Nonalcoholic fatty pancreatic disease (NAFPD) is characterized by increased fat accumulation in the pancreas. It is a component of metabolic syndromes and often coexists with nonalcoholic fatty liver disease. A definitive NAFPD diagnosis is closely associated with acute and chronic pancreatitis, type 2 diabetes, pancreatic fibrosis, and pancreatic cancer. Recent research indicates that NAFPD is also closely associated with cardiovascular disease, liver fibrosis, and liver cancer. The prevalence of NAFPD ranges from 11% to 69% and increases with age. Notably, the prevalence of NAFPD among obese children is two-fold greater than among nonobese children, and the high prevalence and complexity of the disease have garnered much attention. Meanwhile, joint efforts and collaborations from multiple disciplines, including hepatopathy, gastroenterology, endocrinology and metabolism, cardiovascular disease, imaging, and pathology, are required to enhance our understanding of NAFPD and fully comprehend its clinical significance. These efforts will also allow further explorations on its pathogenesis, diagnosis, and treatment. Herein, we conducted a literature review on the pathogenesis of NAFPD, and the author's perspectives on key future prospects in NAFPD research are also proposed.

Hepatic veno-occlusive disease (HVOD), also known as hepatic sinusoidal obstruction syndrome (HSOS), is a specific type of hepatic vascular disease. The most common cause of HSOS in Western countries is the pretreatment of bone marrow hematopoietic stem cell transplantation (HSCT). In China, the most common cause is the ingestion of plants containing pyrrolidine alkaloids (PAs). In the case of HSCT-HSOS in Europe and the United States, relevant examinations, warning symptoms, and disease staging standards before and after transplantation have been clarified; however, there is a lack of corresponding imaging standards. In China, because there are no obvious early clinical symptoms and effective diagnostic methods for PA-HSOS, the disease can go undiagnosed or be misdiagnosed, and the lack of clinical staging is not conducive to the guidance of clinical diagnosis and treatment. In this article, we review the etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of HSOS in order to provide a reference for clinicians and researchers and contribute to future efforts aimed at establishing highly specific indicators for the diagnosis and prognosis of this disease.

To investigate the correlations of pathological grade and HBV-DNA level with the occurrence of gallbladder diseases in patients with chronic hepatitis B, and to improve clinicians' understanding of this disease.

A total of 282 inpatients with chronic hepatitis B undergoing liver biopsy in Beijing Youan Hospital, Capital Medical University from January 2014 to April 2017 were enrolled. Data on liver pathological grade, HBsAg, HBeAg, HBV-DNA, and gallbladder disease conditions were retrospectively analyzed, and SPSS 19.0 software was used for statistical analysis.

The incidence of gallbladder diseases in chronic hepatitis B patients were not significantly different among different HBsAg levels, between positive and negative HBeAg, or among different HBV-DNA groups (P>0.05). The higher the G grade and S stage of the liver pathology, the higher the incidence of gallbladder wall thickening, with a statistically significant difference (P<0.05).

Gallbladder wall thickening indicates that the degree of liver fibrosis in chronic hepatitis B patients is relatively high and can be used as one of the indexes to evaluate the progression of chronic hepatitis B.

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.

Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment.

Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy.

Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

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.

Methods: Data from 21 phase III clinical trials were analyzed.

Results: The integrated efficacy analysis included 4,817 patients. Findings showed 97.5% of all included patients with chronic HCV achieved SVR12 in the intention-to-treat population. SVR12 rate was >95% across subgroups of interest. The integrated safety analysis included 4,015 patients. Findings showed that 64.1% of patients reported an adverse event, and <0.1% of patients reported a serious adverse event related to glecaprevir/pibrentasvir.

Conclusions: These results indicate that the 8- or 12-week glecaprevir/pibrentasvir treatment is effective for patients infected with HCV genotypes 1-6 without or with compensated cirrhosis, with good safety profiles, irrespective of treatment-experience. Glecaprevir/pibrentasvir is a good option for patients with human immunodeficiency virus/HCV coinfection and comorbid HCV and severe renal impairment.

