You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial
Abstract 1:
Background Chronic hepatitis B ( CHB ) can progress to cirrhosis , hepatocellular carcinoma ( HCC ) and ultimately liver-related death . Although oral antiviral therapy for patients with CHB reduces the risk of such complications , once cirrhosis is established , the benefits of antiviral therapy are not robustly demonstrated . According to traditional Chinese medicine ( TCM ) , some Chinese herbal medicines promote blood circulation and soften hard masses , and therefore they may block and reverse hepatic fibrosis . The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan ( RGT ) administered for fibrosis , and entecavir ( ETV ) , on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis . Methods / design This multicenter , central ly r and omized , double-blind , placebo-controlled , parallel-group study is planned to complete within 5 years . For the study , 1,000 with CHB or HBV-related compensated cirrhosis are r and omly assigned in a 1:1 ratio to a treatment group ( 0.5 mg ETV once daily ; 2 g RGT three times daily ) or a control group ( 0.5 mg ETV once daily ; 2 g RGT dummy agent three times daily ) . The primary end points are the development of HCC and liver-related death . Secondary end points include disease progression and overall survival . Discussion Although antiviral therapy can achieve sustained suppression of HBV replication , thereby preventing cirrhosis , patients with CHB treated with nucleos(t)ide analogs ( NUCs ) retain a higher risk for HCC compared with patients with inactive disease . Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis , the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear . Therefore , it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large , prospect i ve , multicenter , double-blind , r and omized , controlled trials in China . Trial registration Clinical Trials.gov Identifier : NCT01965418 . Date registered : 17 October


Title 2:
Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study
Abstract 2:
Objective To evaluate the risk and predictors of hepatocellular carcinoma ( HCC ) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy . Design Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective– prospect i ve cohort who were treated with nucleos(t)ide analogue(s ) starting with lamivudine monotherapy for ≥12 months . Setting A nationwide network of liver centres . Patients 818 patients were included : 517 with chronic hepatitis B only ; 160 with compensated cirrhosis ; 56 with decompensated cirrhosis ; 85 with unclassified disease severity . Interventions All patients were treated with nucleos(t)ide analogue(s ) starting with lamivudine monotherapy . Main outcome measures Development of HCC . Results During a median follow-up of 4.7 years , HCC developed in 49 ( 6.0 % ) patients . The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only ( 11.5 % vs 3.2 % , respectively ; p<0.001 ) . HCC developed in 0.7 % , 6.7 % and 11.7 % of patients < 50 , 50–60 and > 60 years old , respectively ( p<0.001 ) . Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis , but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only ( p=0.076 ) . In multivariate analysis , age , gender and cirrhosis were independently associated with HCC risk regardless of virological remission . Conclusions Long-term therapy with nucleos(t)ide analogue(s ) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis , who should remain under HCC surveillance even during effective therapy . Older age and male gender remain independent risk factors for HCC , while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC


Title 3:
[Clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus-related cirrhosis].
Abstract 3:
OBJECTIVE To investigate the clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus (HBV)-related cirrhosis . METHODS A total of 163 patients with HBV-related cirrhosis were recruited for treatment between March 2010 and August 2012 , and divided into the following three groups : group A ( n = 56 ) received Fufang Biejia Ruangan Tablet plus entecavir ; group B ( n = 52 ) received entecavir only ; and group C ( n = 55 ) received Fufang Biejia Ruangan tablet only . Enzyme-linked immunoassay methods were used to measure serum levels of hyaluronic acid ( HA ) , laminin ( LN ) , collagen ( PCIV ) and prolyl endopeptidase ( PLD ) . The grade of liver fibrosis was determined upon liver biopsy , and score of liver stiffness was measured by FibroScan . RESULTS All three treatment groups showed significant decreases from baseline in serum levels of alanine aminotransferase , aspartate aminotransferase , HBV DNA , HA , LN , PCIV and PLD ( all P < 0.05 ) . However , the changes in HA , LN , PCIV and PLD levels were significantly greater in group A than in either group B or C ( P < 0.05 ) . All three treatment groups showed significant improvements from baseline in liver fibrosis grade and liver stiffness score ( P < 0.05 ) . The total effective rate of group A was 82.14 % , which was significantly higher than that of groups B and C ( P < 0.05 ) . CONCLUSION Combination therapy of Fufang Biejia Ruangan tablet plus entecavir is effective for treating HBV-related cirrhosis
Results : This systematic review will provide a synthesis of RGT for hepatic fibrosis in patients with CHB from various evaluation aspects including biochemical and virological parameters , HBV DNA levels HBeAg status and seroconversion , adverse events incidence .
Conclusion : The systematic review will provide evidence to assess the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB .