recently , there has been increasing interest in the development of non - invasive assessment of liver fibrosis . the current  gold however , liver biopsy is an invasive procedure associated with both patient morbidity and , less commonly , mortality . in asia , where chronic hepatitis b is endemic , there is a constant need for physicians to evaluate the severity of underlying fibrosis , so that treatment to retard disease progression can be started for eligible patients . likewise , it is important to identify patients with underlying cirrhosis to screen for varices and hepatocellular carcinoma . because of the high rate of non - acceptance of liver biopsy in asian patients , they are rarely performed . therefore , there is a need for a more acceptable method of assessment of liver fibrosis . liver stiffness measurement using transient elastography has become available as a non - invasive assessment of liver fibrosis . transient elastography determines liver elasticity by measuring the velocity of a low - frequency shear wave passing through the liver . previous studies have shown good correlation between liver stiffness and liver fibrosis , with a auroc of greater than 0.90 for metavir stage 3 fibrosis or greater in patients with hepatitis c , hepatitis c co - infected with human immunodeficiency virus , chronic biliary disease , and other liver diseases [ 15 ] . the diagnostic accuracy of transient elastography for liver fibrosis is supported by a recently published meta - analysis . although an earlier study showed no correlation between disease activity and liver stiffness , more recent studies have shown that liver stiffness appears to be affected by underlying inflammation , as in patients with acute hepatitis flares [ 7 , 8 ] . in the present study , we aim to determine the effect of severe flare of hepatitis b on liver stiffness measurements over a 12-month period . all chronic hepatitis b patients , defined by hepatitis b surface antigen ( hbsag ) positive for more than 6  months , with hepatitis b flare of alt greater than 10  times upper limit of normal ( uln ) , and admitted to queen mary hospital , hong kong , between the period may 2006 and august 2007 , were included . all patients had hbv dna levels > 10 copies / ml . acute hepatitis a and e were excluded by serological testing . none of the patients included had underlying significant alcohol intake as defined by a daily intake of > 20  g / day . patient demographics and laboratory parameters were recorded at the time of liver stiffness measurement , including age , sex , liver biochemistry , hbsag , hepatitis b e - antigen ( hbeag ) , antibody to hbeag ( anti - hbe ) , and serum hbv dna levels . hbv dna was measured using the cobas taqman hbv dna assay ( roche diagnostics , branchburg , nj ) , with a lower detection limit of 60 copies / ml . liver stiffness measurement was performed using the fibroscan ( echosens , paris , france ) . only patients with at least ten valid measurements and a success rate of over 60% were included . this was performed in all patients at the time of admission , 36 , and 12  months after the time of flare . we adopted the value of < 6.0  kpa as normal liver stiffness , as defined by a previous study . three patients were admitted for hepatitis b flare outside the recruitment period ( with the same inclusion and exclusion criteria as listed ) . the necroinflammatory scores and degree of fibrosis were assessed according to the modified hepatic activity index grading and staging system [ 10 , 11 ] . all statistical analyses were performed using the spss version 14.0 ( spss inc , chicago , il ) . chi - square test was used for categorical variables , and fisher s exact test when appropriate . liver stiffness measurement was performed using the fibroscan ( echosens , paris , france ) . only patients with at least ten valid measurements and a success rate of over 60% were included . this was performed in all patients at the time of admission , 36 , and 12  months after the time of flare . we adopted the value of < 6.0  kpa as normal liver stiffness , as defined by a previous study . three patients were admitted for hepatitis b flare outside the recruitment period ( with the same inclusion and exclusion criteria as listed ) . the necroinflammatory scores and degree of fibrosis were assessed according to the modified hepatic activity index grading and staging system [ 10 , 11 ] . all statistical analyses were performed using the spss version 14.0 ( spss inc , chicago , il ) . chi - square test was used for categorical variables , and fisher s exact test when appropriate . five patients were excluded due to inadequate follow - up , and further four patients were excluded due to a success rate of < 60% in any one of their scans at the three different time points . the patient s demographic , baseline laboratory data , and liver stiffness measurements are summarized in table  1.table  1patient demographics and baseline laboratory valuesparametersvaluetotal patients ( n)38  inadequate follow - up5  invalid scans ( success  <  60%)4  final analysis29sex ( male)23 ( 79%)age ( years)44 ( 2069)hbeag - positive16 ( 55%)bilirubin ( mol / l)34 ( 10469)alkaline phosphatase ( u / l)114 ( 56220)ggt ( u / l)159 ( 48540)ast ( u / l)524 ( 2081,678)alt ( u / l)1,464 ( 5942,476)albumin ( g / l)39 ( 2746)prothrombin time ( s)12.8 ( 11.124.6)platelets ( 10  l)185 ( 78313)hbv dna ( copies / ml)100,000,000 ( 646,020640,000,000)liver stiffness measurement ( kpa)16.8 ( 6.947.2)interquartile ratio17% ( 447% )  < 10  kpa7 ( 24% )  1020  kpa10 ( 35% )  > 20  kpa12 ( 41%)continuous variables expressed as median valuesinterquartile ratio  =  interquartile range / liver stiffness . eighty - six percent of patients had ratio 30% patient demographics and baseline laboratory values continuous variables expressed as median values interquartile ratio  =  interquartile range / liver stiffness . eighty - six percent of patients had ratio 30% eleven ( 38% ) patients were asymptomatic with abnormal liver enzymes discovered on regular blood surveillance . eight ( 28% ) patients presented with jaundice , and ten ( 35% ) patients presented with non - specific viral symptoms without jaundice . none of the patients had normal liver stiffness ( < 6.0  kpa ) at the time of hepatitis flare ; the median liver stiffness was 16.8  kpa ( range 6.947.2 ) . twenty - four ( 83% ) patients were treated with oral nucleoside / nucleotide analogues . at 36  months , there was a significant decline in liver stiffness from a median baseline level of 16.8  kpa ( range 6.947.2 ) to 7.9  kpa ( range 4.620.4 ) ; ( p  <  0.001 ) . eight ( 28% ) patients had normalized their liver stiffness results , as defined by a liver stiffness measurement of < 6  kpa , whereas no patients at baseline had normal liver stiffness measurement . patients who normalized their liver stiffness at 36  months had significantly lower liver stiffness at baseline compared to patients with abnormal liver stiffness at 36  months ( 9.0 vs. 20.4  kpa , respectively , p  =  0.021 ) . there was no significant difference in the age , and baseline levels of bilirubin , alt , platelets , albumin , and prothrombin time , between patients with or without normal liver stiffness at 36  months . twenty - six ( 90% ) had normalized their alt , with the remaining three patients only having minimally elevated alt of less than twice the upper limit of normal . the results are summarized in table  2.table  2comparison of liver stiffness and liver biochemistry at baseline , 36 , and at 12  monthsparametersbaseline36  months12  monthstotal bilirubin34 ( 10469)12 ( 439)12 ( 246)alt ( u / l)1,464 ( 5942,476)30 ( 1166)21 ( 1346)albumin ( g / l)39 ( 2746)44 ( 3652)45 ( 3849)liver stiffness ( kpa)16.8 ( 6.947.2)7.9 ( 4.620.4)6.9 ( 3.323.6)continuous variables expressed as median valuesp  <  0.001 comparing liver stiffness value between baseline and 36  monthsp  =  0.039 comparing liver stiffness value between 36 and 12  months comparison of liver stiffness and liver biochemistry at baseline , 36 , and at 12  months continuous variables expressed as median values p  <  0.001 comparing liver stiffness value between baseline and 36  months p  =  0.039 comparing liver stiffness value between 36 and 12  months at 12  months , the median liver stiffness was 6.9  kpa ( range 3.323.6 ) , which was significantly lower when compared to liver stiffness at 36  months after flare ( p  =  0.039 ) . only one patient had hbv dna level > 10 copies / ml ( 101,850  copies / ml ) , and 59% had undetectable hbv dna . five ( 17% ) patients had the diagnosis of liver cirrhosis at 12  months , defined by a liver stiffness value of > 10.3  kpa . baseline factors associated with the diagnosis of cirrhosis at 12  months included a higher alp level ( 164 vs. 107  u / l , respectively , p  =  0.027 ) and liver stiffness ( 40.3 vs. 14.0  kpa , respectively , p  =  0.016 ) , and lower albumin level ( 35 vs. 40 g / l , respectively , p  <  0.001 ) , compared to those patients that did not have cirrhosis . the baseline age , bilirubin , ast , alt , prothrombin time , platelets , and hbv dna levels were not significantly different between these two groups . the median liver stiffness measurements at baseline , 36 , and at 12  months are summarized in fig . 1 . the serial liver stiffness measurements of every individual patient are shown in fig .  2 . 1median levels of bilirubin , alt , and liver stiffness at baseline , 36 and 12  monthsfig . 2distribution of liver stiffness of all patients at baseline , 36 , and at 12  monthsfig . 3median reduction in liver stiffness between baseline and 36 , and between 36 and 12  months median levels of bilirubin , alt , and liver stiffness at baseline , 36 and 12  months distribution of liver stiffness of all patients at baseline , 36 , and at 12  months median reduction in liver stiffness between baseline and 36 , and between 36 and 12  months of the 29 patients , 25 were available for repeat liver stiffness measurement at the time of last follow - up , beyond the 12  months study period , with a median time of 34  months from the time of flares . there was a further decline in liver stiffness of 1.0  kpa ( p  =  0.02 ) between the last follow - up time and at 12  months . a subgroup of 15 patients ( 52% ) was available at week 4 for early follow - up and had liver stiffness measurements performed at this visit . there was a significant decline at 4  weeks compared to baseline ( 8.8 vs. 11.8  kpa , respectively , p  =  0.005 ) . at 4  weeks l ( range 14437 ) , compared to the baseline level of 1,532  u / l ( range 6122476 ) . , there was no difference in the hbv dna levels at 12  months when compared to those patients that did not have an early decline ( 144 vs. 60 copies / ml , p  =  0.17 ) . therefore , early decline in liver stiffness was not predictive of viral suppression after 1  year.fig . 4median liver stiffness at baseline and at 4  weeks ( subgroup analysis of 15 patients ) median liver stiffness at baseline and at 4  weeks ( subgroup analysis of 15 patients ) the baseline parameters and their correlation are summarized in table  3 . the age , hbeag status , levels of alp , ggt , ast and hbv dna did not significantly correlate with liver stiffness . baseline factors which correlated with liver stiffness measurements included bilirubin , alt , albumin , prothrombin time , and platelet levels ( p  =  0.010 , p  =  0.047 , p  =  0.010 , p  <  0.001 and p  =  0.004 , respectively ) . the correlation co - efficient between baseline parameters and liver stiffness at 36  months for bilirubin , alt , albumin , prothrombin time , and platelet levels was 0.346 ( p  =  0.066 ) , 0.220 ( p  =  0.252 ) , 0.458 ( p  =  0.013 ) , 0.474 ( p  =  0.011 ) , and 0.227 ( p  =  0.245 ) , respectively . the correlation co - efficient between baseline parameters and liver stiffness at 12  months for bilirubin , alt , albumin , prothrombin time , and platelet levels was 0.324 ( p  =  0.086 ) , 0.090 ( p  =  0.642 ) , 0.499 ( p  =  0.006 ) , 0.321 ( p =  0.096 ) , and 0.110 ( p  =  0.577 ) , respectively . there were also significant correlations between the liver stiffness measurement and alt levels at 36  months ( correlation coefficient  =  0.449 , p  =  0.014 ) and at 12  months ( correlation coefficient  =  0.458 , p  =  0.016).table  3correlation of baseline parameters with liver stiffnessparameterscorrelation coefficientp valueage0.2210.249hbeag status0.3100.102bilirubin0.4700.010alkaline