Long-term clinical outcomes and management of hypertriglyceridemia in children with Apo-CII deficiency.

BACKGROUND AND AIM: APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. METHODS AND RESULTS: The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277-14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). CONCLUSIONS: Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). METHODS: This was a nationwide observational cohort study conducted from August 2017 until June 2021. RESULTS: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P < .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P < .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P < .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. CONCLUSION: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.

Cholestatic Pruritus Treatments in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: A Systematic Literature Review.

BACKGROUND AND AIMS: We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS: Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs. RESULTS: Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes. CONCLUSIONS: There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.

Statin, Ezetimibe, or Fibrate Initiation and Subsequent Use for the Primary and Secondary Prevention of Cardiovascular Diseases among Japanese Patients Aged ≥55 Years: A Nationwide Cohort Study.

The use of lipid-modifying agents (LMAs) other than statins has rarely been reported in real clinical settings. We aimed to compare the initiation and subsequent use of LMA classes for prevention of cardiovascular diseases. Using the national claims database, this retrospective cohort study was conducted on patients aged ≥55 years who initiated to use statins, ezetimibe, or fibrates between Fiscal Years (FYs) 2014 and 2017 as the first pharmacotherapy for dyslipidemia in Japan. A permissible gap for defining persistence was set as the median days of supply of a class to an individual. Kaplan-Meier estimates were calculated for rates. Cohorts for primary prevention without/with risk and secondary prevention comprised 1307438, 908378, and 503059 initiators for statins; 44116, 34206, and 11373 for ezetimibe; and 124511, 96380, and 27751 for fibrates. The persistence rates declined shortly after the therapy initiation regardless of the classes, which was approximately 50% at 1 year for any class for primary prevention without risk. A notable sex difference in terms of persistence rates was observed only for statins of secondary prevention. The restarting rates were similar between prevention settings: approximately 50-60% for statins and 30-40% for ezetimibe and fibrates 1 year after first discontinuation. For ezetimibe and fibrates, approximately 10% of initiators were added or switched to statins within 1 year of initiation. Collectively, any class tended to be discontinued early and some restarted; however, there were some unique classes. The findings are useful for improvement of dyslipidemia therapy.

Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.

OBJECTIVE: Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. MATERIALS AND METHODS: In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. RESULTS: Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p < 0.001, respectively). Plasma glucose tended to increase (p = 0.070) and hemoglobin A1c significantly increased (p < 0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. CONCLUSION: Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.

Fibrates, Hypertriglyceridemia, and CVD Risk: Where Do We Stand After the PROMINENT Trial for Triglyceride Lowering?

PURPOSE OF REVIEW: To evaluate recent clinical trials focusing on patients with hypertriglyceridemia. RECENT FINDINGS: Randomized clinical trials have recently been undertaken in hypertriglyceridemic patients to determine whether effective reductions in triglycerides would improve cardiovascular disease (CVD) outcomes. However, the fibric acid derivative, pemafibrate, failed to reduce cardiovascular events despite significant reductions (~ 25-35%) in triglyceride levels and despite background statin therapy. In contrast, icosapent ethyl, a highly purified omega-3 fatty acid was previously shown to reduce CVD events in hypertriglyceridemic patients, despite more modest reductions (~ 20%) in triglyceride levels in statin treated patients. The divergent results obtained in patients with hypertriglyceridemia (HTG), a group at particularly high risk of CVD, especially when coupled with other risk factors, indicates that triglyceride lowering in of itself is insufficient to offset CVD risk. Rather, the effectiveness of therapy in this high-risk cohort may be the result of the suppression of the inherent atherogenic properties associated with HTG.

Confirmation of Statin and Fibrate Use from Small-Volume Archived Plasma Samples by High-Throughput LC-MS/MS Method.

Designing studies for lipid-metabolism-related biomarker discovery is challenging because of the high prevalence of various statin and fibrate usage for lipid-lowering therapies. When the statin and fibrate use is determined based on self-reports, patient adherence to the prescribed statin dose regimen remains unknown. A potentially more accurate way to verify a patient's medication adherence is by direct analytical measurements. Current analytical methods are prohibitive because of the limited panel of drugs per test and large sample volume requirement that is not available from archived samples. A 4-min-long method was developed for the detection of seven statins and three fibrates using 10 µL of plasma analyzed via reverse-phase liquid chromatography and tandem mass spectrometry. The method was applied to the analysis of 941 archived plasma samples collected from patients before cardiac catheterization. When statin use was self-reported, statins were detected in 78.6% of the samples. In the case of self-reported atorvastatin use, the agreement with detection was 90.2%. However, when no statin use was reported, 42.4% of the samples had detectable levels of statins, with a similar range of concentrations as the samples from the self-reported statin users. The method is highly applicable in population studies designed for biomarker discovery or diet and lifestyle intervention studies, where the accuracy of statin or fibrate use may strongly affect the statistical evaluation of the biomarker data.

Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies.

The metabolically active retina obtains essential lipids by endogenous biosynthesis and from the systemic circulation. Clinical studies provide limited and sometimes conflicting evidence as to the relationships between circulating lipid levels and the development and progression of diabetic retinopathy in people with diabetes. Cardiovascular-system-focused clinical trials that also evaluated some retinal outcomes demonstrate the potential protective power of lipid-lowering therapies in diabetic retinopathy and some trials with ocular primary endpoints are in progress. Although triacylglycerol-lowering therapies with fibrates afforded some protection against diabetic retinopathy, the effect was independent of changes in traditional blood lipid classes. While systemic LDL-cholesterol lowering with statins did not afford protection against diabetic retinopathy in most clinical trials, and none of the trials focused on retinopathy as the main outcome, data from very large database studies suggest the possible effectiveness of statins. Potential challenges in these studies are discussed, including lipid-independent effects of fibrates and statins, modified lipoproteins and retinal-specific effects of lipid-lowering drugs. Dysregulation of retinal-specific cholesterol metabolism leading to retinal cholesterol accumulation and potential formation of cholesterol crystals are also addressed.

Recent Updates in Hypertriglyceridemia Management for Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: Mounting evidence continues to support the causal role of triglyceride-rich lipoproteins (TRL) in the development of atherosclerotic cardiovascular disease (ASCVD). Substantial residual ASCVD risk remains among high-risk patients who have elevated triglycerides despite reduction in low-density lipoprotein cholesterol (LDL-C) with statin therapy. Ongoing research efforts have focused on evaluating triglyceride-lowering therapies among patients with hypertriglyceridemia. RECENT FINDINGS: The REDUCE-IT trial showed that the addition of icosapent ethyl, a highly purified form of eicosapentaenoic acid (EPA), can reduce vascular events among statin-treated individuals with elevated triglycerides who have either clinical ASCVD or diabetes plus another risk factor. Although additional evidence for EPA has emerged from other trials, conflicting results have been reported by subsequent trials that tested different omega-3 fatty acid formulations. Randomized clinical trials have not demonstrated incremental ASCVD benefit of fibrates on background of statin therapy, but fibrates are used to help prevent pancreatitis in patients with severe hypertriglyceridemia. Selective inhibitors of apolipoprotein C-III (apoC3) and angiopoietin-like protein 3 (ANGPTL3), proteins that are involved in metabolism of TRLs by regulating lipoprotein lipase, have been tested in selected patient populations and showed significant reduction in triglyceride and LDL-C levels. Statin therapy continues to be the cornerstone of pharmacologic reduction of cardiovascular risk. High-dose EPA in the form of icosapent ethyl has been demonstrated to have cardiovascular benefit on top of statins in persons with elevated triglycerides at high ASCVD risk. Ongoing clinical trials are evaluating novel selective therapies such as apoC3 and ANGPTL3 inhibitors.

Triglyceride-Rich Lipoprotein Remnants and Cardiovascular Disease.

BACKGROUND: Triglycerides, cholesterol, and their metabolism are linked due to shared packaging and transport within circulating lipoprotein particles. While a case for a causal role of cholesterol-carrying low-density lipoproteins (LDLs) in atherosclerosis is well made, the body of scientific evidence for a causal role of triglyceride-rich lipoproteins (TRLs) is rapidly growing, with multiple lines of evidence (old and new) providing robust support. CONTENT: This review will discuss current perspectives and accumulated evidence that an overabundance of remnant lipoproteins stemming from intravascular remodeling of nascent TRLs-chylomicrons and very low-density lipoproteins (VLDL)-results in a proatherogenic milieu that augments cardiovascular risk. Basic mechanisms of TRL metabolism and clearance will be summarized, assay methods reviewed, and pivotal clinical studies highlighted. SUMMARY: Remnant lipoproteins are rendered highly atherogenic by their high cholesterol content, altered apolipoprotein composition, and physicochemical properties. The aggregate findings from multiple lines of evidence suggest that TRL remnants play a central role in residual cardiovascular risk.

Prevalence of and Factors Associated With the Prescription of Fibrates Among Patients Receiving Lipid-Lowering Drugs in Germany.

