***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 / Aims Angiotensin receptor blockers ( ARBs ) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance . This study compared the effects of combined treatment using the ARB c and esartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospect i ve , r and omized controlled trial . Methods Between January 2008 and July 2009 , 53 cirrhotic patients with clinical ly significant portal hypertension were r and omized to receive either c and esartan and propranolol combination therapy ( 26 patients ) or propranolol monotherapy ( 27 patients ) . Before and 3 months after the administration of the planned medication , the hepatic venous pressure gradient ( HVPG ) was assessed in both groups . The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached , and the c and esartan dose was fixed at 8 mg qd . The primary endpoint was the HVPG response rate ; patients with an HVPG reduction of > 20 % of the baseline value or to < 12 mmHg were defined as responders . Results The mean portal pressure declined significantly in both groups , from 16 mmHg ( range , 12 - 28 mmHg ) to 13.5 mmHg ( range , 6 - 20 mmHg ) in the combination group ( P<0.05 ) , and from 17 mmHg ( range , 12 - 27 mmHg ) to 14 mmHg ( range , 7 - 25 mmHg ) in the propranolol monotherapy group ( P<0.05 ) . However , the medication-induced pressure reduction did not differ significantly between the two groups [ 3.5 mmHg ( range , -3 - 11 mmHg ) vs. 3 mmHg ( range , -8 - 10 mmHg ) , P=0.674 ] . The response rate ( 55.6 % vs. 61.5 % , P=0.435 ) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups . Conclusions The addition of c and esartan ( an ARB ) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension , and is thus not recommended Background Therapies that can slow the progression of liver fibrosis in chronic liver disease are needed . Evidence suggests that the renin-angiotensin system ( RAS ) contributes to inflammation and fibrosis in chronic liver disease . Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors ( ACEi ) and angiotensin receptor-1 [ AT-1 ] blockers ( ARBs ) has antifibrogenic properties . Aims In this study , we evaluated the effects of continuous ACEi/ARB use for 3.5 years on histological liver fibrosis progression in the HALT-C Trial cohort . Methods In the HALT-C Trial , subjects with chronic hepatitis C and advanced hepatic fibrosis ( Ishak stage ≥3 ) underwent serial liver biopsies at baseline , 1.5 years , and 3.5 years after r and omization . The primary outcome was a ≥2-point increase in Ishak fibrosis score in at least one of the two serial biopsies . Sixty-six subjects were continuously taking ACEi/ARBs over the observation period , 126 were taking other antihypertensive medications , and 343 subjects took no antihypertensive medications . Results The three groups were similar in baseline fibrosis scores , and the two groups being treated with antihypertensives were taking a similar number of antihypertensive medications . Fibrosis progression occurred in 33.3 % of the ACEi/ARB group , 32.5 % of the other antihypertensive medications group , and in 25.7 % of subjects taking no antihypertensive medications . No significant associations between ≥2-point increases in fibrosis scores and continuous ACEi/ARB use were apparent at either 1.5 or 3.5 years in diabetes-adjusted and unadjusted odds ratios . Conclusions ACEi/ARB therapy did not retard the progression of hepatic fibrosis BACKGROUND Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo . However , no study was done in humans with alcoholic liver disease . AIM To investigate the antifibrotic effect of angiotensin II type 1 receptor ( AT1-R ) blocking agents ( ARB ) in patients with alcoholic liver disease . METHODS The primary outcome was improvement in patients ' histological features . Eighty-five patients with compensated alcoholic liver fibrosis ( ≥ F2 ) which was confirmed by baseline liver biopsy were r and omized ( intention-to-treat ( ITT ) ) to receive either ARB , c and esartan ( 8 mg/day ) with ursodeoxycholic acid ( UDCA ) ( 600 mg/day ) ( n = 42 ) or UDCA alone ( n = 43 ) as control for 6 months and follow-up liver biopsies were conducted . RESULTS According to the Laennec fibrosis system , c and esartan showed significantly higher rates of histological improvements ( ITT , 33.3 % vs. 11.6 % , P = 0.020 ) . In addition , the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 ( P = 0.005 ) in the c and esartan group . C and esartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 ( % ) , and the hydroxyproline levels ( μg/g liver tissue ) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively ( P < 0.05 ) . In addition , the relative expression of transforming growth factor-β1(TGF-β1 ) , collagen-1 , AT1-R , tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) , metalloproteinases2 ( MMP2 ) , Rac1 and p22phox by real-time RT-PCR decreased in the c and esartan group ( P < 0.05 ) . Mean arterial blood pressure in the c and esartan group decreased mildly but significantly ( P < 0.001 ) . No significant complications and side effects were observed during the present study . CONCLUSIONS Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements 
    Output:
    
Serum fibrosis markers such as TGF-β1 , collagen I , IV , TIMP-1 , and MMP2 were significantly reduced in the intervention group .
No significant difference was found in serum creatinine levels between the intervention and control groups , and significant renal dysfunction was not observed after administration of RAS inhibitors .
Conclusions RAS inhibitors are potential therapeutic agents for hepatic fibrosis , which can be safely used in patients with chronic liver disease