phosphatase0.1370.478ggt0.3350.110ast0.3530.060alt0.3710.047albumin0.4710.010prothrombin time0.687<0.001platelet0.5320.004hbv dna0.3100.102spearman s correlation coefficient correlation of baseline parameters with liver stiffness spearman s correlation coefficient there was no significant difference in baseline liver stiffness between hbeag - positive and hbeag - negative patients ( 16.8 vs. 16.4  kpa , respectively , p  =  0.942 ) . after 6  months , there was also no significant difference in liver stiffness between hbeag - positive and hbeag - negative patients ( 7.3 vs. 9.6  kpa , respectively , p  =  0.178 ) . there was also no significant correlation with baseline hbv dna with liver stiffness at baseline and at 6  months after flares ( p  =  0.102 and p  =  0.272 , respectively ) . the levels of alt were stratified into groups above 1,000 , 1,500 , and above 2,000  u / l . there was no difference in liver stiffness between patients with alt  >  1,000  u / l and in those with alt <  1,000  u / l ( 20.4 vs. 16.3  kpa , respectively , p  =  0.40 ) , and in patients with alt  > 1,500  u / l compared with alt  <  1,500  u / l ( 23.9 vs. 15.8  kpa , respectively , p  =  0.201 ) . 2,000  u / l compared with those with alt < 2,000  u / l ( 34.3 vs. 14.4  kpa , respectively , p  =  0.022 ) . twenty - four ( 83% ) patients received nucleoside / nucleotide analogues with lamivudine ( 4 patients ) , adefovir ( 2 patients ) , or entecavir ( 18 patients ) . after 3  months , there was no significant difference in median liver stiffness reduction in patients who received antiviral therapy and those that did not ( 7.2 vs. 12.4  kpa , respectively , p  =  0.845 ) . five patients underwent liver biopsy during their inpatient admission at the time of hepatitis b flare . two were from this study population , and three additional patients were admitted outside the recruitment time . the liver stiffness score was much higher than the expected value for the stage of fibrosis observed on histology.table  4liver stiffness , histological activity and stage of fibrosis during severe flarepatientsexagealtliver stiffness ( kpa)necroinflammatory score ( max 18)fibrosis score ( max 6)1m2862914.3412m487596.9323m218998.8614m461,18420.4835m2467334.351necroinflammatory and fibrosis score according to the modified hepatic activity index grading and staging system liver stiffness , histological activity and stage of fibrosis during severe flare necroinflammatory and fibrosis score according to the modified hepatic activity index grading and staging system at 36  months , there was a significant decline in liver stiffness from a median baseline level of 16.8  kpa ( range 6.947.2 ) to 7.9  kpa ( range 4.620.4 ) ; ( p  <  0.001 ) . eight ( 28% ) patients had normalized their liver stiffness results , as defined by a liver stiffness measurement of < 6  kpa , whereas no patients at baseline had normal liver stiffness measurement . patients who normalized their liver stiffness at 36  months had significantly lower liver stiffness at baseline compared to patients with abnormal liver stiffness at 36  months ( 9.0 vs. 20.4  kpa , respectively , p  =  0.021 ) . there was no significant difference in the age , and baseline levels of bilirubin , alt , platelets , albumin , and prothrombin time , between patients with or without normal liver stiffness at 36  months . twenty - six ( 90% ) had normalized their alt , with the remaining three patients only having minimally elevated alt of less than twice the upper limit of normal . the results are summarized in table  2.table  2comparison of liver stiffness and liver biochemistry at baseline , 36 , and at 12  monthsparametersbaseline36  months12  monthstotal bilirubin34 ( 10469)12 ( 439)12 ( 246)alt ( u / l)1,464 ( 5942,476)30 ( 1166)21 ( 1346)albumin ( g / l)39 ( 2746)44 ( 3652)45 ( 3849)liver stiffness ( kpa)16.8 ( 6.947.2)7.9 ( 4.620.4)6.9 ( 3.323.6)continuous variables expressed as median valuesp  <  0.001 comparing liver stiffness value between baseline and 36  monthsp  =  0.039 comparing liver stiffness value between 36 and 12  months comparison of liver stiffness and liver biochemistry at baseline , 36 , and at 12  months continuous