***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 sWe previously reported a highly sensitive method for serum human telomerase reverse transcriptase ( hTERT ) mRNA for hepatocellular carcinoma ( HCC ) . α-fetoprotein ( AFP ) and des-γ-carboxy prothrombin ( DCP ) are good markers for HCC . In this study , we verified the significance of hTERTmRNA in a large scale multi-centered trial , collating quantified values with clinical course . Methods In 638 subjects including 303 patients with HCC , 89 with chronic hepatitis ( CH ) , 45 with liver cirrhosis ( LC ) and 201 healthy individuals , we quantified serum hTERTmRNA using the real-time RT-PCR . We examined its sensitivity and specificity in HCC diagnosis , clinical significance , ROC curve analysis in comparison with other tumor markers , and its correlations with the clinical parameters using Pearson relative test and multivariate analyses . Furthermore , we performed a prospect i ve and comparative study to observe the change of biomarkers , including hTERTmRNA in HCC patients receiving anti-cancer therapies .  Results hTERTmRNA was demonstrated to be independently correlated with clinical parameters ; tumor size and tumor differentiation ( P < 0.001 , each ) . The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4 % for hTERT . hTERTmRNA proved to be superior to AFP , AFP-L3 , and DCP in the diagnosis and underwent an indisputable change in response to therapy . The detection rate of small HCC by hTERTmRNA was superior to the other markers . Conclusions hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage Optimum cutoff levels for plasma des-gamma-carboxy ( abnormal ) prothrombin ( DCP ) and serum alpha-fetoprotein ( AFP ) were determined by analyzing receiver operating characteristic ( ROC ) curves to discriminate between hepatocellular carcinoma ( HCC ) and benign hepatic conditions .  Plasma DCP levels  in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies , while serum AFP levels for both groups were measured by radioimmunoassay . From ROC curves and tangential lines with a slope of 1.0 , the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml , respectively . Lowered cutoff levels of DCP did not improve the sensitivity , in contrast to the increased sensitivity obtained by lowering the specificity of AFP . The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP , justifying these cutoff levels for the differentiation of benign and malignant liver diseases Mortality due to hepatocellular carcinoma ( HCC ) has not improved over the last 20 years . This is in part due to the poor performance of available tumor markers leading to delays in diagnosis . Des-gamma carboxy-prothrombin ( DCP ) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with alpha-fetoprotein ( AFP ) . We conducted a cross-sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center . Four groups were studied : G1 , normal healthy subjects ; G2 , patients with noncirrhotic chronic hepatitis ; G3 , patients with compensated cirrhosis ; and G4 , patients with histologically proven HCC . A total of 207 subjects were enrolled . Both  DCP and AFP levels increased progressively from G1 to G4 , but DCP values had less overlap among the groups than AFP . ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity ( 89 % ; 95 % CI , 77%-95 % ) and specificity ( 95 % ; 95 % CI , 82%-96 % ) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis . The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL , the area under the ROC curves being 0.928 versus 0.810 , respectively ( P = .002 ) . In conclusion , DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease . Prospect i ve studies to evaluate the role of DCP in early HCC are underway Goals We investigated whether measurement of serum levels of the microRNAs ( miRNAs ) miR-16 , miR-195 , and miR-199a , alone or in combination with conventional serum markers , can help to differentiate hepatocellular carcinoma ( HCC ) from chronic liver diseases ( CLDs ) . Background Recent reports suggest a link between aberrant expression of miRNA , and HCC . Study This retrospective analysis was conducted using sera from 105 HCC patients , 107 CLD patients , and 71 normal control subjects . The miRNAs were measured using real-time reverse transcription-polymerase chain reaction . The conventional HCC markers & agr;-fetoprotein ( AFP ) , lens culinaris agglutinin-reactive AFP ( AFP-L3 % ) , and des-&ggr;-carboxyprothrombin ( DCP ) were measured with commercial kits . Results Serum levels of miR-16 and miR-199a were significantly lower in HCC than in CLD patients or control subjects ( P<0.01 ) . As a single marker , miR-16 had the highest sensitivity for HCC , followed by miR-199a , AFP , DCP , AFP-L3 % , and miR-195 . The combination of miR-16 , AFP , AFP-L3 % , and DCP yielded the optimal combination of sensitivity ( 92.4 % ) and specificity ( 78.5 % ) for HCC , overall and when analysis was restricted to patients with tumors size smaller than 3 cm . As a second-line HCC marker , miR-16 yielded positive HCC predictions in 18 of the 26 ( 69.2 % ) HCC patients with negative results on all 3 conventional markers , most of whom had tumors size smaller than 3 cm ; miR-16 was falsely positive in only 12 of 96 ( 12.5 % ) CLD patients . Conclusions The addition of miR-16 to conventional serum markers improved sensitivity and specificity for HCC . Use of miR-16 for second-line testing in cases considered negative on the basis of conventional HCC markers should be explored in larger , prospect i ve studies Background and aims The role of alphafetoprotein ( AFP ) in the diagnosis and surveillance of hepatocellular carcinoma ( HCC ) is getting smaller