Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis.

Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups.

Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48.

Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.

Background and Aims: Recent accumulating evidence indicates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF.

Methods: Serum ATX was measured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrhosis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay.

Results: Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Serum ATX ≥ 584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95% confidence interval of 1.106-20.392, p=0.036).

Conclusions: Serum ATX level may be a useful early warning biomarker for ACLF.

Background and Aims: This study serves to revisit the effects of liver transplantation (LT) on employment in an era of improving survival outcomes post-transplant, and to identify areas of improvement in the transplant process to better optimize post-LT employment and patient satisfaction.

Methods: Prospectively, patients who had undergone LT at a single tertiary LT center were surveyed in person and by e-mail. Primary outcomes included employment rate pre- and post-LT, annual salary, weekly hours worked, barriers to re-employment, and patient satisfaction.

Results: Responses were collected and analyzed from 121 patients who underwent LT. Pre-LT, 68 (56.1%) reported full-time employment, 13 (10.7%) part-time employment, and 40 (33.1%) unemployment. Post-LT, 26 (21.4%) reported continued full-time employment, 18 (14.9%) part-time employment, and 77 (63.6%) unemployment. Average weekly work hours decreased post-LT (16.1 h/week vs. 39.9 h/week). Mean annual salaries decreased post-LT (17 earning salary ≥$40,000 vs. 56 earning salary ≥$40,000). These outcomes differed from patient pre-LT expectations, with 81.0% of previously employed patients believing they would return to employment, resulting in decreased patient satisfaction. Patients working physically demanding jobs pre-LT were less likely to return to work. Reasons cited for lack of return to full employment included early fatigue and difficulty regaining physical strength.

Conclusions: Re-employment rates remain low post-LT, which is particularly true for patients working physically active jobs. Fatigue is a significant barrier to re-employment and increased physical rehabilitation post-LT may prove to be beneficial. Patients should be given realistic expectations about return to employment prior to their LT.

Public health interventions have reduced coronavirus disease 2019 (COVID-19) transmission in several countries, but their impacts on COVID-19 epidemics in the USA are unclear. We examined associations of stay-at-home order (SAHO) and face-masking recommendation with COVID-19 epidemics in the USA.

In this quasi-experimental interrupted time-series study, we modeled temporal trends in daily new cases and deaths of laboratory-confirmed COVID-19 cases, and COVID-19 time-varying reproduction numbers in the USA between March 1 and April 20, 2020. In addition, we conducted simulation analyses.

The number of residents under SAHO increased since March 19 and plateaued at 290,829,980 (88.6% of the U.S. population) on April 7. Trends in COVID-19 time-varying reproduction numbers peaked on March 23, further reduced on April 3, and fell below/around 1.0 on April 13. Early-implementation and early-lift of SAHO would reduce and increase COVID-19 epidemics, respectively. Multivariable piecewise log-linear regression revealed the states’ neighboring relationship with New York was linked to COVID-19 daily new cases and deaths. There were two turning points in daily new-case trend, being March 28 (slope-changes = −0.09) and April 3 (slope-changes = −0.09), which appeared to be associated with implementation of SAHO on March 28 (affecting 48.5% of the US population in 22 states and District of Columbia), and face-masking recommendation on April 3, respectively. There were also two turning points in daily new-death trend, being April 9 (slope-changes = −0.06) and April 19 (slope-changes = −0.90).

We identified two turning points of COVID-19 daily new cases or deaths in the USA, which seem to be linked to implementation of SAHO and the Center for Disease Control’s face-masking recommendation.

