Assessment of nomogram model for the prediction of esophageal variceal hemorrhage in hepatitis B-induced hepatic cirrhosis.

BACKGROUND: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in hepatitis B virus (HBV) -induced cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to find EVs for treatment have complications, contraindications, and high costs. We sought to identify the nomogram models (NMs) as alternative predictions for the risk of EV hemorrhage. METHODS: In this case-control study, we retrospectively analyzed 241 HBV-induced liver cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January 2021 to April 2023. We applied univariate analysis and multivariate logistic regression to assess the accuracy of various NMs in EV hemorrhage. The area under the curve (AUC) and calibration curves of the receiver's operating characteristics were used to evaluate the predictive accuracy of the nomogram. Decision curve analysis (DCA) was used to determine the clinically relevant of nomograms. RESULTS: In the prediction group, multivariate logistic regression analysis identified platelet distribution and spleen length as independent risk factors for EVs. We applied NMs as the independent risk factors to predict EVs risk. The NMs fit well with the calibration curve and have good discrimination ability. The AUC and DCA demonstrated that NMs with a good net benefit. The above results were validated in the validation cohort. CONCLUSION: Our non-invasive NMs based on the platelet distribution width and spleen length may be used to predict EV hemorrhage in HBV-induced cirrhotic patients. NMs can help clinicians to increase diagnostic performance leading to improved treatment measures.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Global burden of hepatitis B attributable to modifiable risk factors from 1990 to 2019: a growing contribution and its association with socioeconomic status.

BACKGROUND: Hepatitis B is a global public health concern, and modifiable risk factors can accelerate progression of this disease. The burden of hepatitis B attributable to modifiable risk factors has not been well evaluated. We aimed to estimate the disease burden of hepatitis B attributable to tobacco, alcohol use, and a high body mass index (BMI) to guide lifestyle interventions in the management of patients with hepatitis B virus (HBV) infection. RESULTS: In 2019, 33.73% of hepatitis B age-standardized deaths and 34.52% of disability-adjusted life-years (DALYs) were attributable to tobacco, alcohol use, and a high BMI. The proportion showed an increasing trend that 28.23% of deaths and 27.56% of DALYs were attributable to the three modifiable risk factors in 1990. The hepatitis B burden attributable to modifiable risk factors was disparate across regions and countries. Countries with a low socioeconomic status have a high burden of hepatitis B owing to modifiable risk factors. Countries with a high-level sociodemographic index also had an increasing burden of hepatitis B attributable to a high BMI. CONCLUSIONS: Lifestyle interventions are warranted in hepatitis prevention strategies and plans of action. Countries with low and middle socioeconomic development should be prioritized, and countries with high socioeconomic development should be aware of the novel challenge of a high BMI-related disease burden.

Development of a novel prognostic assessment model for hepatitis B virus-related acute-on-chronic liver failure based on reexamination results.

Acute-on-chronic liver failure (ACLF) is a common clinical emergency and critical illness with rapid progression and poor prognosis. This study aims to establish a more efficient system for the prognostic assessment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), which will provide a guiding scheme for subsequent treatment and improve the survival rate of patients. Data on 623 patients with HBV-ACLF were recorded. Univariate and multivariate analyses were performed to determine the discriminative abilities of the novel prognostic assessment model in predicting 90-day mortality. The area under the receiver operating characteristic curve was used to evaluate the accuracy of the models. Patients were divided into high- and low-scoring groups based on the best critical values, and survival rates were analyzed using Kaplan-Meier survival analysis and compared by applying log-rank tests. The area under the curve of the new scoring system established using the results of the first reexamination, the results of the first examination, the mean daily change in these results (MDCR) and the results of other first examinations were 0.911 (95% confidence interval [CI]: 0.889, 0.933), 0.893 (95% CI: 0.868, 0.917), and 0.895 (95% CI: 0.871, 0.919), respectively. The final prognostic scoring system established using the results of the first reexamination was chosen as a novel prognostic assessment model, and patients with lower scores (first reexamination results [FRER] score ≤ 3.65) had longer survival times (P < .001). The prognostic scoring system established using the FRER combined with other examination results can better assess the prognosis of HBV-ACLF at 90 days.

Prevalent coinfection and associated factors for Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus in patients submitted to renal replacement therapy: A cross-sectional study of 21 dialysis units in the State of Mexico.