owing to the advances in imaging modalities . The aims of this study were to assess the diagnostic accuracy of tumor markers in small HCC and to find the optimal cutoff value of each tumor marker for efficient surveillance . Methods Studies in all language s were identified by search ing MEDLINE from 1982 to 2002 . Studies were included when they showed sensitivity and specificity for HCCs 5 cm or smaller and recruited only patients with chronic hepatitis or liver cirrhosis as control . We assessed diagnostic odds ratios ( DORs ) for the evaluation of diagnostic accuracy of tumor markers and positive likelihood ratios ( LRs+ ) to find the optimal cutoff value . DORs and LRs+ were combined according to the r and om effect model . The summary receiver operating characteristics ( ROC ) curve was also assessed . Results Seventeen articles on three tumor markers  — AFP , des-gamma-carboxyprothrombin ( DCP ) , and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3)—were enrolled after full-text evaluation . AFP was inferior to DCP and AFP-L3 in both DOR ( 4.50 vs. 8.16 and 10.50 ) and area under the ROC curve ( 0.647 vs. 0.688 and 0.695 ) . Optimal cutoff values that provide the best LR+ were 200 ng/ml for AFP , 40 mAU/ml for DCP , and 15 % for AFP-L3 . Conclusions Diagnostic accuracy of AFP in small HCC was substantially limited . Surveillance including other tumor markers with optimal cutoff value should be conducted to confirm the efficacy of the policy BACKGROUND & AIMS The outcome of patients with hepatocellular carcinoma ( HCC ) remains poor because of late diagnosis . The aim of this study was to compare the accuracy of alpha-fetoprotein ( AFP ) and des-gamma-carboxy prothrombin ( DCP ) in the early diagnosis of HCC . METHODS Among 1031 patients r and omized in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis ( HALT-C ) Trial , a nested case-control study of 39 HCC cases ( 24 early stage ) and 77 matched controls was conducted to compare the performance of  AFP and DCP . Testing was performed on sera from 12 months prior ( month -12 ) to the time of HCC diagnosis ( month 0 ) . RESULTS The sensitivity and specificity of DCP  at month 0 was 74 % and 86 % , respectively , at a cutoff of 40 mAU/mL and 43 % and 100 % , respectively , at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61 % and 81 % at a cutoff of 20 ng/mL and 22 % and 100 % at a cutoff of 200 ng/mL. At month -12 , the sensitivity and specificity at the low cutoff was 43 % and 94 % , respectively , for DCP and 47 % and 75 % , respectively , for AFP . Combining both markers increased the sensitivity to 91 % at month 0 and 73 % at month 12 , but the specificity decreased to 74 % and 71 % , respectively . Diagnosis of early HCC was triggered by surveillance ultrasound in 14 , doubling of AFP in 5 , and combination of tests in 5 patients . CONCLUSIONS Biomarkers are needed to complement ultrasound in the detection of early HCC , but neither DCP nor AFP is optimal Aim : We conducted this prospect i ve study to eluci date the long‐term outcome and incidence of hepatocellular carcinoma ( HCC ) development after nucleos(t)ide analog ( NA ) treatment in patients with chronic hepatitis B ( CHB ) or cirrhosis BACKGROUND & AIMS Des-gamma-carboxy prothrombin ( DCP ) and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein ( AFP-L3 ) are surveillance markers used to detect hepatocellular carcinoma ( HCC ) in Japan . This study evaluated their utility , alone or in combination , in a North American population . METHODS Patients with hepatitis C virus-related cirrhosis were followed up prospect ively for 2 years . RESULTS Of 372 patients , HCC developed in 34 of 298 who were free of HCC at entry . The overall sensitivity , specificity , and positive and negative predictive values for only AFP ( > 20 ng/mL ) were 61 % , 71 % , 34 % , and 88 % , respectively ; for only AFP-L3 % ( > 10 ) were 37 % , 92 % , 52 % , and 85 % , respectively ; and for only DCP ( > 7.5 ng/mL ) were 39 % , 90 % , 48 % , and 86 % , respectively . Values increased when AFP values were combined with AFP-L3 % and DCP to 77 % , 59 % , 32 % , and 91 % , respectively . Among patients with increases in AFP levels to 20 to 200 ng/mL , AFP-L3 % and DCP were highly specific markers ( 86.6 % and 90.2 % , respectively ) . Of 29 HCC patients with AFP levels less than 20 ng/mL , 13 had increased levels of AFP-L3 % or DCP . Increased alanine aminotransferase levels were associated with increased total AFP but not AFP-L3 % or DCP levels . Both AFP-L3%- and DCP-positive patients showed significant differences in lower cumulative HCC-free rates compared with the overall group ( P < .0001 and P = .0005 , respectively ) . CONCLUSIONS AFP-L3 % and DCP levels have higher correlation values with an absence of HCC , as well as a higher specificity and negative predictive value , than total AFP . Although this combination of markers only marginally improves surveillance for early HCC , it could identify individuals with negative imaging results who would benefit from follow-up evaluation OBJECTIVES : Prospect i ve studies of serum hepatocellular carcinoma ( HCC ) biomarkers in patients with advanced hepatitis C are lacking . The aim of this study was to determine the frequencies and performance of elevated α-fetoprotein ( AFP ) , AFP-L3 , and des-γ-carboxy prothrombin ( DCP ) levels as HCC biomarkers in advanced hepatitis C. METHODS : Patients in the HALT-C Trial were tested every 3 
    Output:
    
Des-gamma-carboxy prothrombin shows more diagnostic accuracy than AFP , especially in diagnosing early stage HCC , and the combination of both markers can not improve the diagnostic accuracy of early stage HCC