Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients

AIM:To evaluate the performance of a novel non-invasive controlled attenuation parameter(CAP)to assess liver steatosis.METHODS:This was a multi-center prospective cohort study.Consecutive patients(aged≥18 years)who had undergone percutaneous liver biopsy and CAP measurement were recruited from three Chinese liver centers.Steatosis was categorized as S0:<5%;S1:5%-33%;S2:34%-66%;or S3:≥67%,according to the nonalcoholic fatty liver disease(NAFLD)activity score.The FibroScan?502 equipped with the M probe(Echosens,Paris,France)was used to capture both CAP and liver stiffness measurement values simultaneously.Receiver operating characteristic curves were plotted,and the areas under the curves were calculated to determine the diagnostic efficacy.The accuracy of the CAP values at the optimal thresholds was defined by maximizing the sum of sensitivity and specificity(maximum Youden index).RESULTS:A total of 152 patients were recruited,including 52(34.2%)patients with NAFLD and 100(65.8%)with chronic hepatitis B(CHB)virus infection.After adjustment,the steatosis grade(OR=37.12;95%CI:21.63-52.60,P<0.001)and body mass index(BMI,OR=6.20;95%CI:2.92-9.48,P<0.001)were found independently associated with CAP by multivariate linear regression analysis.CAP was not influenced by inflammation,fibrosis or aetiology.The median CAP values and interquartile ranges among patients with S0,S1,S2 and S3 steatosis were 211(181-240)dB/m,270(253-305)dB/m,330(302-360)dB/m,and 346(313-363)dB/m,respectively.The cut-offs for the CAP values in all patients with steatosis≥5%,≥34%and≥67%were 253 dB/m,285 dB/m and 310 dB/m,respectively.The areas under the curves were 0.92,0.92and 0.88 for steatosis≥5%,≥34%and≥67%,respectively.No significant differences were found in the CAP values between the NAFLD group and the CHB group in each steatosis grade.CONCLUSION:CAP appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis,but is limited by BMI.

Gut microbiota dysbiosis in patients with nonalcoholic fatty liver disease

BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value <0.01. RESULTS: NAFLD patients harbored lower gut microbiota diversity than healthy subjects did. In comparison to the control group, the Proteobacteria (13.50%) and Fusobacteria (2.76%) phyla were more abundant in NAFLD patients. Additionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, P<0.01). The phylum Bacteroidetes (44.63%) also tended to be more abundant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepatitis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the corresponding Lachnospiraceae family (24.33% vs 14.21%; P<0.01). Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%; P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. The increased level of the genus Blautia, the family Lachnospiraceae, the genus Escherichia_Shigella, and the family Enterobacteriaceae may be a primary contributor to NAFLD progression.

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Etiology and management of liver injury in patients with COVID-19

The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.

Nodular Regenerative Hyperplasia of Liver Mimicking Cirrhosis: a Case Report

A 34-year-old man with no history of any abdominal pain or fatigue was admitted to our hospital in June 2008 due to the cirrhosis found incidentally during a physical examination. Laboratory examination, electrocardiograph, abdominal ultrasonography and magnetic resonance imaging were carried out during his hospitalization. However, according to the results of the above measures, the diagnosis of nodular regenerative hyperplasia of the liver (NRHL) could not be made. The result of electrocardiograph showed there was no sinus bradycardia. The abdominal ultrasonography showed evidence of hepatosplenomegaly, and magnetic resonance imaging showed multiple non-enhancing hepatic nodules. Histologic conifrmation was available by means of liver biopsy and the deifnitive diagnosis of NRHL was conifrmed histologically by liver biopsy. NRHL always presents with signs of portal hypertension with little evidence of obvious liver disease, NRHL may mimick the cirrhosis of liver and be easily confused with cirrhosis of the liver nodules, so liver biopsy should be recommended for correct diagnosis. The clinical, radiological and pathologic features of this case with NRHL was reported in order to familiarize the physicians with its clinical manifestations.

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease

Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers.We compared the severity of fibrosis in patients with different components of metabolic disorders.Based on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced fibrosis.Results:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without MetS.Patients with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced fibrosis.Using these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,respectively.With the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis.With further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.