Clinical Study Of Chronic Hepatitis B Complicated With Non-alcoholic Fatty Liver

Background and Objective: Both NAFLD and CHB are the most common basic liver diseases leading to cirrhosis and hepatocellular carcinoma.The infection of NAFLD and HBV is the first and second cause of chronic liver disease in China.The two kinds of chronic liver disease often coexist in clinic,however,wether the combination of CHB and NAFLD will influence the progress or outcome of liver disease in cooperation with HBV,and how the two affect each other,there are still many controversies.In this study,the patients with chronic hepatitis B(CHB),non-alcoholic fatty liver disease(NAFLD)and CHB combined with NAFLD were studied.By comparing the clinical biochemical and histopathological findings of three groups,we can clarify the effect of NAFLD combination on disease progression(liver fibrosis,liver inflammation,hepatic steatosis).Comparing the anti-viral therapeutic effects of CHB and CHB combined with NAFLD to determine the effect of CHB combined with NAFLD on the anti-viral treatment.The incidence if tumor in the patients with different groups was further observed.Methods From January 2011 to December 2017,811 patients with liver diseases who were admitted to Shenzhen third people’s Hospital and who were clinically required to undergo liver histopathological examination.Among them,41 cases of NAFLD,103 cases of CHB combined with NAFLD and 630 cases of CHB confirmed by histopathological examination,and 43 of them were simpe CHB patients who were eligible to enter the group.All the enrolled patients were examined for height,weight,ALT,AST,blood lipid four items,liver fibrosis four items,APRI,hepatitis B five items examination.Hepatic steatosis,hepatic fibrosis and liver inflammation were observed in each group.The results were compared between CHB patients and CHB patients with NAFLD who needed antiviral therapy for 12 weeks,24 weeks,48 weeks,and 96 weeks.The progression of different groups of patients to tumor was also observed.Results(1)The comparison of the baseline of clinical biochemical indexes between the three groups of CHB combined with NAFLD and NAFLD and CHB showed that the body mass index(BMI),alanine transaminase(ALT)Aspartate transaminase(AST),glutamyltransferase(GGT),Alkaline phospharase(ALP)and Uric Acid(UA)levels of the group of CHB combinedwith NAFLD were significantly lower than the group of NAFLD(P<0.05),BMI 、 PLT levels of the group of CHB combined with NAFLD were significantly higher than the group of CHB,and thickness of spleen of CHB combined with NAFLD was obviously lower than the group of CHB(P<0.05).(2)Histopathological findings showed that the degree of hepatic steatosis was positively correlated with the degree of liver inflammation in the group of CHB combined with NAFLD(P < 0.01),however,there was no correlation between the degree of steatosis and the degree of hepatic fibrosis(P> 0.05).The degree of hepatic steatosis and hepatic fibrosis between CHB combined with NAFLD group and NAFLD group were significantly different(P < 0.01).In addition,the degree of hepatic fibrosis in CHB combined with NAFLD group was significantly different from that in CHB group(P < 0.01),but the degree of liver inflammation was not significantlydiferent between the two groups.In the group of CHB combined with NAFLD,the number of patients with mild fatty degeneration(F1)accounted for 66%,a few of them(2.9%)had severe fatty degeneration(F3+F4),and mild fibrosis(S1)accounted for(39.8%),a mount of them(60.2%)above S2.In addition,88.3% of the patients had mild inflammation among the patients with NAFLD,34.1% had mild steatosis and 14.6% had severe steatosis,while only a few of them had mild fibrosis above S2(22%),and 78% of them below S2.In CHB patients,76.7% patients had mild inflammation,a few patients had(23.3%)inflammation degree was more than G2,and 97.7% patients had fibrosis degree above S2.(3)Follow up for three months,six months,one year,one and half a year,and two years of antiviral therapy in CHB group and CHB combined with NAFLD group showed that: There was no significant difference in hepatic fibrosis index and inflammatory index between the two groups at 12 weeks after antiviral therapy in CHB combined with NAFLD group(P > 0.05).The decline of ALT and GGT of hepatitis B group were significantly lower than CHB with NAFLD group at 48 weeks(all P < 0.05).At 48 weeks,the level of HBV-DNA in CHB combined with NAFLD group and CHB group was significantly lower than that in pre-treatment group,but the decrease level in CHB group was more significant than that in CHB combined with NAFLD group(P < 0.05).Rates of hepatitis B virus(HBV)DNA clearance in the CHB combined with NAFLD group at 12,24,48,72 and 96 weeks were 0%,18.4%,38.8%,49%,57.1%,respectively,which were all significantly lower than those in CHB group(25.6%,55.8%,79.1%,81.4%,90.7%,X2=14.237,13.961,15.226,10.462,13.03,all P<0.05).The negative conversion rates of HBe Ag in the CHB combined with NAFLD group at 48,96 weeks were 29%,32.3%,which were all no significant differences than those in CHB group(29%,32.3%,X2=3.557,0.035,both P>0.05).At 12 weeks after antiviral therapy,the rate of ALT normalization in CHB combined with NAFLD group and CHB group was 4.1% and 10%,respectively.There was no significant difference in ALT recovery rate between NAFLD group and CHB group(X2=1.099,P= 0.294).Rates of ALT normalization were in the CHB combined with NAFLD group at 24,48,72,96 weeks were 16.3%,36.7%,44.9%,49%,which were all significantly lower than those in CHB group(53.3%,63.3%,83.3%,86.7%,X2=12.049,5.287,11.407,11.375,all P<0.05).(4)Two cases of liver cancer were found in CHB combined with NAFLD group and CHB group.Conclusions(1)The degree of hepatic inflammation in patients with CHB was not aggravated by NAFLD;(2)The combination of NAFLD may be more prone to fibrosis,but the severity of progression is slower than that of group CHB;(3)The combination of NAFLD reduces the antiviral effect of CHB patients.