Diabetes is among the most frequently reported comorbidities in patients with coronavirus disease 2019 (COVID-19) and it represents a strong risk factor for developing severe, critical and fatal forms of COVID-19. The association between diabetes and worse outcome in viral infections is not unexpected, as hyperglycemia is detrimental to the control of viremia and inflammation, and very often linked to accelerated morbidity and mortality in a majority of patients. Understanding the pathophysiological mechanisms underlying the impact of diabetes on COVID-19 progression is now under critical scrutiny in several ongoing investigations, with the ultimate aim of maximizing therapeutic outcomes. On the other hand, there is a new school of thought that COVOD-19 and its devastating ravage on multiple organs could be causally linked to new-onset diabetes. Thus, the threatening new lesson is that there might be a bidirectional relationship between COVID-19 and diabetes. This review is unique in that it summarizes the very recent literature that supports why we should revisit studying virus-induced diabetes in the context of COVID-19.

Background and Aims: Hepatocellular iron accumulation in patients with chronic liver disease has been linked to adverse outcomes. The objective of this study was to identify clinical factors associated with hemosiderosis.

Methods: A total of 103 consecutive liver transplant recipients were identified, in whom liver biopsy had been performed prior to transplantation. Laboratory and clinical data at biopsy and transplant were abstracted from the medical records and hepatocyte iron was graded in the biopsy and explant. The association of change in iron score from biopsy to transplant, with the time interval between these two events, was examined using linear mixed model analysis for repeated measures.

Results: Most subjects had advanced fibrosis (F3-F4) at liver biopsy, which was performed on average about 2.5 years before transplant. Over 80% of patients had no or 1+ hepatocyte iron at biopsy; iron increased between biopsy and transplant in about 40%. The only demographic or clinical feature that correlated with increased iron was the presence of a transjugular intrahepatic portosystemic shunt. Increased iron at transplant was associated with higher serum iron and transferrin saturation at biopsy, and with lower hemoglobin level, greater mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, higher ferritin and model for end-stage liver disease score at transplant.

Conclusions: The development of hemosiderosis in end-stage liver disease is associated with lower hemoglobin levels and alterations in red blood cell indices that are suggestive of hemolysis. These observations suggest that extravascular hemolysis may play a role in the development of secondary iron overload.

Type 1 diabetes mellitus is a chronic autoimmune disease, requiring glucose monitoring and intensive insulin therapy. Its therapeutic management aims to restore normal HbA1C and stabilize prandial and postprandial glucose levels. The burden of self-management of diabetes is high, and the growing requirement for blood glucose measuring devices presents a challenge. Such devices can continuously monitor glucose concentrations and automatically adjust insulin delivery rates, which in turn help to maintain blood glucose within a healthy range. The artificial pancreas system (so-called APS) technology has evolved rapidly over the past few years, capable of providing effective management of diabetes to improve quality of life of the type 1 diabetes mellitus patients. This review discusses the evolution of the APS technology and its progress in the various components: continuous subcutaneous insulin infusion, mathematical model, real-time continuous glucose monitoring, and control algorithms driving closed-loop control systems. The limitations and the proposed future directives are also discussed.

Hepatitis E virus (HEV) is a global health problem, affecting about 20 million people worldwide. There is significant overlap of hepatitis B virus (HBV) and HEV endemicity in many Asian countries where dual infections with HEV and HBV can occur. Though the clinical course of HEV is largely self-limited, HEV superinfection in patients with chronic hepatitis B (CHB) can result in acute exacerbation of underlying CHB. HEV superinfection in patients with CHB-related cirrhosis has been identified as a risk factor for decompensated cirrhosis and an independent predictor of mortality. Whereas acute HEV infection in pregnancy can cause fulminant liver failure, the few studies on pregnant patients with dual HBV and HEV infection have shown a subclinical course. Immunosuppression is a risk factor for the development of chronic HEV infection, which can be managed by decreasing the dose of immune-suppressants and administering ribavirin. Vaccination for HEV has been developed and is in use in China but its efficacy in patients with CHB has yet to be established in the USA. In this review, we appraise studies on dual infection with HEV and HBV, including the effect of HEV superinfection and coinfection in CHB, management strategies used and the role of active vaccination in the prevention of HEV.

