Hepatitis B virus infection of transplanted human hepatocytes causes a biochemical and histological hepatitis in immunocompetent rats

AIM: To characterize the host response to hepatitis B virus (HBV) infection in human hepatocytes transplanted into immunocompetent rodent rats tolerized by, and transplanted with primary human hepatocytes.METHODS: One week after the transplantation, rats were inoculated with HBV, and viral gene expression, replication,and host response was monitored.RESULTS: HBV DNA was detectable in serum for at least 60 days. HBsAg levels rose steadily for 3 weeks postinoculation and then plateaued at a level of about 0.6 pg/mi. HBV RNA was also found in liver at levels that remained constant through the time course. Immunofluorescence revealed clusters of hepatocytes that stained positive for HBcAg. The presence of HBV covalently closed circular DNA (cccDNA) in liver was demonstrated using nuclease digestion of single-stranded DNA followed by PCR. Serum ALT levels rose and reached a peak level of 180 IU/L on day 18, but remained elevated for 60 days. Histology revealed a progressive predominantly mononuclear lobular hepatitis.CONCLUSION: These data indicate that human hepatocytestransplanted into rats rendered tolerant to these cells, when infected by HBV, results in biochemical as well as histological evidence of hepatitis that accompanies viral gene expression,and DNA replication.

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

Machine learning models for predicting non-alcoholic fatty liver disease in the general United States population:NHANES database

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,affecting over 30% of the United States population.Early patient identification using a simple method is highly desirable.AIM To create machine learning models for predicting NAFLD in the general United States population.METHODS Using the NHANES 1988-1994.Thirty NAFLD-related factors were included.The dataset was divided into the training(70%)and testing(30%)datasets.Twentyfour machine learning algorithms were applied to the training dataset.The bestperforming models and another interpretable model(i.e.,coarse trees)were tested using the testing dataset.RESULTS There were 3235 participants(n=3235)that met the inclusion criteria.In the training phase,the ensemble of random undersampling(RUS)boosted trees had the highest F1(0.53).In the testing phase,we compared selective machine learning models and NAFLD indices.Based on F1,the ensemble of RUS boosted trees remained the top performer(accuracy 71.1%and F10.56)followed by the fatty liver index(accuracy 68.8% and F10.52).A simple model(coarse trees)had an accuracy of 74.9% and an F1 of 0.33.CONCLUSION Not every machine learning model is complex.Using a simpler model such as coarse trees,we can create an interpretable model for predicting NAFLD with only two predictors:fasting C-peptide and waist circumference.Although the simpler model does not have the best performance,its simplicity is useful in clinical practice.

Prevalence and risk factors of steatosis and advanced fibrosis using transient elastography in the United States’ adolescent population

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease in children and adolescents.AIM To determine the prevalence and risk factors of steatosis and advanced fibrosis using transient elastography(TE)in the United States’adolescent population.METHODS Using the National Health and Nutrition Examination Survey 2017-2018,adolescent participants aged 13 to 17 years who underwent TE and controlled attenuation parameter(CAP)were included in this study.Forty-one factors associated with liver steatosis and fibrosis were collected.Univariate and multivariate linear regression analysis were used to identify statistically significant predictors.RESULTS Seven hundred and forty participants met inclusion criteria.Steatosis(S1-S3),based on CAP,and advanced fibrosis(F3-F4),based on TE,were present in 27%and 2.84%of the study population,respectively.Independent predictors of steatosis grade included log of alanine aminotransferase,insulin resistance,waistto-height ratio,and body mass index.Independent predictors of fibrosis grade included steatosis grade,non-Hispanic black race,smoking history,and systolic blood pressure.CONCLUSION This study demonstrated a high prevalence of steatosis in the United States’adolescent population.Almost 3%of United States’adolescents had advanced fibrosis.These findings are concerning because a younger age of onset of NAFLD can lead to an earlier development of severe disease,including steatohepatitis,cirrhosis,and liver decompensation.

Identification of Nonalcoholic Fatty Liver Disease following Pancreatic Surgery in a Western Cohort Using a Novel Radiographic Technique

Background and Aims:While traditional risk factors for the development of nonalcoholic fatty liver disease(NAFLD)relate to metabolic syndrome,several Asian studies have suggested a high rate of de novo NAFLD following pancreaticoduodenectomy(PD).The aim of this study is to identify de novo NAFLD after pancreatic surgery and its associated risk factors.Methods:A retrospective cohort of patients at a single center that underwent PD or distal pancreatectomy(DP)over 7 years was identified.Pre-and postoperative contrast-enhanced computed tomography scans of the abdomen were reviewed,including attenuation measurements of the liver,spleen,and muscle.Primary outcomes included hepatic attenuation,liver to muscle ratio(LMR),and liver to spleen ratio(LSR).Results:Of the 96 patients(mean age 64.3)included,70%underwent PD,and 30%underwent DP.The mean LMR decreased significantly from 1.81 to 1.66(p=0.02),noted only in men.No interaction effect with LMR was observed with surgical type,chemotherapy,blood loss,pancreatic enzyme replacement,or transaminases.LMR decreased In 55%of subjects.Conclusions:Increased fatty infiltration,as evidence by decreased LMR,was found among men that underwent PD and DP within a year of surgery.This may be related to weight loss and malabsorption and deserves further investigation.