variables expressed as median values p  <  0.001 comparing liver stiffness value between baseline and 36  months p  =  0.039 comparing liver stiffness value between 36 and 12  months at 12  months , the median liver stiffness was 6.9  kpa ( range 3.323.6 ) , which was significantly lower when compared to liver stiffness at 36  months after flare ( p  =  0.039 ) . only one patient had hbv dna level > 10 copies / ml ( 101,850  copies / ml ) , and 59% had undetectable hbv dna . five ( 17% ) patients had the diagnosis of liver cirrhosis at 12  months , defined by a liver stiffness value of > 10.3  kpa . baseline factors associated with the diagnosis of cirrhosis at 12  months included a higher alp level ( 164 vs. 107  u / l , respectively , p  =  0.027 ) and liver stiffness ( 40.3 vs. 14.0  kpa , respectively , p  =  0.016 ) , and lower albumin level ( 35 vs. 40 g / l , respectively , p  <  0.001 ) , compared to those patients that did not have cirrhosis . the baseline age , bilirubin , ast , alt , prothrombin time , platelets , and hbv dna levels were not significantly different between these two groups . the median liver stiffness measurements at baseline , 36 , and at 12  months are summarized in fig . 1 . the serial liver stiffness measurements of every individual patient are shown in fig .  2 . 1median levels of bilirubin , alt , and liver stiffness at baseline , 36 and 12  monthsfig . 2distribution of liver stiffness of all patients at baseline , 36 , and at 12  monthsfig . 3median reduction in liver stiffness between baseline and 36 , and between 36 and 12  months median levels of bilirubin , alt , and liver stiffness at baseline , 36 and 12  months distribution of liver stiffness of all patients at baseline , 36 , and at 12  months median reduction in liver stiffness between baseline and 36 , and between 36 and 12  months of the 29 patients , 25 were available for repeat liver stiffness measurement at the time of last follow - up , beyond the 12  months study period , with a median time of 34  months from the time of flares . there was a further decline in liver stiffness of 1.0  kpa ( p  =  0.02 ) between the last follow - up time and at 12  months . a subgroup of 15 patients ( 52% ) was available at week 4 for early follow - up and had liver stiffness measurements performed at this visit . there was a significant decline at 4  weeks compared to baseline ( 8.8 vs. 11.8  kpa , respectively , p  =  0.005 ) . at 4  weeks , the median alt was 103  u / l ( range 14437 ) , compared to the baseline level of 1,532  u / , there was no difference in the hbv dna levels at 12  months when compared to those patients that did not have an early decline ( 144 vs. 60 copies / ml , p  =  0.17 ) . therefore , early decline in liver stiffness was not predictive of viral suppression after 1  year.fig . 4median liver stiffness at baseline and at 4  weeks ( subgroup analysis of 15 patients ) median liver stiffness at baseline and at 4  weeks ( subgroup analysis of 15 patients ) the age , hbeag status , levels of alp , ggt , ast and hbv dna did not significantly correlate with liver stiffness . baseline factors which correlated with liver stiffness measurements included bilirubin , alt , albumin , prothrombin time , and platelet levels ( p  =  0.010 , p  =  0.047 , p  =  0.010 , . the correlation co - efficient between baseline parameters and liver stiffness at 36  months for bilirubin , alt , albumin , prothrombin time , and platelet levels was 0.346 ( p  =  0.066 ) , 0.220 ( p  =  0.252 ) , 0.458 ( p  =  0.013 ) , 0.474 ( p  =  0.011 ) , and 0.227 ( p  =  0.245 ) , respectively . the correlation co - efficient between baseline parameters and liver stiffness at 12  months for bilirubin , alt , albumin , prothrombin time , and platelet levels was 0.324 ( p  =  0.086 ) , 0.090 ( p =  0.642 ) , 0.499 ( p  =  0.006 ) , 0.321 ( p  =  0.096 ) , and 0.110 ( p  =  0.577 ) , respectively . there were also significant correlations between the liver stiffness measurement and alt levels at 36  months ( correlation coefficient  =  0.449 , p  =  0.014 ) and at 12  months ( correlation coefficient  =  0.458 , p  =  0.016).table  3correlation of baseline