Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier?

The pandemics of coronavirus disease 2019(COVID-19)and non-alcoholic fatty liver disease(NAFLD)coexist.Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD,while preexisting liver damage from NAFLD may influence the course of COVID-19.However,the prognostic relevance of this interaction,though,is unclear.Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19.Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity.Striking molecular similarities of cytokine pathways in both diseases,including postacute sequelae of COVID-19,suggest common pathways for chronic low-activity inflammation.This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.

Molecular changes in hepatic metabolism and transport incirrhosis and their functional importance

Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.

Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: Influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC

AIM: To investigate the systemic availability of budesonide in a patient with Child A drrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma, who developed serious side effects.METHODS: Serum levels of budesonide, 6β-OH-budesonide and 16α-OH-prednisolon were measured by HPLC/MS/MS;portosysternic shunt-index (SI) was determined by 99mTc nuclear imaging. All values were compared with a matched control patient without side effects.RESULTS: Serum levels of budesonide were 13-fold increased in the index patient. The ratio between serum levels of the metabolites 6β-OH-budesonide and 16α-OH-prednisolone, respectively, and serum levels of budesonide was diminished (1.0 vs. 4.0 for 6β-OH-budesonide, 4.2 vs.10.7 for 16α-OH-prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the range of healthy subjects.CONCLUSION: Serum levels of budesonide vary up to 13-fold in AIH patients with Child A cirrhosis in the absence of relevant portosysternic shunting. Reduced hepatic metabolism, as indicated by reduced metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic side effects of this drug in cirrhosis.

Origin of and therapeutic approach to cardiac syndrome X:Results of the proton pump inhibitor therapy for angina-like lingering pain trial (PITFALL trial)

AIM: To investigate the frequency of gastroen-terological diseases in the etiology and the efficacy of proton pump inhibitors (PPIs) in the treatment of cardiac syndrome X (CSX) as a subform of non-cardiac chest pain (NCCP). METHODS: We investigated 114 patients with CSX using symptom questionnaires. A subgroup of these patients were investigated regarding upper gastrointestinal disorders (GIs) and treated with PPI. Patients not willing to participate in investigation and treatment served as control group. RESULTS: Thirty-six patients denied any residual symptoms and were not further evaluated. After informed consent in 27 of the remaining 78 patients, we determined the prevalence of disorders of the upper GI tract and quantifi ed the effect of treatment with pantoprazole. We found a high prevalence of gastroenterological pathologies (26/27 patients, 97%)with gastritis, gastroesophageal reflux disease (GERD) and acid reflux as the most common associated disorders. If treated according to the study protocol, these patients showed a significant improvement in the symptom score. Patients treated by primary care physicians, not according to the study protocol had a minor response to treatment (n = 19, -43%), while patients not treated at all (n = 26) had no improvement of symptoms (-0%). CONCLUSION: Disorders of the upper GI tract are a frequent origin of CSX in a German population and can be treated with pantoprazole if given for a longer period.

Occult celiac disease prevents penetrance of hemochromatosis

AIM: To report a patient with C282Y homozygocity, depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon glutenfree diet.METHODS: To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking, we determined the expression of divalent-metal transporter 1 (DMT1), ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohistochemistry and real-time PCR in duodenal biopsies of this patient.RESULTS: Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein and mRNA expression of DMT1 as acompensatory mechanism in this patient with HH and CD.CONCLUSION: Occult CD may compensate tot increased DMT1 expression in a specific subset of individuals withhomozygous C282Y mutations in the hemochromatosis(HFE) gene, thus contributing to the low penetrance of HH.

Screening for nonalcoholic fatty liver disease-when,who and how?

Nonalcoholic fatty liver disease(NAFLD)is becoming a frequent liver disease,especially in patients with metabolic syndrome and especially in Western countries.Complications of NAFLD comprise progressive fibrosis,cirrhosis and hepatocellular carcinoma.NAFLD also represents an independent risk factor for cardiovascular disease,extrahepatic neoplasia and other organ damage,such as renal insufficiency.Given the epidemiological importance of the disease,new developments in specific treatment of the disease and the wide availability of noninvasive techniques in estimating steatosis and fibrosis,NAFLD should be subject to screening programs,at least in countries with a high prevalence of the disease.The review discusses prerequisites for screening,cost-effectiveness,current guideline recommendations,suitability of techniques for screening and propositions for the following questions:Who should be screened?Who should perform screening?How should screening be performed?It is time for a screening program in patients at risk for NAFLD.