The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis

Purpose of review

Statins are drugs developed to treat hypercholesterolemia. Its use in patients with liver disease has been limited because one of its potential and most feared side effects is hepatotoxicity. However, there is robust evidence that supports the safety of statins in this population in the absence of severe liver dysfunction. In this review, we will summarize the efficacy and safety of statins in cirrhosis.

Recent findings

Statins are effective in the treatment of dyslipidemia in patients with liver disease, because of their pleiotropic properties. These properties are independent of their effect on cholesterol levels, such as improving endothelial dysfunction or having antioxidant, antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic, or immunomodulation properties. Statins have been studied in other areas such as in treatment of portal hypertension, prevention of hepatocellular carcinoma, and/or protection against ischemia/reperfusion injury.

Summary

Approved indications for statins in patients with cirrhosis are those of the general population, including dyslipidemia and increased cardiovascular risk. Compensated cirrhosis is not a contraindication. In patients with decompensated cirrhosis, statins should be prescribed with extreme caution at low doses, and with frequent monitoring of creatinine phosphokinase levels in order to detect adverse events in a timely fashion.

     

Consequences of treatment withdrawal in type 1 autoimmune hepatitis.

BACKGROUND AND AIMS: Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined. METHODS: The outcomes of 132 patients with definite type 1 autoimmune hepatitis who had been treated comparably until remission were assessed retrospectively after drug withdrawal. RESULTS: Patients who had relapsed repeatedly after initial treatment withdrawal developed cirrhosis more commonly than patients who sustained remission (18/48 vs 1/22, P=0.004), and those who relapsed once (18/48 vs 2/21, P=0.02). Hepatic death or the need for liver transplantation was also more frequent in the patients who had multiple relapses than those who sustained remission (13/64 vs 0/30, P=0.008) and those who relapsed once (13/64 vs 1/38, P=0.02). Patients who sustained their remission had a higher frequency of normal laboratory indices at drug withdrawal than patients who relapsed (88% vs 46%, P=0.003). Adverse outcomes after relapse did not distinguish patients until after 5 years of observation. CONCLUSIONS: Multiple relapses are associated with a poorer prognosis than sustained remission or single relapse episodes. Initial treatment to resolution of laboratory abnormalities may afford the greatest opportunity to prevent relapse.     

Clinical relevance of sarcopenia in patients with cirrhosis

The most commonly recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, susceptibility for infections, kidney dysfunction, and hepatocellular carcinoma; however, severe muscle wasting or sarcopenia are the most common and frequently unseen complications which negatively impact survival, quality of life, and response to stressor, such as infections and surgeries. At present, D’Amico stage classification, Child-Pugh, and MELD scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of assessing the nutritional and functional status. Currently, numerous methods are available to evaluate the nutrition status of the cirrhotic patient; nevertheless, most of these techniques have limitations primarily because lack of objectivity, reproducibility, and prognosis discrimination. In this regard, an objective and reproducible technique, such as muscle mass quantification with cross-sectional imaging studies (computed tomography scan or magnetic resonance imaging) constitute an attractive index of nutritional status in cirrhosis. Sarcopenia is part of the frailty complex present in cirrhotic patients, resulting from cumulative declines across multiple physiologic systems and characterized by impaired functional capacity, decreased reserve, resistance to stressors, and predisposition to poor outcomes. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis. Also, we analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in patients with cirrhosis and their impact after liver transplantation. Finally, we discuss existing and potential novel therapeutic approaches for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in an effort to reduced morbidity related and improved survival in cirrhosis.     

Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis

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Oral challenge with a methionine load in patients with inflammatory bowel disease: a better test to identify hyperhomocysteinemia

BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombosis. Hyperhomocysteinemia is one of the factors that have been related to thromboembolic complications. Patients with hyperhomocysteinemia and normal fasting homocysteine levels can be identified with an oral methionine load. We studied homocysteine levels in patients with IBD during fasting and after methionine load to determine the true prevalence of hyperhomocysteinemia and its relation with thrombotic events. METHODS: Prospective analysis of homocysteine levels in consecutive patients with IBD during fasting and 6-8 hours after an oral methionine load. Levels of folate and vitamin B12 were also determined. History of thrombotic events were recorded. RESULTS: Eighty-two patients with IBD, 56 with UC and 26 with CD were included. Eighteen patients (22%) had hyperhomocysteinemia during fasting. Mean levels of homocysteine after methionine load were 20.4 +/- 18.1 micromol/l (range, 1-79.7 micromol/l), and 43 patients (52%) had hyperhomocysteinemia (> or =20 micromol/l) after methionine load. Six patients (7.3%) had history of thrombosis. The homocysteine levels during fasting and after methionine load were significantly higher in patients with thrombotic events than in patients without thrombosis (15.5 +/- 3.7 micromol/l vs. 6.6 +/- 6.5 micromol/l; P = 0.002; 44.5 +/- 20.9 micromol/l vs. 18.4 +/- 16.5 micromol/l; P < 0.001, respectively). CONCLUSIONS: There is a higher prevalence of hyperhomocysteinemia in IBD patients than previously thought, this can be identified with an oral challenge of a methionine load. Hyperhomocysteinemia increases the risk of thromboembolic complications in patients with IBD.