parameters with liver stiffnessparameterscorrelation coefficientp valueage0.2210.249hbeag status0.3100.102bilirubin0.4700.010alkaline phosphatase0.1370.478ggt0.3350.110ast0.3530.060alt0.3710.047albumin0.4710.010prothrombin time0.687<0.001platelet0.5320.004hbv dna0.3100.102spearman s correlation coefficient correlation of baseline parameters with liver stiffness spearman s correlation coefficient there was no significant difference in baseline liver stiffness between hbeag - positive and hbeag - negative patients ( 16.8 vs. 16.4  kpa , respectively , p  =  0.942 ) . after 6  months , there was also no significant difference in liver stiffness between hbeag - positive and hbeag - negative patients ( 7.3 vs. 9.6  kpa , respectively , p  =  0.178 ) . there was also no significant correlation with baseline hbv dna with liver stiffness at baseline and at 6  months after flares ( p  =  0.102 and p  =  0.272 , respectively ) . the levels of alt were stratified into groups above 1,000 , 1,500 , and above 2,000  u / l . there was no difference in liver stiffness between patients with alt  >  1,000  u / l and in those with alt  <  1,000  u / l ( 20.4 vs. 16.3  kpa , respectively , p  =  0.40 ) , and in patients with alt  >  1,500  u / l compared with alt  <  1,500  u / l ( 23.9 vs. 15.8  kpa , respectively , p  =  0.201 ) . 2,000  u / l compared with those with alt < 2,000  u / l ( 34.3 vs. 14.4  kpa , respectively , p  =  0.022 ) . twenty - four ( 83% ) patients received nucleoside / nucleotide analogues with lamivudine ( 4 patients ) , adefovir ( 2 patients ) , or entecavir ( 18 patients ) . after 3  months , there was no significant difference in median liver stiffness reduction in patients who received antiviral therapy and those that did not ( 7.2 vs. 12.4  kpa , respectively , p  =  0.845 ) . five patients underwent liver biopsy during their inpatient admission at the time of hepatitis b flare . two were from this study population , and three additional patients were admitted outside the recruitment time . the liver stiffness score was much higher than the expected value for the stage of fibrosis observed on histology.table  4liver stiffness , histological activity and stage of fibrosis during severe flarepatientsexagealtliver stiffness ( kpa)necroinflammatory score ( max 18)fibrosis score ( max 6)1m2862914.3412m487596.9323m218998.8614m461,18420.4835m2467334.351necroinflammatory and fibrosis score according to the modified hepatic activity index grading and staging system liver stiffness , histological activity and stage of fibrosis during severe flare necroinflammatory and fibrosis score according to the modified hepatic activity index grading and staging system recently , transient elastography has become available as a new method in the non - invasive assessment of liver fibrosis . although earlier studies had been performed on caucasian patients with chronic hepatitis c , more recent studies have shown transient elastography to be similar in accuracy for asian patients and in patients with chronic hepatitis b [ 1317 ] . initial studies have shown that liver stiffness measurement with transient elastography correlated well with underlying liver fibrosis , with good diagnostic performance [ 14 ] . most of these studies have been performed on patients with chronic hepatitis c , with less available data on chronic hepatitis b. even less data are available with regard to liver stiffness measurement during the time of hepatitis flare . a recent study performed by arena et al .   of 18 patients with acute viral hepatitis [ hepatitis a ( n  =  7 ) , b ( n  =  8) , and c ( n  =  3 ) ] has shown a significant correlation between liver stiffness and serum aminotransferase levels , concluding that liver stiffness measurement is not reliable in the context of acute hepatitis . in that particular study , the timing of liver stiffness measurements was performed with regard to the defined alt levels after an episode of flare , namely at the time when alt halved , and finally at the time when alt was reduced to < 2    uln . in another study performed by sagir et al .   