Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions

Abstract

Chronic liver disease (CLD) and its complications constitute a significant cause of mortality and morbidity worldwide. Most deaths are secondary to the decompensation of cirrhosis and evolution of portal hypertension (PHTN). Since disease progression reversal is hardly attainable after decompensated cirrhosis develops, it is essential to intervene early with a therapeutic agent or regimen that could prevent or slow disease evolution. Thus far, there has been no agreed-upon medication to help in the fight against the development of cirrhosis or its decompensation. While early data depicted statins as harmful agents for the liver, current evidence from preclinical and clinical studies suggests that they might have positive impact on CLD. Low-quality evidence supports the fact that statins reduce mortality in CLD. Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis. Combining this data with the long track-record of safety and tolerability of statins and their potential benefits in hepatocellular carcinoma (HCC) risk reduction, hepatologists might soon rely on statins to achieve better outcomes in their CLD and cirrhotic patients without significant additional costs. This review describes the rationale behind the use of statins in patients with CLD and cirrhosis. It sheds light on the current preclinical and clinical studies that reflect beneficial effects of the use of different types and doses of statins in the treatment of patients with different types and stages of CLD and cirrhosis. It also emphasizes the need for designing and developing additional large prospective interventional randomized control trials (RCTs) to better evaluate the association between statin exposure and the risk of fibrosis progression and development of cirrhosis in patients with non-cirrhotic CLDs, the risk of progression of PHTN in patients with cirrhosis, and the mortality rates in patients with cirrhotic or non-cirrhotic CLDs.

Association between treatment‐emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study

“…However, patients receiving statins had numerically longer median OS (17.2 months) compared to patients not receiving statins (13.4 months). Even though we cannot ascertain that statins were prescribed before lenvatinib treatment, and we could not directly link statins with development of CSTE‐HTN or improved OS, previous studies have indicated survival benefits from statins in advanced liver disease 23,42,43 . In contrast, β‐blockers (that could have been administered at enrollment or during lenvatinib treatment due to treatment‐emergent HTN) showed no benefit in increasing OS.…”

“…11 In our post hoc analysis, CSTE-HTN occurred in 44.5% of patients receiving lenvatinib, a percentage comparable to the prevalence of HTN in the general population adjusted by age (45.4%), 37 the incidence of HTN associated with angiogenic agents (19%-67%), 38 and the prevalence of HTN as a cardiovascular comorbidity in cancer registries (38%). 23,42,43 In contrast, βblockers (that could have been administered at enrollment or during lenvatinib treatment due to treatment-emergent HTN) showed no benefit in increasing OS. In-depth studies are, however, needed to validate this preliminary exploratory data.…”

Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis

“…Similarly, sodium-glucose transporter inhibitors (SGLT-2i) may have a role in the treatment of MASH by reducing liver stiffness measurement, although not confirmed yet by high-quality RCTs if this is a direct liver effect or from controlling metabolic and cardiorenal disturbances [28]. Growing evidence from emerging retrospective studies and RCTs demonstrates a potential benefit of atorvastatin use in patients with chronic liver disease by improving the clinical outcomes and liver histology and enzymes, but additional large prospective RCTs are needed to be conducted to further explore the association between statin exposure and the risk of liver disease progression [29]. In the same context with other medical treatments, although metformin had demonstrated promising results in experimental studies on the reversal of cirrhosisrelated histologic changes, these findings were not confirmed in subsequent clinical trials [27].…”

Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

“…Stable cholesterol levels, despite the increased use of statins, is coherent with previous data showing increased cholesterol levels after HCV eradication [ 22 , 26 , 27 ]. The effect of statin on fibrosis levels is yet to be clarified; however, some studies showed an association of the former with decreased inflammation and fibrosis [ 52 , 53 ].…”