Addition of statins to the standard treatment in patients with cirrhosis:Safety and efficacy

This review summarizes the safety and efficacy of statins in patients with cirrhosis.Due to concerns about the safety of statins in patients with impaired liver function,they have recently been investigated as a potential treatment option in cirrhosis.The most clinically significant adverse event is statin-related myopathy,and this may be related to the high serum statin concentrations in the setting of severely impaired liver function.Rhabdomyolysis is the most serious and potentially life-threatening manifestation.It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values,such as 40 mg/d,are associated with many adverse events,especially muscle injury.Likewise,simvastatin should not be administered to patients with Model for End-stage Liver Disease score>12 and/or Child-Pugh class C because of the high risk of severe muscle injury.Due to the pleiotropic effects,the focus on statins has shifted from being considered harmful to something useful.Through these effects,statins could prevent liver-related morbidity and mortality in cirrhotic patients.Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation,hepatocellular carcinoma development and death.The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure,quite likely through a reduction in hepatic resistance.Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate.Despite these encouraging outcomes,the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved.Therefore,it is advisable to perform further randomized controlled trials on a large series of patients with hard clinical endpoints,using different statin types and varying doses.The objectives would be to prevent liver-related morbidity and mortality rather than treating cirrhosis complications to take additional information that makes it possible to add statins to the standard of care of these patients.

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.