBV-related HCC. Collectively, these analyses identified nine hub genes (BUB1, BUB1B, CCNB1, CCNB2, CDC20, CDK1, MAD2L1, PTTG1, TTK) in the cell cycle pathway as candidate targets. Moreover, compounds targeting cell cycle arrest and apoptosis such as apigenin, resveratrol, and chrysin were selected as candidates with potential therapeutic application for HBV-related HCC.