***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND AIM Entecavir is a potent inhibitor of both wild-type and lamivudine-resistant hepatitis B virus ( HBV ) with proven clinical efficacy . We conducted a r and omized , double-blind , multicenter study in Japan ( ETV-052 ) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine-refractory chronic hepatitis B infection . METHODS Eighty-four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir ( 41 patients ) or 1 mg entecavir ( 43 patients ) for 52 weeks . RESULTS The proportions of patients achieving the primary end-point ( > or=2 log(10 ) reduction in HBV-DNA from baseline by polymerase chain reaction assay or undetectable HBV-DNA levels [ < 400 copies/mL ] at week 48 ) were 90 % and 93 % for entecavir 0.5 mg and 1 mg , respectively , with 33 % of patients in each dosing group achieving < 400 copies/mL. The mean reduction in HBV-DNA from baseline was 3.58 and 3.75 log(10 ) copies/mL for entecavir 0.5 mg and 1 mg , respectively . High proportions of patients achieved alanine aminotransferase normalization at week 48 ( 0.5 mg 86 % , 1 mg 78 % ) . Histological improvement was observed in most patients ( 0.5 mg 52 % , 1 mg 60 % ) . Virological breakthrough ( increase in HBV-DNA of > or=1 log(10 ) copies/mL from nadir ) was observed in one patient but was not associated with selection of entecavir-associated resistance substitutions . Entecavir was well tolerated , with no patients discontinuing study drug due to adverse events . CONCLUSIONS These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine-refractory chronic hepatitis BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue  to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) Background / Aims : The ideal end point of treatment for chronic hepatitis B virus ( HBV ) infection is sustained off-therapy hepatitis B surface antigen ( HBsAg ) loss with or even without seroconversion to anti-HBs . We investigated the role of adding PEGylated interferon ( PEG IFN ) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance . Patients and Methods : In this r and omized controlled trial , chronic HBV patients who have been receiving tenofovir for > 6 months with HBV viral load < 2000 IU/ml were r and omized into two groups . One group ( add-on therapy ) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir . Patients in the other group received only tenofovir 300 mg orally on a daily basis . Patients in both groups were followed up for a total of two years , and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance . Results : Twenty-three patients were allocated to the PEG IFN and tenofovir ( add-on therapy ) group , and another 25 patients were recruited to the tenofovir monotherapy group . Before r and omization , patients had received tenofovir for 1135 mean days ( range203 to 1542 days ) . One patient ( 4.3 % ) in add-on therapy lost HBsAg and seroconverted . Within two years , mean HBsAg decreased significantly with add-on therapy ( from 4753 IU/ml to 2402 ; P= 0.03 ) ; and it decreased from 5957 IU/ml to 4198 ; P= 0.09 in tenofovir monotherapy group . More patients in the add-on group developed serious side effects , with treatment discontinuation , and dose reductions ( P = 0.3 ) . Conclusion : PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3 % of the patients . Add-on therapy patients had a significant decrease in HBsAg levels in two years ; and no significant decrease in HBsAg levels with the tenofovir monotherapy . With no significant HBsAg clearance , the utility of this combination regimen is question able Abstract Background Long-term tenofovir disoproxil fumarate ( TDF ) treatment for chronic hepatitis B ( CHB ) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 ( 240 weeks ) and no TDF resistance through 6 years ( 288 weeks ) . Aim We assessed the efficacy , safety , and resistance of TDF for up to 7 years ( 336 weeks ) in HBeAg-positive and HBeAg-negative CHB patients . Methods Patients who completed 1 year ( 48 weeks ) of r and omized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years ( 384 weeks ) . Results Of 641 patients initially r and omized , 585 ( 91.3 % ) entered the open-label phase ; 437/585 ( 74.7 % ) remained on study at year 7 . For patients on treatment at year 7 , 99.3 % maintained viral suppression ( HBV DNA < 69 IU/mL ) , 80.0 % achieved serum alanine aminotransferase normalization , and in HBeAg-positive patients , 84/154 ( 54.5 % ) and 25/154 ( 11.8 % ) achieved HBeAg