of 20 patients with hepatitis flares [ hepatitis a ( n  =  1 ) , hepatitis b ( n  =  8) , toxic ( n  =  8) , and autoimmune hepatitis ( n  =  3 ) ] , liver stiffness was found to be elevated in the absence of severe fibrosis or cirrhosis during the time of flare . the correlation between alt levels and the liver stiffness measurement was done by pooling the measurements from 20 patients . in contrast to these two previous studies , the current study looks specifically at those patients with acute severe flare of hepatitis b , followed up for 1  year , with liver stiffness measurement performed at specific time points , namely , at the time of the severe flares , 1 , 36 , and 12  months after these flares . we identified several significant factors which correlated with liver stiffness during an acute flare , including higher bilirubin , alt , and prothrombin time , and lower albumin and platelet levels . the baseline alt and platelet levels , however , were not shown to be correlated with liver stiffness at 36 or at 12  months . by contrast , the baseline albumin level was shown to be inversely correlated to liver stiffness at baseline , after 36 , and at 12  months . there was a trend for correlation with baseline bilirubin level and prothrombin time with liver stiffness at 12  months . this suggests that baseline parameters such as bilirubin , prothrombin time , and albumin may indicate underlying pre - existing damage to the liver already and is more predictive of long - term outcome rather than the severity of the alt rise at the time of hepatitis flare . by stratifying the alt levels , a significantly higher liver stiffness measurement was shown only for patients with alt higher than 2,000  u / l . most of the decline in liver stiffness after a severe flare occurs within the first 6  months , with only further minimal reduction from 6 to 12  months . these results suggest that after an acute hepatitis b flare , liver stiffness returns close to its background level by 36  months , with further minimal decline over the next 6  months . this is in keeping with a larger population study of 1,315 chb patients , whereby the median liver stiffness was found to be 6.7  kpa , which is comparable to the value of 6.9  kpa at 12  months after flare in the present study population . although the decline in liver stiffness in our patients may be partly related to reversal of fibrosis with antiviral therapy , it is likely that the major cause of the decline was due to decrease in inflammatory activities . liver stiffness measurements should be performed at least 6  months after resolution of severe flares ( e.g. alt  <  2    uln ) . if the results remain unexpectedly high , we would recommend repeating another scan in a further 6  months time , as we have shown that there is a further significant decline in liver stiffness between 36 and 12  months . moreover , in those patients with a persistently high measurement at 12  months , a further scan is recommended , as in the current study , these patients had further decline in their liver stiffness at the time of last follow - up . this would give a more accurate assessment of the degree of background severe fibrosis or cirrhosis . whether this can be applied to other causes of severe acute flares of hepatitis , such as acute alcoholic hepatitis , autoimmune flares , acute presentation of wilson s disease , drug - related hepatitis , or other viral hepatitis , remains to be determined . the two previous studies , having shown that liver stiffness is elevated during acute hepatitis flares from other causes , including hepatitis a , hepatitis c , toxic hepatitis , and autoimmune hepatitis , will provide strong evidence for this [ 8 , 18 ] . of note , an increased liver stiffness measurement after an episode of severe flare was not predictive of the presence of underlying advanced fibrosis or cirrhosis , as all patients had lowered their liver stiffness at the time of last follow - up . although we have shown that liver stiffness is significantly higher during the time of hepatitis flare , the nature of this elevated liver stiffness remains to be determined . whether the higher measurements reflect truly the increase in fibrosis or reflects the architectural changes associated