Assessment of Acute Pancreatitis Severity and Prognosis with CT-Measured Body Composition.

OBJECTIVE: The aim of this study was to investigate the possible association of muscle and adipose parameters with the severity and prognosis of patients hospitalized with acute pancreatitis (AP). METHODS: A total of 392 hospitalized patients and 309 controls were enrolled in the study analysis from April 1, 2016, to February 1, 2021. The computed tomography scans of each population were evaluated for muscle and adipose parameters. The effects of parameters on developing moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) were evaluated using univariate and multivariate logistic regression analyses. Associations with disease recurrence and death were analyzed through Cox regression analysis. RESULTS: The AP patients had higher levels of visceral adipose tissue (144.25 vs 97.81 cm2, p < 0.001) and subcutaneous adipose tissue (135 vs 120 cm2, p < 0.001) but lower levels of adipose tissue attenuation (visceral and subcutaneous) and skeletal muscle attenuation (SMA) than the controls (p < 0.05, respectively). Visceral adipose tissue (VAT) and SMA differed significantly with p-values of 0.014 and 0.003 in the different severity groups of AP. In multivariate analysis, VAT and SMA were associated with MSAP or SAP, with odds ratios of 1.003 and 0.973, respectively (95% CI 1.000-1.006, p = 0.041; 95% CI 0.953-0.993, p = 0.010). Cox regression analysis showed that low SMA was strongly associated with an increased mortality in MSAP and SAP patients (HR 10.500, 95% CI 1.344-82.025, p = 0.025). Regression analysis also showed an association of VAT loss of more than 17% with reduced 1-year recurrence of acute pancreatitis (HR 0.427, 95% CI 0.189-0.967, p = 0.041). CONCLUSION: VAT and SMA were influential factors for the severity and prognosis of patients with AP. Patients should proper diet and exercise after discharge to reduce VAT and strengthen muscle function to improve prognosis.

Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models.

The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models.

Innovation for hepatotoxicity in vitro research models: A review.

Many categories of drugs can induce hepatotoxicity, so improving the prediction of toxic drugs is important. In vitro models using human hepatocytes are more accurate than in vivo animal models. Good in vitro models require an abundance of metabolic enzyme activities and normal cellular polarity. However, none of the in vitro models can completely simulate hepatocytes in the human body. There are two ways to overcome this limitation: enhancing the metabolic function of hepatocytes and changing the cultural environment. In this review, we summarize the current state of research, including the main characteristics of in vitro models and their limitations, as well as improved technology and developmental prospects. We hope that this review provides some new ideas for hepatotoxicity research.

Persistently Increased Resting Energy Expenditure Predicts Short-Term Mortality in Patients with Acute-on-Chronic Liver Failure.

OBJECTIVE: Hypermetabolism based on measurements of resting energy expenditure (REE) is suggested to be a potential biomarker for predicting the clinical outcomes of some diseases. We aimed to evaluate the potential value of hypermetabolism for predicting the short-term (28-day) mortality of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: A total of 105 HBV-ACLF patients, 30 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs) were included in this study. The REE was measured using indirect calorimetry in the morning after 8-10 h of fasting. The predicted REE (REEHB) was determined using Harris-Benedict equation. Persistent hypermetabolism was defined as the REE:REEHB ratio > 1.20 at day 1 and day 7 after admission. The severity of liver disease was estimated using the Model for End-Stage Liver Disease (MELD). Clinical and biochemical variables were determined using blood samples ordered upon admission. These variables were compared between nonsurviving and surviving patients who were classified according to the 28-day mortality. RESULTS: The frequency of hypermetabolism at baseline was significantly higher in ACLF patients than that in HCs and CHB patients. Forty-six (43.8%) ACLF patients died within follow-up of 28 days. Persistent hypermetabolism (OR 2.10; 95% CI 1.15-3.69; p = 0.002) and MELD score (OR 1.93; 95% CI 1.47-3.51; p = 0.012) were independent predictive indicators of 28-day mortality. Furthermore, the performance of the 2 variables (persistent hypermetabolism and MELD) together with the area under the receiver operating curve (AUROC: 0.819) was significantly better than that of MELD alone -(AUROC: 0.694) for prediction of short-term mortality (p = 0.014). CONCLUSION: These findings indicate that persistent hypermetabolism is predictive of short-term mortality in this small population.