and HBsAg loss , respectively . One/375 ( 0.3 % ) HBeAg-negative patients achieved HBsAg loss . No resistance to TDF was detected through 7 years . During the open-label phase , grade 3/4 drug-related adverse events were uncommon ( 1.0 % ) ; ten ( 1.7 % ) patients had elevation of serum creatinine ≥0.5 mg/dL above baseline . No significant change in bone mineral density was observed from year 4 to year 7 ( week 192 to week 336 ) . Conclusions Long-term TDF treatment was associated with sustained virologic , biochemical , and serologic responses , without  resistance  . TDF treatment was well tolerated , with a low incidence of renal and bone events . These data confirm the safety and efficacy of long-term TDF for CHB BACKGROUND & AIMS We aim ed to compare the viral suppression , safety and rate of drug resistance between besifovir ( a new acyclic nucleotide analogue ) and entecavir . METHODS Treatment-naïve chronic hepatitis B patients receiving besifovir 90 mg ( n=31 ) , 150 mg ( n=28 ) and entecavir 0.5 mg ( n=30 ) were monitored for liver biochemistry , viral serology , HBV DNA levels , development of drug resistance mutations , and adverse events throughout 96 weeks of treatment . RESULTS The mean decline of HBV DNA levels from baseline to week 96 were 5.29 , 5.15 , and 5.67 logs IU/ml for patients receiving besifovir 90 mg , 150 mg and entecavir 0.5 mg , respectively ( p>0.05 ) . Undetectable HBV DNA ( < 20 IU/ml ) were achieved in 80.7 % , 78.6 % , and 80 % ; ALT normalization in 90.3 % , 78.6 % , and 93.3 % ; and loss of HBeAg in 20 % , 21.4 % , and 22.2 % of patients respectively ( all p>0.05 ) . One patient receiving besifovir 90 mg had a virological breakthrough due to drug non-compliance . No patient developed drug resistance mutations . Ten patients had serious adverse events , which were not related to the study medications . The most common side effect related to besifovir was carnitine depletion .  Carnitine supplements were prescribed to 83.9 % and 100 % of patients , who had low carnitine level for any one time during follow-up , receiving besifovir 90 mg and 150 mg respectively . No patient had increased creatinine>0.5 mg/dl from baseline . CONCLUSIONS Besifovir had the same antiviral property as compared to entecavir over 96 weeks of treatment for chronic hepatitis B patients .  Besifovir was well tolerated and also had a good clinical safety profile BACKGROUND & AIMS Long-term treatment with tenofovir disoproxil fumarate ( TDF ) alone , or in combination with emtricitabine ( FTC ) is associated with sustained viral suppression in patients with lamivudine resistant ( LAM-R ) chronic hepatitis B ( CHB ) . METHODS LAM-R CHB patients were r and omised 1:1 to receive TDF 300 mg or FTC 200 mg and TDF 300 mg once daily in a prospect i ve , double blind , study . The proportion of patients with plasma hepatitis B virus ( HBV ) DNA<69IU/ml ( < 400copies/ml ) at week 96 ( primary efficacy endpoint ) was reported previously . Here we present week 240 follow-up data . RESULTS Overall , 280 patients were r and omised to receive TDF ( n=141 ) or FTC/TDF ( n=139 ) , and 85.4 % completed 240weeks of treatment . At week 240 , 83.0 % of patients in the TDF arm , and 82.7 % of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml ( p=0.96 ) . Rates of normal alanine aminotransferase ( ALT ) and normalised ALT were similar between groups ( p=0.41 and p=0.97 respectively ) . Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups , ( p=0.41 and p=0.67 respectively ) . Overall , six patients achieved hepatitis B surface antigen ( HBsAg ) loss and one patient ( FTC/TDF arm ) had HBsAg seroconversion by week 240 . No TDF resistance was observed up to week 240 . Treatment was generally well tolerated , and renal events were mild and infrequent ( ∼8.6 % ) . The mean change in bone mineral density at week 240 was -0.98 % and -2.54 % at the spine and hip , respectively . CONCLUSIONS TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks . LAY SUMMARY The goal of oral antiviral treatment for chronic he 
    Output:
    
The most common AEs in all NAs assessed were abdominal pain/discomfort , nasopharyngitis/upper respiratory tract infections , fatigue , and headache .
In conclusion , treatment of CHB with NAs is safe , with a low incidence of AEs .
Despite the general underst and ing TAF being safer than TDF , the number of patients treated with TAF still is too small in comparison to other NAs to consoli date an accurate safety profile .