ABSTRACT: Little recent data are available about the patterns of prescription for fibrates in patients followed in primary care practices. Therefore, the goal of this study was to analyze the prevalence of and the factors associated with the use of fibrates among patients receiving lipid-lowering drugs in Germany. The study included patients aged ≥18 years with at least 1 visit to 1 of 1070 general practices in Germany between January and December 2019. Lipid-lowering drugs included statins (without and with ezetimibe) and fibrates. The prevalence of the prescription of fibrates corresponded to the number of patients with at least 1 prescription for fibrates divided by the total number of patients receiving lipid-lowering drugs. A logistic regression model was used to assess the relationship between several demographic, clinical, and biological factors and the prescription of fibrates. A total of 111,329 patients were included in this study (mean [SD] age 68.8 [11.5] years; 56.0% of patients were men). The prevalence of the prescription of fibrates was 1.5%. Male sex, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride were positively associated with the use of fibrates. By contrast, there was a negative relationship between the odds of receiving fibrates and coronary heart disease, myocardial infarction, peripheral arterial disease, and stroke including transient ischemic attack. Overall, we found that fibrates were infrequently prescribed in general practices in Germany.

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα): New Opportunities to Reduce Residual Cardiovascular Risk in Chronic Kidney Disease?

PURPOSE OF REVIEW: Chronic kidney disease (CKD) poses a major global challenge, which is exacerbated by aging populations and the pandemic of type 2 diabetes mellitus. Much of the escalating burden of CKD is due to cardiovascular complications. Current treatment guidelines for dyslipidemia in CKD prioritize low-density lipoprotein cholesterol management, but still leave a high residual cardiovascular risk. Targeting elevated triglycerides and low plasma high-density lipoprotein cholesterol, a common feature of CKD, could offer additional benefit. There are, however, safety issues with current fibrates (peroxisome proliferator-activated receptor alpha [PPARα] agonists), notably the propensity for elevation in serum creatinine, indicating the need for new approaches. RECENT FINDINGS: Interactions between the ligand and PPARα receptor influence the specificity and potency of receptor binding, and downstream gene and physiological effects. The peroxisome proliferator-activated receptor alpha modulator (SPPARMα) concept aims to modulate the ligand structure so as to enhance binding at the PPARα receptor, thereby improving the ligand's selectivity, potency, and safety profile. This concept has led to the development of pemafibrate, a novel SPPARMα agent. This review discusses evidence that differentiates pemafibrate from current fibrates, especially the lack of evidence for elevation in serum creatinine or worsening of renal function in high-risk patients, including those with CKD. Differentiation of pemafibrate from current fibrates aims to address unmet clinical needs in CKD. The ongoing PROMINENT study will provide critical information regarding the long-term efficacy and safety of pemafibrate in patients with type 2 diabetes mellitus, including those with CKD, and whether the favorable lipid-modifying profile translates to reduction in residual cardiovascular risk.

The Chylomicronemia Syndrome Is Most Often Multifactorial: A Narrative Review of Causes and Treatment.

The chylomicronemia syndrome occurs when triglyceride levels are severely elevated (usually >16.95 mmol/L [1500 mg/dL]) and is characterized by such clinical features as abdominal pain, acute pancreatitis, eruptive xanthomas, and lipemia retinalis. It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. Most chylomicronemia syndrome cases are the result of MFCS; FCS is very rare. In all these conditions, triglyceride-rich lipoproteins accumulate because of impaired plasma clearance. This review describes the 3 major causes of the chylomicronemia syndrome; their consequences; and the approaches to treatment, which differ considerably by group.

Triglycerides and endothelial function: molecular biology to clinical perspective.

PURPOSE OF REVIEW: Recently, a high level of triglycerides has attracted much attention as an important residual risk factor of cardiovascular events. We will review and show the mechanisms underlying the association of endothelial dysfunction with hypertriglyceridemia and present clinical evidence for a relationship between endothelial function and triglycerides. RECENT FINDINGS: Clinical studies have shown that hypertriglyceridemia is associated with endothelial dysfunction. It is likely that hypertriglyceridemia impairs endothelial function through direct and indirect mechanisms. Therefore, hypertriglyceridemia is recognized as a therapeutic target in the treatment of endothelial dysfunction. Although experimental and clinical studies have shown that fibrates and omega-3 fatty acids not only decrease triglycerides but also improve endothelial function, the effects of these therapies on cardiovascular events are controversial. SUMMARY: Accumulating evidence suggests that hypertriglyceridemia is an independent risk factor for endothelial dysfunction. Triglycerides should be considered more seriously as a future target to reduce cardiovascular events. Results of ongoing studies may show the benefit of lowering triglycerides and provide new standards of care for patients with hypertriglyceridemia possibly through improvement in endothelial function.

Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD.