Current treatment status and barriers for patients with chronic HCV infection in mainland China: A national multicenter cross-sectional survey in 56 hospitals.

Chronic hepatitis C virus (HCV) infection is a serious public health problem worldwide. China, as the country with the largest number of HCV infections in the world, plays a significant role in eliminating hepatitis C. Due to different financial situations and education background, hepatitis C patients take different actions for their disease treatment and management. Therefore, antiviral treatment status should be attached great importance to learn the medical demand of patients. A nationwide, multicenter survey was conducted from July 2015 to June 2016. Of 1798 inpatients and outpatients with chronic HCV from 56 hospitals participated in the survey. Each patient completed the questionnaire with questions about his/her antiviral therapy status, perception of treatment barriers, and expectations for future treatment. In total 1622 patients, including 1241 with chronic hepatitis C, 344 with cirrhosis, and 37 patients with hepatocellular carcinoma, fulfilled data collection requirements and finally were included in analysis. Overall, up to 30.7% of the patients had not or currently does not intend to receive antiviral therapy. The main reason was expecting more potent and well-tolerance medication (31.5%), followed by the fear of interferon related side effects (27.5%). Multiple regression analysis showed that the patient's annual income, the severity of HCV, and comorbidity were independent predictors of not receiving antiviral therapy. The whole patients were expecting more potent and well tolerance medication available soon. In summary, Peg-IFN/RBV treatment regimen cannot meet the need of patients well, and safe and efficient direct-acting antivirals are urgently needed in mainland China.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.

Nationwide survey of specialist knowledge on current standard of care (Peg-IFN/RBV) and barriers of care in chronic hepatitis C patients in China.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. In China, it is a major national health problem that demands nationwide coordinated emphasis on prevention and treatment. To inform these initiatives, a nationwide survey was conducted from January to April 2015 to evaluate the knowledge, awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV specialists across mainland China were recruited. Respondents were asked a series of 30 open-ended single or multiple response and Likert-scale questions about their HCV treatment knowledge, experience, assessment of HCV care status in China, and perceptions about treatment barriers. RESULTS: Sixty percent of the respondents answered incorrectly to more than half of the questions on basic HCV treatment principles. Over half of them incorrectly believed that maintenance therapy should be prescribed for non-responders (72%) and longer treatment duration improved sustained viral response rates (62%), regardless of HCV RNA level changes. Sixty-six percent of them believed that HCV treatment would still be interferon-based therapy in the next 5 years in China. Patient-related barriers, in particular lack of disease awareness, were considered to be the most significant barriers to HCV care. Payer and medical-provider barriers included affordability issues, lack of reimbursement coverage for testing and treatments, and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient and provider education should be carried out to increase awareness. More effective direct-acting antivirals should be made available and affordable in China.

Coverage of different health insurance programs and medical costs associated with chronic hepatitis C infection in mainland China: a cross-sectional survey in 20 provinces.

BACKGROUND: Hepatitis C virus (HCV) imposes a considerable disease burden in China, with at least 10 million people chronically infected. Little is known about the financial impact of the HCV epidemic, nor about the extent to which various forms of insurance are providing HCV patients with financial protection. A cross-sectional multi-site study was conducted to acquire data that will aid policy-makers and other stakeholders in developing effective strategies to address this situation. METHODS: At 29 hospitals across China, inpatients and outpatients with chronic HCV were surveyed about their insurance coverage and medical costs. Percentages, means and medians were calculated, and differences in continuous variables among multiple groups were analyzed using the Kruskal-Wallis test or Wilcoxon two-sample test. RESULTS: Many inpatients (N = 593) and outpatients (N = 523) reported being covered by one of three major types of government health insurance, but 13 % of inpatients and 43 % of outpatients reported having no insurance. Among inpatients, the total median cost per hospitalization per patient was 8212 Renminbi (RMB). The category of expenditure with the highest median cost per hospitalization was Western medicine, followed by lab tests and Chinese medicine. The median cost per hospitalization was far higher for patients who had hepatocellular carcinoma than for those with less severe forms of liver disease. Outpatient antiviral therapy costs ranged from a median of 377 RMB for ribavirin to a median of 37,400 RMB for pegylated interferon-alpha for up to one year of treatment. CONCLUSIONS: For uninsured chronic HCV patients in China, inpatient and outpatient costs may be financially devastating. Research is needed on how different approaches to financing HCV treatment and care might improve health outcomes as well as achieve cost savings by enabling more people to be cured of HCV.