BACKGROUND: Chronic kidney disease (CKD) predispose to viral coinfections in patients submitted to renal replacement therapy (RRT); nevertheless, few reports have been performed to elucidate the current epidemiology within this population in Mexico. AIM: To estimate the prevalence of HBV, HCV, and HIV coinfection and to explore factors associated with prevalent coinfection in patients living with renal failure undergoing to RRT. METHODS: A multicenter cross-sectional recruitment across 21 units at the Mexican Institute of Social Security (IMSS) at the State of Mexico was performed during 2019. A standardized clinical questionnaire was performed to elucidate individual and relatives-related conditions. A treatment facility questionnaire was applied to the chief responsible of each unit to explore treatment facility variables. Serological testing, clinical, biochemical, and anthropometrical parameters were extracted from clinical records. RESULT: In 1,304 patients (57.5% male, mean age 45.5 (SD: 15.6) years, and 95.8% in hemodialysis), the prevalence of any viral coinfection was 3.14% (95% CI: 2.32%-4.23%). The highest viral coinfection prevalence were for HCV, HBV, and HIV, in which men and subjects diagnosed after 2010's had the highest rates. We identify that being submitted to peritoneal dialysis, being treated in a surrogated dialysis center and living with a close relative with prior hepatitis coinfection were associated factors for any viral coinfection. CONCLUSION: In patients submitted to RRT, the prevalence of viral coinfection remains high compared with general population. Screening strategies, medical awareness and targeted public healthcare policies should prioritize better care practices within patients submitted to RRT in Mexico.

Trends in mortality of liver disease due to hepatitis B in China from 1990 to 2019: findings from the Global Burden of Disease Study.

BACKGROUND: Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world's largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO's goal. METHODS: Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B. RESULTS: In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45-5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = -7.63; 95% CI: -8.25, -7.00), cirrhosis and other chronic liver diseases (EAPC = -4.15; 95% CI: -4.66, -3.65), and liver cancer (EAPC = -5.17; 95% CI: -6.00, -4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019. CONCLUSIONS: Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO's goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.

Countdown on hepatitis B elimination by 2030: the global burden of liver disease related to hepatitis B and association with socioeconomic status.

BACKGROUND AND PURPOSE: Hepatitis B virus (HBV) infection causes both acute and chronic liver disease, performing the key driver toward the global elimination of viral hepatitis by 2030. We used data from Global Burden of Disease (GBD) study to quantify the burden of liver disease due to hepatitis B at the global, regional and national levels. METHODS: Annual incident cases and age-standardized incidence rates (ASIRs) of liver disease due to hepatitis B between 1990 and 2019 were collected from GBD study 2019. Percentage changes of incident cases and estimated annual percentage changes (EAPCs) of ASIRs were calculated to quantify their temporal trends. Correlations between EAPC and socio-demographic index (SDI) and universal health coverage index (UHCI) were evaluated by Pearson correlation analyses. RESULTS: Globally, the incident cases of liver disease due to hepatitis B decreased by 4.51% from 84.45 million in 1990 to 80.65 million in 2019 and ASIR decreased by an average of 1.52% (95%CI - 1.66%, - 1.37%) per year in this period. For the spectrum of liver disease due to hepatitis B, ASIR of cirrhosis and other chronic liver diseases increased by an average of 0.13% (95%CI 0.04%, 0.22%) per year in low SDI region and 0.24% (95%CI 0.04%, 0.34%) per year in low-middle SDI region, and ASIR of liver cancer increased by an average of 0.91% (95%CI 0.37%, 1.46%) per year in high SDI region in 1990-2019. Positive correlations of EAPC in ASIR of liver cancer with SDI and UHCI were observed in nations with SDI ≥ 0.7 or UHCI ≥ 70. CONCLUSION: HBV infection remains a global health problem, causing low and low-middle SDI regions with an increasing trend of cirrhosis and other chronic liver diseases, and high SDI region with an increasing trend of liver cancer. Efforts to eliminate hepatitis B by 2030 needs to focus on not only developing regions but also developed regions.

Integrating hepatitis B care and treatment with existing HIV services is possible: cost of integrated HIV and hepatitis B treatment in a low-resource setting: a cross-sectional hospital-based cost-minimisation assessment.