The incidence rate and mortality of liver fibrosis caused by various etiologies are high throughout the world. Liver fibrosis, the subsequent cirrhosis and other serious related complications threaten the health of patients and represent a serious medical burden; yet, there is still a lack of approved methods to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. The activation and proliferation of hepatic stellate cells are still the mechanisms of fibrosis that remain the focus of therapeutic research. In recent years, significant progress has been made in the development and applicability of antifibrosis drugs. In this review, we summarize the effectiveness and safety of available antifibrosis drugs utilizing different targets. In addition, some characteristics of antifibrosis drugs in phase II and III trials are introduced in detail.

Microglia activation can cause degeneration of retinal ganglion cells (RGCs). This study aimed to investigate the potential therapeutic effect of minocycline on microglia activation-related degeneration of RGCs in both retinas after unilateral optic nerve crush (ONC) in the left eye of male adult C57BL/6 mice.

First, the primary degeneration of RGCs after unilateral ONC in the left eye and the secondary degeneration of RGCs in the contralateral eye were investigated. Second, microglia activation in both eyes was examined longitudinally at 1, 5 and 14 days post-ONC. Finally, the effects of minocycline treatment on the primary or/and secondary RGC degeneration as well as the function of both retinas (estimated by flash electroretinogram) at 5 days post-ONC were analyzed.

The results indicated that ONC induced the primary RGC degeneration, which was more severe than the secondary RGC degeneration and microglia activation in both eyes. Treatment with minocycline partially inhibited microglia activation, preserved the function of retinas in both eyes, and delayed the secondary degeneration of RGCs in the contralateral retina.

ONC caused RGC degeneration in both eyes of mice. Minocycline treatment delayed the secondary degeneration of RGCs and improved the function of both retinas post-ONC in mice, which were associated with inhibition of microglia activation.

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term “Immunotherapy” is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy.

The lineage of the erythroid cell has been revisited in recent years. Instead of being classified as simply inert oxygen carriers, emerging evidence has shown that they are a tightly regulated in immune potent population with potential developmental plasticity for lineage crossing. Erythroid cells have been reported to exert immune regulatory function through secreted cytokines, or cell-cell contact, depending on the conditions of the microenvironment and disease models. In this review, we explain the natural history of erythroid cells in the liver through a developmental lens, as it offers perspectives into newly recognized roles of this lineage in liver biology. Here, we review the known immune roles of erythroid cells and discuss the mechanisms in the context of disease models and stages. Then, we explore the capability of erythroid lineage as a cell source for regenerative medicine. We propose that the versatile lineage of erythroid cells provides an underappreciated and potentially promising area for basic and translational research in the field of liver disease.

This review discusses the efficiency and sensitivity of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) imaging in comparison to other radiotracers and imaging techniques. It also conveys its impact on the treatment or management of prostate cancer patients. PSMA, observed in almost all prostate cancer cells, is used for staging and treatment, due to its high multiplication in this cancer when compared to normal tissues. PSMA PET/magnetic resonance imaging (MRI) has applications in the management of prostate cancer. Though PSMA PET/MRI has yielded preliminary results, it is still studied as an imaging biomarker for tumor responses. PSMA-PET/CT is known for its highly sensitive resolution, as it lights up only the parts harboring prostate cancer or tumor cells and not any other kind of lesion. Therefore, 68Ga-PSMA-PET imaging is chosen over other variants of 68Ga-PSMA-11, such as 177Lu-PSMA or 225Ac-PSMA, and it is used for its greater ability to detect metastatic sites in patients with biochemical recurrence and low serum prostate-specific antigens values. The efficacy of 68Ga-PSMA PET/CT also allows for estimation of oligometastases, as it supports the design of therapeutic trials in measuring long-term effects in patients. Finally, 68Ga-PSMA PET/CT is effective in identifying recurrence localization and, hence, permits the ability to choose the best therapeutic strategy as early as possible.