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.

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.

Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge.

Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed.

Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p<0.01). Moreover, the fatality rate was higher in patients with cholestasis than those without cholestasis (relative risk=2.182, p<0.05). Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge.

Conclusions: LD at early disease stage elevates the risk of death of COVID-19 patients. COVID-19-associated LD does not recover completely by 14 days after discharge.

Background and Aims: To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carcinoma, after transcatheter arterial chemoembolization (TACE).

Methods: This study included 101 patients treated with conventional or drug-eluting beads TACE between the years of 2001 and 2013. Semi-automated 3D quantification software was used to segment and calculate the enhancing tumor volume (ETV) of the liver with and without bias-field correction on multi-phasic contrast-enhanced MRI before and 1-month after initial TACE. ETV (expressed as cm3) at baseline imaging and the relative change in ETV (as % change, ETV%) before and after TACE were used to predict response and survival, respectively. Statistical survival analyses included Kaplan-Meier curve generation and Cox proportional hazards modeling. Q statistics were calculated and used to identify the best cut-off value for ETV to separate responders and non-responders (ETV cm3). The difference in survival was evaluated between responders and non-responders using Kaplan-Meier and Cox models.

Results: MR bias field correction correlated with improved response calculation from baseline MR as well as survival after TACE; using a 415 cm3 cut-off for ETV at baseline (hazard ratio: 2.00, 95% confidence interval: 1.23-3.26, p=0.01) resulted in significantly improved response prediction (median survival in patients with baseline ETV <415 cm3: 19.66 months vs. ≥415 cm3: 9.21 months, p<0.001, log-rank test). A ≥41% relative decrease in ETV (hazard ratio: 0.58, 95%confidence interval: 0.37-0.93, p=0.02) was significant in predicting survival (ETV ≥41%: 19.20 months vs. ETV <41%: 8.71 months, p=0.008, log-rank test). Without MR bias field correction, response from baseline ETV could be predicted but survival after TACE could not.

Conclusions: MR bias field correction improves both response assessment and accuracy of survival prediction using whole liver tumor enhancement analysis from baseline MR after initial TACE in patients with infiltrative hepatocellular carcinoma.

L-theanine (L-THE) is a green tea-derived amino acid, consumed for its many benefits, including improved cardiovascular health, anxiolytic effects, antioxidant properties, and its effect on instigating a state of relaxed alertness. The aim of this clinical trial is to evaluate the effectiveness of the amino acid L-THE embedded in functional food whey protein mango sorbet, its related stress effects on physiological responses, state of alertness, and focus, and the accuracy of eye movements post-consumption.

Twenty-one healthy males, aged 18–65, will be recruited for this study. Participants will be required to consume a mango sorbet (without L-THE) and mango sorbet containing 0.2 g of L-THE and a placebo or 0.2 g pure L-THE within a capsule, after an overnight fast. L-THE exerts its effects 30–50 minutes post consumption, lasting up to 90 minutes. Participants will perform a series of visual functional tests, including habitual visual acuity, contrast sensitivity and measurements of saccadic eye movements after the consumption of the food products at 15-minute intervals to measure their state of alertness and fatigue. Salivary cortisol will be measured every 30 minutes; blood pressure, heart rate and heart rate variability responses will also be measured every 10 minutes.

The use of L-THE as a functional additive may provide potential therapeutic stress benefits when consumed alongside food products. The results of this protocol study will ultimately determine whether L-THE embedded within mango sorbet at physiologically relevant levels can alter the stress response and exhibit its effect on eye fatigue and concentration.

Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC).

Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed.

Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival.

Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.

Background and Aims: With the availability of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection and changing liver disease etiology for liver transplantation (LT), data on the changes in LT recipient population in the DAA era are scanty.