BACKGROUND: Hepatitis B and HIV care share health system challenges in the implementation of primary prevention, screening, early linkage to care, monitoring of therapeutic success and long-term medication adherence. SETTING: Arua regional referral hospital (RRH) and Koboko district hospital (DH), the West Nile region of Uganda. DESIGN: A cross-sectional hospital-based cost minimisation study from the providers' perspective considers financial costs to measure the amount of money spent on resources used in the stand-alone and integrated pathways. DATA SOURCES: Clinic inputs and procurement invoices, budgetary documents, open market information and expert opinion. Data were extracted from 3121 files of HIV and hepatitis B virus (HBV) monoinfected patients from the two study sites. OBJECTIVE: To estimate provider costs associated with running an integrated HBV and HIV clinical pathway for patients on lifelong treatment in low-resource setting in Uganda. OUTCOME MEASURES: The annual cost per patient was simulated based on the total amount of resources spent for all the expected number of patient visits to the facility for HBV or HIV care per year. RESULTS: Findings showed that Arua hospital had a higher cost per patient in both clinics than did Koboko Hospital. The cost per HBV patient was US$163.59 in Arua and US$145.76 in Koboko while the cost per HIV patient was US$176.52 in Arua and US$173.23 in Koboko. The integration resulted in a total saving of US$36.73 per patient per year in Arua RRH and US$17.5 in Koboko DH. CONCLUSION: The application of the integrated Pathway in HIV and HBV patient management could improve hospital cost efficiency compared with operating stand-alone clinics.

Trends in the disease burden of HBV and HCV infection in China from 1990-2019.

OBJECTIVES: This study aimed to reveal the 30-year dynamics of hepatitis B virus (HBV) and hepatitis C virus (HCV) disease burden in China from 1990-2019. METHODS: HBV/HCV data were retrieved from the Global Burden of Disease database. Joinpoint regression was used to examine temporal trends. Age-period-cohort models were applied to evaluate effects of patient age, period, and cohort on HBV/HCV-associated mortality and incidences. RESULTS: A dramatic decrease in the disease burden of HBV was found from 1990-2019, but the disease burden of HCV has remained stable since 2000. Patient age, period, and cohort exerted a significant effect on the diseases burden of HBV and HCV infection. Compared with women, men had a higher risk of HBV/HCV infections as well as HBV/HCV-associated mortality and liver cancer. Overweight, alcohol, tobacco, and drug use were important risk factors associated with HBV/HCV-associated liver cancer. The incidences of HBV- and HCV-associated liver cancer from 2019-2044 are expected to decrease by 39.4% and 33.3%, respectively. CONCLUSION: The disease burden of HBV/HCV infection has decreased in China over the past 30 years, but HBV incidences remain high, especially in men. Effective management of HBV and HCV infections is still needed for high-risk populations.

Analysis of the association between areal socioeconomic deprivation levels and viral hepatitis B and C infections in Japanese municipalities.

BACKGROUND: We investigated the association between municipal socioeconomic deprivation levels and the positivity of hepatitis B surface antigen (HBsAg) and the prevalence of hepatitis C virus (HCV) among individuals who have never participated in hepatitis screening using Japanese national screening data. METHODS: The hepatitis virus screening data analyzed included the 5-year age group-specific number of participants aged 40 years or older, number of HBsAg-positive persons, and number of HCV carriers for each municipality from 2013 to 2017. Principal component analysis was used to derive a socioeconomic deprivation level using the socioeconomic characteristics of municipalities. Bayesian spatial Poisson regression analysis was conducted to investigate the association between the socioeconomic deprivation level and the results of screening. Data on 1,660 municipalities were used in the analysis. RESULTS: The data of 4,233,819 participants in the HBV screening and 4,216,720 in the HCV screening were used in the analysis. A principal component interpreted as level of rurality (principal component 1) and another principal component interpreted as level of low socioeconomic status among individuals (principal component 2) were extracted as the major principal components. Their principal component scores were used as the deprivation levels of municipalities. Spatial regression analysis showed that the deprivation level derived from the sum of the scores of principal components 1 and 2 was significantly and positively associated with HBsAg positivity and HCV prevalence. In addition, the deprivation level derived only from the score of principal component 2 was also significantly and positively associated with the outcomes. Conversely, the deprivation level derived only from the score of principal component 1 was not associated with the outcomes. Moreover, population density was significantly and positively associated with HBsAg positivity and HCV prevalence. CONCLUSIONS: This study suggested that participation in hepatitis virus screening is important and meaningful, particularly for areas with a higher lower socioeconomic level in Japan.

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.

Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein-host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited. METHODS: We conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization's 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis. RESULTS: 163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1-85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9-63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2-80.8); p = 0.001] were independent predictors of cirrhosis. CONCLUSION: Although most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.

