Background and Aims: Lifestyle (exercise and dietary) modification is the mainstay of treatment for non-alcoholic fatty liver disease (NAFLD). However, there is paucity of data on effect of intensity of exercise in management of NAFLD, and we aimed to study the effect of variable intensities of exercise on NAFLD.

Methods: The study was performed in the Department of Gastroenterology of the SCB Medical College, Cuttack and the Biju Patnaik State Police Academy, Bhubaneswar. The subjects were police trainees [18 in a moderate intensity exercise group (MIG) and 19 in a low intensity exercise group (LIG)] recruited for a 6-month physical training course (261.8 Kcalorie, 3.6 metabolic equivalent in MIG and 153.6 Kcalorie, 2.1 metabolic equivalent in LIG). NAFLD was diagnosed by ultrasonography, with exclusion of all secondary causes of steatosis. All participants were evaluated by anthropometry (weight, height, body mass index (BMI), waist circumference), assessed for blood pressure and biochemical parameters (blood glucose, liver function test, lipid profile, serum insulin), and subjected to transabdominal ultrasonography before and after 6 months of physical training, and the results were compared.

Results: Both the groups had similar BMI, fasting plasma glucose, AST, gamma-glutamyl transpeptidase, insulin, and homeostatic model assessment-insulin resistance (known as HOMA-IR) (p>0.05). However, subjects in the LIG were older and had lower alanine transaminase, higher triglycerides and lower high-density lipoproteins than MIG subjects. There was a significant reduction in BMI (27.0±2.1 to 26.8±2.0; p=0.001), fasting blood glucose (106.7±21.6 to 85.8±19.0; p<0.001), serum triglycerides (167.5±56.7 to 124.6±63.5; p=0.017), total cholesterol (216.8±29.2 to 196.7±26.6; p=0.037), low-density lipoprotein cholesterol (134.6±21.4 to 130.5±21.9; p=0.010), serum aspartate transaminase (39.3±32.2 to 30.9±11.4; p<0.001), serum alanine transaminase (56.6±28.7 to 33.0±11.3; p<0.001) and HOMA-IR (2.63±2.66 to 1.70±2.59; p<0.001) in the MIG. However, changes in these parameters in the LIG were non-significant. Hepatic steatosis regressed in 66.7% of the NAFLD subjects in the MIG but in only 26.3% of the LIG NAFLD subjects (p=0.030).

Conclusions: Moderate rather than low intensity physical activity causes significant improvement in BMI, serum triglycerides, cholesterol, serum transaminases and HOMA-IR, and regression of ultrasonographic fatty change in liver among NAFLD subjects.

Herb-induced liver injuries (HILI) by traditional herbal medicines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in worldwide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from mainland China, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, however, the following recommendations are given: (1) preference of prospective study design with use of the updated RUCAM version; (2) clear separation of HILI cohorts from those of other herbal products or DILI; (3) case series for epidemiology studies should contain many essential data, possibly also as supplementary material; (4) otherwise, preference of single case reports providing individual case data and RUCAM-based causality gradings, and applying liver test threshold values; and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.

Tumor necrosis factor-alpha (TNF-α) is implicated in the process of various autoimmune and inflammatory diseases through binding to its receptor, the tumor necrosis factor receptor. Nowadays, monoclonal anti-TNF-α antibody is used for the treatment of these diseases because it can neutralize TNF-α to block the relevant signaling responsible for the pathogenesis of these diseases. Currently, such antibody-based therapies have been demonstrated to be effective in controlling rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease and ulcerative colitis. Infliximab is the first monoclonal antibody for the treatment of rheumatoid arthritis and has been approved for the intervention of other autoimmune and inflammatory diseases in the clinic. Although infliximab is considered highly efficacious, more so than common medications such as methotrexate and calcipotriol, its potential disadvantages, including loss of response in some patients, drug-related adverse events and particularly high cost, have motivated chemists and researchers to shift towards its biosimilar, CT-P13. CT-P13 has a better tolerance and much less cost, attracting more attention. Here, we summarize the clinical findings of CT-P13 from clinical trials in various diseases.

The daily incidence and deaths of coronavirus disease 2019 (COVID-19) in the USA are poorly understood. Internet search interest was found to be correlated with COVID-19 daily incidence in China, but has not yet been applied to the USA. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the USA.

We extracted COVID-19 daily new cases and deaths in the USA from two population-based datasets, namely 1-point-3-acres.com and the Johns Hopkins COVID-19 data repository. The internet search-interest of COVID-19-related terms was obtained using Google Trends. The Pearson correlation test and general linear model were used to examine correlations and predict trends, respectively.

There were 636,282 new cases and,325 deaths of COVID-19 in the USA from March 1 to April 15, 2020, with a crude mortality of 4.45%. The daily new cases peaked at 35,098 cases on April 10, 2020 and the daily deaths peaked at 2,494 on April 15, 2020. The search interest of COVID, “COVID pneumonia” and “COVID heart” were correlated with COVID-19 daily incidence, with 12 or 14 days of delay (Pearson’s r = 0.978, 0.978 and 0.979, respectively) and deaths with 19 days of delay (Pearson’s r = 0.963, 0.958 and 0.970, respectively). The 7-day follow-up with prospectively collected data showed no significant correlations of the observed data with the predicted daily new cases or daily deaths, using search interest of COVID, COVID heart, and COVID pneumonia.

Search terms related to COVID-19 are highly correlated with the COVID-19 daily new cases and deaths in the USA.

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.