***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 
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    ***EXAMPLES*** 
    Input: PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents UNLABELLED The prognosis of untreated patients with hepatocellular carcinoma ( HCC ) is heterogeneous , and survival data were mainly obtained from control arms of r and omized studies . Clinical practice data on this topic are urgently needed , so as to help plan studies and counsel patients . We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group .  Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer ( BCLC ) classification . We also assessed the main demographic , clinical , and oncological determinants of survival in the subgroup of patients with advanced HCC ( BCLC C ) . Advanced ( BCLC C : n = 138 ; 23.0 % ) and end-stage HCC ( BCLC D ; n = 210 ; 35.0 % ) represented the majority of patients . Overall median survival was 9 months , and the principal cause of death was tumor progression ( n = 279 ; 46.5 % ) . Patients ' median survival progressively and significantly decreased as BCLC stage worsened ( BCLC 0 : 38 months ; BCLC A : 25 months ; BCLC B : 10 months ; BCLC C : 7 months ; BCLC D : 6 months ; P < 0.0001 ) . Female gender ( hazard ratio [ HR ] = 0.55 ; 95 % confidence interval [ CI ] = 0.33 - 0.90 ; P = 0.018 ) , ascites ( HR = 1.81 ; 95 % CI = 1.21 - 2.71 ; P = 0.004 ) , and multinodular ( > 3 ) HCC ( HR = 1.79 ; 95 % CI = 1.21 - 2.63 ; P = 0.003 ) were independent predictors of survival in patients with advanced HCC ( BCLC C ) . CONCLUSION BCLC adequately predicts the prognosis of untreated HCC patients . In untreated patients with advanced HCC , female gender , clinical decompensation of cirrhosis , and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies This r and omized , controlled trial assessed the effect of transarterial embolization ( TAE ) ( without associated chemotherapy ) on the survival of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Eighty consecutive patients were r and omized to treatment with embolization ( Group A , n = 40 ) , or to symptomatic treatment ( Group B , n = 40 ) , there being no differences between both groups regarding the degree of liver function impairment and tumor stage . Eighty‐two percent of the patients presented a self‐limited postembolization syndrome , without treatment‐related mortality . Fifty‐five percent of the treated cases exhibited a partial response , which result ed in a lower probability of tumor progression during follow‐up ( 57 % vs. 77 % at 1 year ; P < .005 ) . However , after a median follow‐up of 24 months ( 30 deaths in each group ) , there are no differences in survival ( Group A : 49 % and 13 % ; Group B : 50 % and 27 % , at 2 and 4 years , respectively ; P = .72 ) . The absence of differences was maintained even when dividing patients according to Child‐Pugh 's grade , Okuda stage , or performance status test ( PST ) . Furthermore , there were no differences in the probability of complications or in the need of hospital admissions . In conclusion , TAE has a marked antitumoral effect associated to a slower growth of the tumor , but it does not improve the survival of patients with nonsurgical HCC OBJECTIVES : Chronic liver disease ( CLD ) is an important cause of morbidity and mortality , but the epidemiology is not well described . We conducted prospect i ve population -based surveillance to estimate newly diagnosed CLD incidence , characterize etiology distribution , and determine disease stage . METHODS : We identified cases of CLD newly diagnosed during 1999–2001 among adult county residents seen in any gastroenterology practice in New Haven County , Connecticut ; Multnomah County , Oregon ; and Northern California Kaiser Permanente Medical Care Program ( KPMCP , Oakl and , California [ total population 1.48 million ] ) . We defined CLD as abnormal liver tests of at least 6 months ' duration or pathologic , clinical , or radiologic evidence of CLD . Consenting patients were interviewed , a blood specimen obtained , and the medical record review ed . RESULTS : We identified 2,353 patients with newly diagnosed CLD ( 63.9 cases/100,000 population ) , including 1,225 hepatitis C patients ( 33.2 cases/100,000 ) . Men aged 45–54 yr had the highest hepatitis C incidence rate ( 111.3/100,000 ) . Among 1,040 enrolled patients , the median age was 48 yr ( range 19–86 yr ) . Hepatitis C , either alone ( 442 [ 42 % ] ) or in combination with alcohol-related liver disease ( ALD ) ( 228 [ 22 % ] ) , accounted for two-thirds of the cases . Other etiologies included nonalcoholic fatty liver disease ( NAFLD , 95 [ 9 % ] ) , ALD ( 82 [ 8 % ] ) , and hepatitis B ( 36 [ 3 % ] ) . Other identified etiologies each accounted for <3 % of the cases . A total of 184 patients ( 18 % ) presented with cirrhosis , including 44 % of patients with ALD . CONCLUSIONS : Extrapolating from this population -based surveillance network to the adult U.S. population , approximately 150,000 patients with CLD were diagnosed in gastroenterology practice s each year during 1999–2001 . Most patients had hepatitis C ; heavy alcohol consumption among these patients was common . Almost 20 % of patients , an estimated 30,000 per year , had cirrhosis at presentation . These results provide population -level baseline data to evaluate trends in identification of patients with CLD in gastroenterology practice BACKGROUND & AIMS The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries . Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years . METHODS Four hundred and two patients with compensated HCV-related cirrhosis were prospect ively recruited in a tertiary care academic center . At the time of admission , patients were stratified as compensated ( absence [ stage 1 ] or presence [ stage 2 ] of esophageal varices ) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates . RESULTS Among 402 subjects , 294 were categorized as stage 1 and 108 as stage 2 . Over a median of 176 weeks , 42 deaths occurred ( 10 % ) , of which 30 were considered liver-related ( 7 % ) and 12 non-liver-related ( 3 % ) ; eight individuals ( 2 % ) underwent liver transplantation ; 30 patients ( 7 % ) developed HCC , 67 individuals in stage 1 ( 22 % ) developed varices and any event of clinical decompensation occurred in 80 patients ( 20 % ) . The 6-year cumulative overall mortality or liver transplantation was 15 % and 45 % , for stages 1 and 2 , respectively ( p<0.001 ) . The cumulative 6-year HCC incidence was significantly higher among patients with varices ( 29 % ) than those without varices ( 9 % ) , p<0.001 . Similarly , the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 ( 66 % ) as compared to 26 % in those with stage 1 , respectively ( p<0.001 ) . CONCLUSIONS Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices ( stage 2 ) PURPOSE Despite the absence of conclusive data , portal vein ( PV ) thrombosis is considered a contraindication to transarterial chemoembolization ( TACE ) in patients with unresectable hepatocellular carcinoma ( HCC ) . The purpose of our study was to establish the safety of TACE in such patients and identify key prognostic factors and survival . MATERIAL S AND METHODS Data were prospect ively collected from 32 consecutive patients with unresectable HCC and PV thrombosis who underwent treatment with TACE .  History and physical examination , relevant laboratory values , and contrast material -enhanced magnetic resonance ( MR ) images were obtained before each TACE procedure . Repeated TACE was performed every 6 weeks unless patients developed a contraindication or MR imaging showed complete response . RESULTS Median overall survival was 9.5 months ( range , 3 - 50 months ) . Child-Pugh numerical disease stage was the prognostic factor most strongly related to survival . The 30-day mortality rate was zero and there was no evidence of TACE-related hepatic infa rct ion or acute liver failure . The 6- , 9- , 12- , and 18-month survival rates were 60 % , 47 % , 25 % , and 12.5 % , respectively . CONCLUSIONS PV thrombosis should not be considered a contraindication to TACE . Compared with historical control subjects who received traditional forms of treatment , the patients in the present study had extended survival . However , prospect i ve r and omized trials are necessary to show this conclusively and to show which subgroups benefit Transcatheter arterial chemoembolization ( TACE ) has been contraindicated for the treatment of patients with hepatocellular carcinoma ( HCC ) and main portal vein ( MPV ) obstruction because of the potential risk of hepatic insufficiency result ing from ischemia after TACE . The current controlled study was undertaken to assess the safety , efficacy , and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV UNLABELLED Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression , liver decompensation , or adverse effects . While postprogression survival is clearly determined by the pattern of tumor progression , underst and ing the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design . Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included .  Postsorafenib survival ( PSS ) was calculated from the last day of treatment to death or last visit available . Two hundred and sixty patients were included in this prospect i ve study , aged 67 years , 60 % with hepatitis C , 51 % Child-Pugh A , 83 % performance status ( PS ) ≥1 , 41 % with macroscopic vascular invasion , and 38 % with extrahepatic tumor spread .  Overall , median PSS was 4.1 ( 3.3 - 4.9 ) months , result ing from 4.6 ( 3.3 - 5.7 ) months for 123 progressors , 7.3 ( 6.0 - 10.0 ) months in 77 with adverse effects , and 1.8 ( 1.6 - 2.4 ) months in 60 decompensated patients ( P < 0.001 ) 
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As the acceptability curves shown , full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries .
Conclusions Dose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients .
However , when confining the comparisons between full-dose sorafenib and TACE , full-dose sorafenib was cost-effective for these patients , under the accepted thresholds of WTP