Systemic immune-inflammation index predicts postoperative acute kidney injury in hepatocellular carcinoma patients after hepatectomy.

ABSTRACT: The systemic immune-inflammation index (SII) is an independent prognostic predictor of hepatocellular carcinoma (HCC). The present investigation examined whether an association exists between preoperative SII value and postoperative acute kidney injury (pAKI) in HCC patients.The study included 479 hepatitis B virus (HBV)-associated HCC patients undergoing hepatectomy. The SII was calculated as P × N/L, where P, N, and L represent the counts of platelets, neutrophils, and lymphocytes in routine blood test, respectively. After propensity score matching, logistic regression analysis was used to explore independent predictors of pAKI in HCC patients.pAKI was confirmed in 51 patients (10.8%). The average SII value was higher in patients with pAKI than patients without pAKI. After multivariate logistic regression analysis, SII, history of hypertension, and tumor size, among others, were found to be predictors of pAKI. The optimal threshold value of SII for predicting pAKI was found to be 547.84 × 109/L. Multivariate analysis performed after propensity score matching confirmed that SII ≥ 547.84 × 109/L was an independent predictor of pAKI.The preoperative SII qualifies as a novel, independent predictor of pAKI in HCC patients with HBV infection who underwent hepatectomy.

Death certificates compared to SEER-Medicare data for surveillance of liver cancer mortality due to hepatitis B or hepatitis C infection.

Hepatocellular carcinoma (HCC) is often caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. To investigate the completeness of death certificates for recording viral hepatitis in HCC death, we compared the proportion of HCC deaths with hepatitis virus infection reported on death certificates to that reported as claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database among individuals ≥66 years of age. For 2001-2015, we tabulated proportions of HCC deaths with HBV or HCV infection in each database overall, and by demographic factors. To correct for under ascertainment of viral hepatitis-associated HCC on death certificates, we multiplied by the reciprocal ratio of death certificates to SEER-Medicare. Among HCC decedents, HBV infection was reported on 3.6% of death certificates and 17.2% of Medicare claims. For HCV, corresponding proportions were 14.9% and 26.9%. The ratio of HBV-attributable HCC deaths in death certificates to SEER-Medicare remained ~0.21 over time. The ratio of HCV-attributable HCC deaths decreased 22.1% per year, from 0.70 in 2001 to 0.37 in 2003, and increased 4.1% per year, from 0.47 in 2004 to 0.66 in 2015. Following correction, the 2015 mortality rate from death certificate data increased from 0.2 to 0.9 per 100,000 for HBV-attributable HCC and from 2.3 to 3.5 per 100,000 for HCV-attributable HCC. In conclusion, among older Americans dying from HCC, death certificates captured 21% of HBV and 55% of HCV infections compared to Medicare claims. Our results suggest that death certificates provide incomplete data for viral hepatitis-associated HCC surveillance.

The impact of universal hepatitis B vaccine on the trend of liver cancer from the Global Burden of Disease Study 2017.

AIMS: This study aims to assess the trend of hepatitis B virus (HBV)-attributable liver cancer as well as the impact of HBV vaccine on it. METHODS: We retrieved data from Global Burden Disease study to estimate trends of HBV-attributable liver cancer by region and age from 1990 to 2017 and HBV vaccine data from World Health Organization to assess its impact on these trends for children (0-14 years), adolescents and young adults (15-29 years). Change of cancer cases, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were used to quantify the trends of HBV-attributable liver cancer. RESULTS: In this study, reduction in HBV-attributable cancer incident cases was found among children (from 2080 to 1430), adolescents and young adults (from 10 890 to 9090). In terms of ASR, overall reduction was observed globally by an average of -0.45% (95% CI: -0.62 to -0.29) per year in the same period. The highest reduction in ASR was found in adolescents and young adults with EAPC of -3.02 (95% CI: -3.57 to -2.46). Although the ASR has decreased from all the five regions with universal HBV immunization programme, it has increased in the region without universal vaccination and the highest increase was found among children with EAPC of 1.97 (95% CI: 1.71-2.23). CONCLUSION: Significant reduction in HBV-attributable liver cancer among children was mainly because of the universal HBV vaccination. However, the increasing trend of HBV-attributable liver cancer in region without universal HBV vaccination suggested the necessity of introducing universal immunization.

The burden of liver cirrhosis and underlying etiologies: results from the global burden of disease study 2017.