Impact of partial reimbursement on hepatitis B antiviral utilization and adherence.

AIM: To determine the impact of partial reimbursement for antivirals on antiviral utilization and adherence for chronic hepatitis B patients. METHODS: This was a retrospective cohort study. Two separate cohorts were enrolled, including 14163 and 16288 chronic hepatitis B outpatients, respectively. These patients were referred to Beijing You'an Hospital before and after the new partial reimbursement for antivirals, which was implemented on July 1, 2011. Demographic characteristics (including medical insurance status), routine biochemical, virological and serology laboratory test results, and antiviral agents' prescription information were collected from an electronic database. Patients were also defined as new and existing patients according to treatment history. Antiviral utilization, medication possession ratio and persistence rate were calculated and compared among the patients with different characteristics. A questionnaire survey was conducted among 212 randomly sampled outpatients from the same hospital to confirm the validity of the electronic database. Propensity score matching was used to adjust the distribution of patient's characteristics which may influence the antiviral utilization. χ(2) test or ANOVA was adopted and multivariate logistic regression was used to determine the factors associated with antiviral utilization and good adherence. RESULTS: A total of 13364 outpatients from each cohort were enrolled after the propensity score matching. The antiviral utilization rate for the insured patients increased from 57.4% to 75.9% (P < 0.0001) after the reimbursement, and the rate among those who paid out-of-pocket increased from 54.9% to 56.7% (P = 0.028). Approximately 71% of the patients had a medication possession ratio of more than 80% in each cohort before reimbursement. This increased to 79.2% and 73.1% for insured patients and those who paid out-of-pocket, respectively (P < 0.0001). Insured patients and those who paid out-of-pocket had the similar persistence rates before reimbursement. But after reimbursement, insured patients had higher persistence rates than those who paid out-of-pocket at 6 (86.5% vs 81.5%, P < 0.0001), 9 (79.7% vs 69.9%, P < 0.0001), 12 (73.4% vs 61.9%, P < 0.0001), and 15 mo (66.6% vs 53.1%, P < 0.0001). The reimbursement could significantly improve adherence for the insured patients than those who paid out-of-pocket even after adjusting other covariates, with an interaction odds ratio of 1.422 (95%CI: 1.220-1.657, P < 0.0001). The questionnaire survey supported the validity of the electronic database. CONCLUSION: The reimbursement policy shows a positive impact on antiviral utilization as well as adherence for insured chronic hepatitis B patients.

A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan.

Hepatitis C virus (HCV) infection is associated with substantial clinical and economic burden and is an important public health issue in Asia. The objective of this review was to characterize HCV epidemiology and related complications in China, Japan, South Korea and Taiwan. A search of electronic databases and conference abstracts identified 71 potentially relevant articles. Of those, 55 were included in the epidemiology review and 9 in the review of HCV-related complications. HCV prevalence in the general population was 1.6% in China, 0.6-0.9% in Japan, 0.6-1.1% in South Korea and 1.8-5.5% in Taiwan. Prevalence was higher for injecting drug users (48-90%) and those with human immunodeficiency virus coinfection (32-85%) and was lower for blood donors (<1%). Annual incidence of HCV in China was 6.01 per 100,000. HCV genotype 1b was associated with the highest incidence of hepatocellular carcinoma (HCC). Five-year survival for patients with liver cirrhosis was 73.8%, decreasing to 39.2% following liver transplantation; the majority of deaths were attributable to HCC. Limitations were that the majority of studies included in the epidemiology review were small, regional studies conducted in specific populations, and there was an absence of large population-based studies. Thus, estimates may not be representative of the epidemiology of HCV for each country. The prevalence HCV in China and HCV incidence in the Asian region remain largely unknown, and they are likely underestimated. Further epidemiologic and clinical data are needed to provide more precise estimates for use by public health agencies.

Impact of a new reimbursement program on hepatitis B antiviral medication cost and utilization in Beijing, China.

