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For nearly 30 years ursodeoxycholic acid (UDCA) represented the only pharmacological treatment option available for primary biliary cholangitis (PBC). This changed at the end of 2016 when obeticholic acid was licensed in Europe for PBC patients not responding to UDCA. Novel treatment concepts involving the modulation of nuclear receptor signaling in cholestatic and other liver diseases have led to a host of new potential options, studies and drug candidates for the treatment of PBC. The analysis of large multinational cohorts has additionally confirmed the effectiveness of UDCA in slowing PBC progression, and has led to the development of new definitions for the risk assessment of PBC patients under therapy, which will be an asset for clinical decision making. One issue that remains unresolved is the therapeutic management of extrahepatic symptoms associated with PBC, namely fatigue and pruritus, which are the main factors influencing the quality of life of affected individuals. Their pathophysiological basis is poorly understood and treatment remains unsatisfactory.

A 42-year-old man with long-standing HIV-infection (CDC C3) and multiple treatment failures was seen for follow-up 6 months after starting a new HAART (zidovudine, efavirenz, indinavir, ritonavir). The medical history is remarkable for a hypersensitivity reaction to abacavir, past smoking (10 pack years) and a family history of coronary heart disease of the patient's mother. Physical examination revealed discrete signs of lipoatrophy of the face, arms and legs, but no lipoaccumulation (hip-waist ratio 0.94; body mass index 22 kg/m2). Blood pressure measured 156/92 mmHg.A rise in CD4 cell count from 24/ microL to 60/ microL was noted. For the first time, the HIV viral load decreased to50 copies/mL. Concentrations of triglycerides and cholesterol were found to be increased to 26 mmol/L (2275 mg/dL) and 15 mmol/L (580 mg/dL), respectively, compared previously normal readings. Other parameters were in the normal range.Continuation of HAART resulted in rising CD4 counts to200/ microL and HIV viral load suppression to50 copies/mL. Neither dietary measures nor treatment with pravastatin significantly changed the drug-induced mixed hyperlipidemia. Treatment with fenofibrate (200 mg qd), however, was followed by a significant reduction of triglyceride and cholesterol concentrations to 12 mmol/L (1050 mg/dL) and 10 mmol/L (387 mg/dL). Addition of pravastatin did not result in further improvement. Arterial hypertension was diagnosed by ambulatory 24-h blood pressure monitoring (systolic 157+/-11 mmHg; diastolic 97+/-10 mmHg).HAART-induced mixed hyperlipidaemia is likely to increase the cardiovascular risk. According to first estimates, the 3-year risk of myocardial infarction amounts to 1.29 - 2.09 % for our patient. The 3-year risk of HIV progression to AIDS or death is30 % if HAART is stopped or fails upon switching due to unknown archived drug resistance. Thus, despite unsatisfactory lipid profiles, a modification of HAART seems only acceptable, if new, equally potent, but less lipidaemic drug combinations are available.

Peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha, PPAR gamma) are nuclear transcription factors regulating gene expression in response to their ligands. Initially, PPARs were identified as regulators of gene expression in lipid metabolism and adipogenesis, but recent work has demonstrated PPAR expression in vascular cells and suggests antiinflammatory properties in the vasculature. Since PPAR alpha activators include lipid-lowering fibric acid derivatives and since PPAR gamma can be activated by antidiabetic thiazolidinediones, activation of these receptors might be an intriguing tool to influence atherogenesis in patients with vascular disease. However, there is also evidence that PPAR activators might furnish lesion development under certain circumstances. The following review will focus on these aspects of potential anti- or proatherogenic effects in the vessel wall and discuss potential clinical implications of these findings.

A 73 year old male who had been prescribed fenofibrate for years developed a slightly asymmetric paraparesis of both lower extremities. CPK values rose to 9800 U/l, EMG of the quadriceps femoris muscle was myopathic. Muscle biopsy revealed a necrotic myopathy. Discontinuation of fenofibrate induced a rapid decline of CPK values, followed by a slower remission of muscular symptoms and persisting pseudo-myotonic discharges in EMG. The spectrum of neuromuscular side effects of cholesterol lowering agents, consisting of myalgia, cramps and reversible CPK elevation, is discussed. Only rarely necrotic myopathies have been described.

In order to examine the effect of fenofibrate on coronary narrowings, within the framework of a prospective intervention study, we treated a total of 44 hypercholesterolemic patients (who were in our clinic to undergo PTCA) with diet and fenofibrate (200-400 mg/day) over a period of 3 years. After a mean interval of 21 months, control angiographies were performed in nearly identical projections for 21 patients on clinical grounds. The minor and medium-grade narrowings of the reangiographed patients at the beginning and at the end of the intervention interval were measured by means of digital image processing and automatic contour detection. The measuring parameters were percent diameter reduction (% DR) and percent plaque area (%PA). With regard to their angiographic progression, the 21 reangiographed patients of the intervention group were compared to a comparison group consisting likewise of 21 patients of similar age and sex distribution and persistently high lipid and lipoprotein levels. During the intervention period, the reangiographed patients of the intervention group showed the following changes of the lipid and lipoprotein levels in contrast to the outset values: cholesterol -19 +/- 8%, LDL -20 +/- 14%, HDL +19 +/- 44%, triglycerides -30 +/- 31%.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied a 60-year-old male with idiopathic (primary) hemochromatosis and type III hyperlipoproteinemia. Periodical phlebotomy therapy could favourably influence the disease of iron metabolism as well as the familial lipoprotein disorder in addition to fenofibrate treatment. Idiopathic hemochromatosis as aggravating cause of type III hyperlipoproteinemia has not been reported yet.

The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.