BACKGROUND: To evaluate the pattern and prevalence trends of liver cirrhosis caused by specific etiologies. RESULTS: Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The ASR increased 0.75 per year. The most pronounced increases were found in middle-high and high socio-demographic index (SDI) regions, especially in the Caribbean and Latin America. Among the etiologies, non-alcoholic steatohepatitis (NASH) related liver cirrhosis accounted for 59.46% of the cases. The ASR increased 1.74 per year, and the increase was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol also increased in both sexes and all SDI regions. In contrast, the ASR of liver cirrhosis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) decreased, especially in middle and low-middle SDI regions. CONCLUSIONS: Though the number of people suffering from HBV and HCV decreases, liver cirrhosis is still a major threat to health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continues to grow. Thus, more targeted and specific strategies should be established based on etiology and prevalence trends of liver cirrhosis. METHODS: We collected data based on Global Burden of Disease (GBD) 2017 study. The age standardized prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trends in prevalence by population, etiologies and regions.

Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis.

With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD. This position paper focuses on defining best practices for the detection, monitoring, diagnosis, and management of suspected acute DILI during clinical trials in patients with CLD, including hepatitis C virus (HCV) and hepatitis B virus (HBV), both with and without cirrhosis and NASH with cirrhosis. This is one of several position papers developed by the IQ DILI Initiative, comprising members from 16 pharmaceutical companies in collaboration with DILI experts from academia and regulatory agencies. It is based on an extensive literature review and discussions between industry members and experts from outside industry to achieve consensus regarding the recommendations. Key conclusions and recommendations include (1) the importance of establishing laboratory criteria that signal potential DILI events and that fit the disease indication being studied in the clinical trial based on knowledge of the natural history of test fluctuations in that disease; (2) establishing a pretreatment value that is based on more than one screening determination, and revising that baseline during the trial if a new nadir is achieved during treatment; (3) basing rules for increased monitoring and for stopping drug for potential DILI on multiples of baseline liver test values and/or a threshold value rather than multiples of the upper limit of normal (ULN) for that test; (4) making use of more sensitive tests of liver function, including direct bilirubin (DB) or combined parameters such as aspartate transaminase:alanine transaminase (AST:ALT) ratio or model for end-stage liver disease (MELD) to signal potential DILI, especially in studies of patients with cirrhosis; and (5) being aware of potential confounders related to complications of the disease being studied that may masquerade as DILI events.

Aflatoxin B1 exposure and liver cirrhosis in Guatemala: a case-control study.

OBJECTIVE: In Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B1 (AFB1) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB1 increases the risk of cirrhosis in the absence of viral infection, however, is not clear. DESIGN: Cirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB1 in crude and adjusted models. A sex-stratified analysis was also conducted. RESULTS: The median AFB1 level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression analyses, higher levels of AFB1 was associated with cirrhosis (quintile 5 vs quintile 1, OR: 11.55; 95% CI 4.05 to 32.89). No attenuation was observed with adjustment by sex, ethnicity, hepatitis B virus status, and heavy alcohol consumption. A significantly increasing trend in association was observed in both models (p trend <0.01). Additionally, the cirrhosis-AFB1 association was more prominent among men. CONCLUSIONS: The current study found a significant positive association between AFB1 exposure and cirrhosis. Mitigation of AFB1 exposure and a better understanding of additional risk factors may be important to reduce the burden of cirrhosis in Guatemala.

The assessment of selected MiRNAs profile in HIV, HBV, HCV, HIV/HCV, HIV/HBV Co-infection and elite controllers for determination of biomarker.

BACKGROUND: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. MATERIALS AND METHODS: The expression level of miRNAs was evaluated in 6 group patients, Elite Controller (EC), HIV, HBV, HCV, HIV-HBV-HIV-HCV, and healthy controls using real-time PCR assays. Also, liver enzymes (ALT and AST) and CD4 T cell count was assessed. RESULTS: After adequate normalization, expression level of miRNAs was determined. The expression level of miR-146 in HIV/HCV co-infected patients was the highest in all groups. The miRNAs expression profile was significantly different in patient groups compared to control and EC. Some miRNA was significantly correlated with viral load and CD4 T cell count. CONCLUSIONS: The involvement of the mentioned miRNAs and correlation of these with viral and cellular parameters can justify the clinical outcome of all patient groups. The differentially expressed miRNA profile in patients suggests that miRNAs can be serve as biomarkers for risk of disease progression and differentiation of infections. Moreover, determining the profiles of miRNAs due to involvement of these in the pathogenesis of infection and manipulating these miRNAs could lead to opening a new gate to infection control.