with necro - inflammatory activity , such as cellular infiltration , tissue necrosis , or tissue edema , is currently unknown . furthermore , there remains the possibility that the higher liver stiffness measurements seen during an acute hepatitis flare may be artefactual , due to higher water content at the time of severe flares , rather than a true increase in liver stiffness . there is likely a complex interplay of matrix metalloproteinases and their inhibitors during the phase of acute viral hepatitis which may influence liver stiffness at the time of inflammation . the true nature of the increased liver stiffness during a hepatitis flare can only be delineated by liver biopsy . we report five biopsies performed at the time of hepatitis b flare , showing a higher liver stiffness value than expected for the stage of fibrosis on histology . in addition , the fact that liver stiffness was significantly reduced by as early as 1  month in our subgroup analysis , and after 36  months from flares , suggests that the increase in liver stiffness is not reflective of underlying fibrosis , and more as a result of inflammation . this is supported by the lack of significant fibrosis on liver histology in the current study despite having an elevated liver stiffness value , and also in a previous study . further studies are required to determine whether liver stiffness is affected by moderate inflammatory activity ( e.g. alt 25 times upper limit of normal ) . in a recently published study , increasing liver stiffness correlated well with even smaller gradients of alt , including < 0.5    uln , 0.51    uln , and 12    uln . however , because of the high area under the receiver operating characteristic curve ( auroc ) already achieved with transient elastography , such small increments in alt are unlikely to affect the accuracy of the test , and smaller increments in liver enzymes may reflect underlying fibrosis rather than inflammation . first , the sample size was small ; however , this is because the overall number of admissions for severe flares of chb is relatively small . despite the small sample size , the study was able to show significant liver stiffness changes over the different time points . second , there were only a limited number of liver biopsies performed , as this is seldomly carried out in patients with well - documented evidence of hepatitis b flares . in addition , over one - third of the patients admitted for severe flares had elevated prothrombin time , precluding percutaneous biopsies . in conclusion , liver stiffness is increased in chronic hepatitis b patients with severe flares , with return to near normal levels by 6  months . we recommend measuring liver stiffness to document liver fibrosis or cirrhosis in patients having severe hepatitis b flares should be postponed to at least 6  months after flare .
backgroundmeasuring liver stiffness is becoming more popular as a non - invasive tool for assessing liver fibrosis.aimto assess the effect of severe hepatitis b flare on liver stiffness and determine factors that correlate with liver stiffness measurements.methodstwenty-nine patients with severe hepatitis b flare ( alt  >  10    upper limit of normal ) were followed up for 1  year . 
 serial transient elastography was performed at the time of flare , 36 , and 12  months after flare.resultsat the time of flare , the median liver stiffness was 16.8  kpa , with no patients having normal liver stiffness ( < 6  kpa ) . 
 there was a significant decrease in liver stiffness from baseline to 36  months ( 16.8 vs. 7.9  kpa , respectively , p  <  0.001 ) , and a further smaller decline from 36 to 12  months ( 7.9 vs. 6.9  kpa , respectively , p  =  0.039 ) . 
 by 12  months , 10 ( 34% ) had normalized their liver stiffness . 
 baseline parameters which correlated with liver stiffness include bilirubin , alt , albumin , prothrombin time and platelet levels ( all p  <  0.05).conclusionliver stiffness was increased in patients with severe hepatitis b flares , with return to near normal levels by 6  months . 
 transient elastography for proper assessment of liver fibrosis should be performed at least 6  months after flare .