BACKGROUND: Hepatitis B virus (HBV) infection is a significant clinical and financial burden for chronic hepatitis B (CHB) patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011. AIMS: In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization. METHODS: Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You'an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator. RESULTS: Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented. CONCLUSIONS: Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.

A bioelectrical impedance phase angle measuring system for assessment of nutritional status.

Bioelectrical impedance phase angle has been recommended as a tool to assess nutrition state, but there are no measuring devices have been specially designed for hospital residents. In this study, a system was established for the measurement of bioelectrical impedance phase angle. The electrical composition, calculation method and measuring method of this system are presented in this paper. Experiments showed excellent performance of this system in measuring impedance made of resistors and capacitors. The designed system was also used to measure the bioelectrical impedance phase angle of both healthy subjects and patients with malnutrition, and the results demonstrated that the phase angle of patients with malnutrition is lower than that of healthy subjects (P < 0.01 for male and P < 0.05 for female). These results suggest that phase angle has the potential to be a useful tool for the quantitative assessment of nutritional status.

Current challenges and the management of chronic hepatitis C in mainland China.

Despite decreasing prevalence, new cases of hepatitis C in China are increasing recently with growing percentage of patients who are with advanced disease, aging, or not eligible for interferon-based treatments. Hepatitis C infection represents a serious public health burden. This review was based on expert's consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie-Ping Medical Foundation. The literature searches were conducted in PubMed and critical publications in Chinese journals. Data on hepatitis C prevalence, risk factors, viral or host features, and treatment modalities were extracted and reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C to approximately 0.4% in China, partly because of regulation changes to safer medical practices and illegalizing commercial blood donations. Patient demographics evolved from being dominated by former paid blood donors to include intravenous drug users and others. Although hepatitis C genotype 1 is the most common, other genotypes are emerging in prevalence. The current standard of care is interferon-based without direct acting antivirals. However, many patients failed therapy because of high treatment costs, substantial needs to manage side effects, difficulties with treatment monitoring in the rural areas, and growing populations of elderly and cirrhotic patients. The lack of high efficacy therapies with good safety profile and low disease awareness in China resulted in increasing public burden of advanced hepatitis C disease. Despite significant reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community transmissions are still significant. In addition to promoting disease awareness, interferon-free regimens are needed to reduce the public health burden.

A Novel Estimation of the Impact of Treatment with Entecavir on Long-Term Mortality, Morbidity, and Health Care Costs of Chronic Hepatitis B in China.

OBJECTIVES: Health care decision makers are increasingly concerned about the value of chronic hepatitis B (CHB) treatments in China. This analysis aims at estimating the relative value of entecavir as a first-line option at treatment initiation and for different treatment durations from a holistic perspective. METHODS: CHB was simulated by using a Markov disease transition model with disease states based on available natural history data. The model assumed 5-year treatment duration with entecavir, lamivudine, telbivudine, and adefovir based on published clinical data. The speed of disease progression varies by viral load and hepatitis B "e" antigen status. Direct medical costs included medication and management of liver complications. The primary output was the estimated cost savings of entecavir per patient per day versus the comparator. RESULTS: For treatment duration of 5 years and a follow-up period of 30 years, entecavir treatment was translated into specific patient benefit of an estimated cost saving of $2.69 per day compared with no treatment. In addition, long-term usage of entecavir resulted in daily $2.33 and $1.73 cost saving compared with short-term usage (1-year and 2-year, respectively). Among available treatment options in China, entecavir treatment exhibited about $0.90 to $1.81 daily cost saving versus the comparators. The detailed daily cost saving of entecavir is summarized as follows-entecavir versus lamivudine: $1.81, entecavir versus telbivudine: $0.90, entecavir versus adefovir: $2.02, and entecavir versus generic adefovir: $1.37. CONCLUSIONS: Long-term usage of entecavir exhibits the characteristics of a favorable CHB treatment, which translates into economic value as opposed to either no treatment or alternative strategies.

An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus.

BACKGROUND & AIMS: Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We analyzed methods of risk assessment and interventions for MTCT. METHODS: We reviewed 63 articles and abstracts published from 1975-2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. RESULTS: Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6-12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%-30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10(6) copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. CONCLUSIONS: HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients.

AIM: To study and determine the resting energy expenditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were assessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 +/- 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 +/- 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improvement of liver function, the glucose oxidation rate increased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is significantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These results warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.