In addition to liver injury, elevation of aminotransferases can be caused by strenuous exercise and use of muscle-building and weight-loss supplements. The purpose of this review is to discuss the various mechanisms of elevation of aminotransferases related to body building. A literature review was performed on clinical trials and case reports involving exercise or supplement use and their effects on aminotransferases. Normal aminotransferase levels varied according to gender, age, body mass index, and comorbidities. Strenuous exercise and weight lifting, especially in the unaccustomed, can cause elevated aminotransferases in the absence of liver damage. Supplements such as anabolic steroids, ephedra, and LipoKinetix, amongst others, have also been associated with aminotransferase elevations. The pattern of elevation of aminotransferases is not helpful in distinguishing liver from muscle injury. Other associated muscle enzymes can be useful in making that distinction. To prevent aminotransferase elevations, subjects not accustomed to moderate-high intensity workouts, are recommended to undertake gradual increase in intensity. When causes of liver injury have been ruled out, investigation into bodybuilding, extreme exercise, and supplement use is warranted.

Xia Sang Ju (XSJ) granule, a Chinese drug and herbal tea made up of Prunellae spica (Xia Ku Cao), Mori folium (Sang Ye), and Flos Chrysanthemi Indici (Ye Ju Hua), is commonly used for fever, headache, and sore throat. The underlying pharmacological mechanism of XSJ on hypertension treatment is described here, based on network pharmacology.

The compounds in XSJ were searched using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (commonly known as TCMSP), and the active components, according to oral bioavailability and drug likeness, were screened. Compounds targets were predicted by the SwissTargetPrediction web server, while hypertension targets were collected from the Online Mendelian Inheritance in Man (commonly known as OMIM) and GeneCards databases. The interaction of targets was analyzed by STRING. The compound-compound target network was constructed by Cytoscape. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (commonly known as KEGG) pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery (commonly known as DAVID).

Forty-five active compounds were obtained from 359 ingredients present in the XSJ decoction, corresponding to 237 targets. In addition, 189 genes were found to be related to hypertension, of which 11 overlapped with XSJ targeted by 28 compounds and were thus considered therapeutically-relevant. ESR2 was the most frequent gene targeted by the compounds, while NR3C1 showed the most interaction with other genes. These results revealed that the anti-hypertensive activity of XSJ may directly relate to the regulation of several hypertension-associated biological processes and pathways, such as cellular nitrogen compound biosynthetic process, positive regulation of the nitrogen compound metabolic process, steroid hormone biosynthesis, and aldosterone-regulated sodium reabsorption.

These findings provide a reference for further interpretation of the potential mode of action of XSJ against hypertension and serve as an example for elucidation of the Traditional Chinese Medicine concept of “multiple compounds-multiple targets-multiple effects”.

In recent years, there has been a significant increase in the incidence of peptic ulcer cases among military personnel. It is important for clinicians to identify the risk factors of peptic ulcer and then implement the appropriate prophylactic measures in a timely manner. This study aims to systematically review the risk factors of peptic ulcer in military personnel.

We searched literature from the PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure, and VIP databases up to November 17, 2019. Eligible studies analyzed at least one risk factor of peptic ulcer in military personnel with descriptive or comparative data. The risk factors’ data were then extracted and tabulated.

Of the 1,008 studies initially identified, 11 were eligible for the present study. The total sample size was 29,925 (ranging from 203 to 10,046). The study population included military officers and soldiers, pilots, armed policemen, and firefighters. The most studied risk factor of peptic ulcer was history of smoking (n = 8), followed by high-intensity training (n = 5), mental stress (n = 5), family history of peptic ulcer (n = 4), history of alcohol drinking (n = 4), and use of non-steroidal anti-inflammatory drugs (n = 4).

Several major risk factors of peptic ulcer have been systematically identified, of which some are modifiable. In the future, proper intervention of these modifiable risk factors may be helpful in preventing military personnel from the development of peptic ulcer.