PURPOSE OF REVIEW: Apolipoprotein C-III (apoC-III) is known to inhibit lipoprotein lipase (LPL) and function as an important regulator of triglyceride metabolism. In addition, apoC-III has also more recently been identified as an important risk factor for cardiovascular disease. This review summarizes the mechanisms by which apoC-III induces hypertriglyceridemia and promotes atherogenesis, as well as the findings from recent clinical trials using novel strategies for lowering apoC-III. RECENT FINDINGS: Genetic studies have identified subjects with heterozygote loss-of-function (LOF) mutations in APOC3, the gene coding for apoC-III. Clinical characterization of these individuals shows that the LOF variants associate with a low-risk lipoprotein profile, in particular reduced plasma triglycerides. Recent results also show that complete deficiency of apoC-III is not a lethal mutation and is associated with very rapid lipolysis of plasma triglyceride-rich lipoproteins (TRL). Ongoing trials based on emerging gene-silencing technologies show that intervention markedly lowers apoC-III levels and, consequently, plasma triglyceride. Unexpectedly, the evidence points to apoC-III not only inhibiting LPL activity but also suppressing removal of TRLs by LPL-independent pathways. Available data clearly show that apoC-III is an important cardiovascular risk factor and that lifelong deficiency of apoC-III is cardioprotective. Novel therapies have been developed, and results from recent clinical trials indicate that effective reduction of plasma triglycerides by inhibition of apoC-III might be a promising strategy in management of severe hypertriglyceridemia and, more generally, a novel approach to CHD prevention in those with elevated plasma triglyceride.

Treatment with fibrates is associated with higher LAL activity in dyslipidemic patients.

Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters (CE) and triglycerides (TG) within the lysosomes; generated cholesterol and free fatty acids (FFA) are released in the cytosol where they can regulate their own synthesis and metabolism. When LAL is not active, as in case of genetic mutations, CE and TG accumulate in the lysosomal compartment, while the lack of release of cholesterol and FFA in the cytosol leads to an upregulation of their synthesis. Thus, LAL plays a central role in the intracellular homeostasis of lipids. Since there are no indications about the effect of different lipid-lowering agents on LAL activity, aim of the study was to address the relationship between LAL activity and the type of lipid-lowering therapy in a cohort of dyslipidemic patients. LAL activity was measured on dried blood spot from 120 patients with hypercholesterolemia or mixed dyslipidemia and was negatively correlated to LDL-cholesterol levels. Among enrolled patients, ninety-one were taking one or more lipid-lowering drugs, as statins, fibrates, ezetimibe and omega-3 polyunsaturated fatty acids. When patients were stratified according to the type of lipid-lowering treatment, i.e. untreated, taking statins or taking fibrates, LAL activity was significantly higher in those with fibrates, even after adjustment for sex, age, BMI, lipid parameters, liver function, metabolic syndrome, diabetes and statin use. In a subset of patients tested after 3 months of treatment with micronized fenofibrate, LAL activity raised by 21%; the increase was negatively correlated with baseline LAL activity. Thus, the use of fibrates is independently associated with higher LAL activity in dyslipidemic patients, suggesting that the positive effects of PPAR-α activation on cellular and systemic lipid homeostasis can also include an improved LAL activity.

Curbing Lipids: Impacts ON Cancer and Viral Infection.

Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include signaling, storing energy, and acting as the central structural component of cell membranes. Alteration of lipid metabolism is a prominent feature of cancer, as cancer cells must modify their metabolism to fulfill the demands of their accelerated proliferation rate. This aberrant lipid metabolism can affect cellular processes such as cell growth, survival, and migration. Besides the gene mutations, environmental factors, and inheritance, several infectious pathogens are also linked with human cancers worldwide. Tumor viruses are top on the list of infectious pathogens to cause human cancers. These viruses insert their own DNA (or RNA) into that of the host cell and affect host cellular processes such as cell growth, survival, and migration. Several of these cancer-causing viruses are reported to be reprogramming host cell lipid metabolism. The reliance of cancer cells and viruses on lipid metabolism suggests enzymes that can be used as therapeutic targets to exploit the addiction of infected diseased cells on lipids and abrogate tumor growth. This review focuses on normal lipid metabolism, lipid metabolic pathways and their reprogramming in human cancers and viral infection linked cancers and the potential anticancer drugs that target specific lipid metabolic enzymes. Here, we discuss statins and fibrates as drugs to intervene in disordered lipid pathways in cancer cells. Further insight into the dysregulated pathways in lipid metabolism can help create more effective anticancer therapies.

Risk stratification and treatment of primary biliary cholangitis.

Primary biliary cholangitis is a chronic liver disorder characterized by progressive cholestasis that may evolve to liver cirrhosis. While ursodeoxycholic acid is the treatment of choice, around 30% of patients do not respond to this therapy. These patients have a poorer prognosis, hence should be identified early in order to be offered therapy options. Along these lines, improved understanding of the condition's pathophysiology has allowed the development of newer drugs, including obeticholic acid and fibrates. This review offers a perspective on risk stratification and treatment for these patients, from ursodeoxycholic acid to second-line treatments.