Methods: The United Network for Organ Sharing (UNOS) registry (01/2007 to 06/2018) was used to develop a retrospective cohort of LT recipients for HCV, alcohol-associated liver disease (ALD), and non-alcoholic steatohepatitis (NASH). LT recipients in the DAA era (2013-2018) were compared with those in the pre-DAA era (2007-2012) era for recipient characteristics. Chi-square and analysis of variance were the statistical tests used for categorical and continuous variables, respectively.

Results: Of 40,309 LT recipients (21,110 HCV, 7586 NASH, and 11,713 ALD), the 21,790 in the DAA era (9432 HCV, 7240 ALD, and 5118 NASH) were more likely to be older, female, obese, diabetic, have acute-on-chronic liver failure with a higher model for end-stage liver disease score, receive grafts with a lower donor risk index, and have waited on the LT list for a shorter period compared with their pre-DAA era counterparts. Specific to ALD, LT recipients with alcohol hepatitis were more likely to be younger at the time of LT. Of 9895 LT recipients with hepatocellular carcinoma, recipients in the DAA era were observed to have a higher proportion of HCV (43% vs. 32%, p<0.001), a lower proportion of ALD (9% vs. 12%, p<0.001), and no change for NASH (13% vs. 13%, p=0.9) compared with the pre-DAA era. Within the hepatocellular carcinoma population, LT recipients in the DAA era were older, diabetic, and waited on the LT list longer compared with their pre-DAA counterparts.

Conclusions: Along with changing liver disease etiology in the DAA era, the LT recipient population demographics, comorbidities, liver disease severity, and graft quality are changing. These changes are relevant for future studies, immunosuppression, and post-transplant follow-up.

In this review, we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C, specifically sofosbuvir/velpatasvir (Epclusa®), sofosbuvir/velpatasvir/voxilaprevir (Vosevi®), glecaprevir/pibrentasvir (Maviret®), and elbasvir/grazoprevir (Zepatier®). We searched MEDLINE (1948-January 2020), Embase (1964-January 2020), Google, and GoogleScholar using the terms pharmacokinetics, drug interaction, drug metabolism, sofosbuvir, velpatasvir, Epclusa, voxilaprevir, Vosevi, glecaprevir, pibrentasvir, Maviret, elbasvir, grazoprevir, and Zepatier, from inception to January 13, 2020. The search was limited to randomized controlled trials, in vitro studies, prospective and retrospective human studies, drug monographs, abstracts, and conference proceedings. All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted. Numerous clinically relevant drug-drug interactions (DDIs) were identified with the newer generation DAAs and commonly prescribed drugs. NS3/4A protease inhibitors are more likely to be involved in DDIs, followed by NS5A inhibitors and NS5B polymerase inhibitor. The majority of clinically relevant DDIs are predictable, according to known pharmacokinetic, pharmacodynamics, and physicochemical properties of DAAs; however, in select cases, unpredictable DDIs do occur. As expected, many drug interactions exist between newer generation DAAs and commonly prescribed medications. While the majority of clinically relevant interactions are predictable, many require therapeutic dose adjustment or careful selection of non-interacting drugs. In select cases, severe and unpredictable drug interactions can occur. Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

Perioperative neurocognitive disorder is a decline in cognitive function of patients after anesthesia and surgery. It seems to be a comprehensive effect of the combination of psychological state before the operation, neurotoxicity of narcotic drugs, inflammation caused by the operation, and sleep deprivation after surgery. The glymphatic pathway is a newly discovered system that clears metabolic waste from the brain. The clearing efficiency of the glymphatic pathway can be influenced by sleep deprivation, some narcotic drugs (like dexmedetomidine and ketamine), and neuroinflammation. We hypothesize that the glymphatic system may play a pivotal role in the occurrence and development of perioperative neurocognitive disorder.

Nonalcoholic fatty liver disease (NAFLD) is a complex clinical entity which can be secondary to many other diseases including hypothyroidism, characterized by lowering of thyroid hormones and increased thyroid stimulating hormone (TSH). A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity, even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications. In addition, a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment, currently in phase 3 clinical trials. In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment, specifically thyroid hormone receptor (THR) agonist and its metabolites.