Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome(MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance(IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease

AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3

Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral therapy.The pathogenetic link between IR and chronic HCV infection is complex,and is associated with HCV genotype.Liver steatosis is the most common in the patients infected with genotype 3 virus,possibly due to direct effects of genotype 3 viral proteins.To the contrary,hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism,involving IR.In HCV genotype 3,liver steatosis correlates with viral load,reverts after reaching the sustained virologic response and reoccurs in the relapsers.A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

Alimentary regimen in non-alcoholic fatty liver disease:Mediterranean diet

Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide.The mechanisms of the underlying disease development and progression are awaiting clarification.Insulin resistance and obesity-related inflammation status,among other possible genetic,dietary,and lifestyle factors,are thought to play the key role.There is no consensus concerning the pharmacological treatment.However,the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy.On the basis of its components,the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases,including obesity and diabetes.New evidence supports the idea that the Mediterranean diet,associated with physical activity and cognitive behaviour therapy,may have an important role in the prevention and the treatment of NAFLD.

Role of endoscopy in management of gastrointestinal complications of portal hypertension

The management of patients with gastrointestinal complications of portal hypertension is often complex and challenging. The endoscopy plays an important role in the management of these patients. The role of endoscopy is both diagnostic and interventional and in the last years the techniques have undergone a rapid expansion with the advent of different and novel endoscopic modalities, with consequent improvement of investigation and treatment of these patients. The choice of best therapeutic strategy depends on many factors: baseline disease, patient's clinical performance and the timing when it is done if in emergency or a prophylactic approaches. In this review we evaluate the endoscopic management of patients with the gastrointestinal complications of portal hypertension.

Silymarin: An option to treat non-alcoholic fatty liver disease

We have read with a great interest the review published by Singh et al, on the treatment options in alcoholic and non-alcoholic fatty liver disease, including various new targeted therapies that are currently under investigation. Recently, we described the health effects of the Mediterranean diet associated to an antioxidant complex rich in silymarin, to improve in overweight patients anthropometric parameters, glucose and lipid metabolism and intra-hepatic fat accumulation.

Adiponectin serum level in chronic hepatitis C infection and therapeutic profile

Hepatic steatosis is commonly seen in the patients with chronic hepatitis C virus(HCV) infection. HCV is closely associated with lipid metabolism,and viral steatosis is more common in genotype 3 infection owing to a direct cytopathic effect of HCV core protein. In non-genotype3 infection,hepatic steatosis is considered largely to be the result of the alterations in host metabolism; metabolic steatosis is primarily linked with HCV genotype 1. A d i p o s e t i s s u e s e c r e t e s d i f f e r e n t h o r m o n e s involved in glucose and lipid metabolisms. It has been demonstrated that adipocytokines are involved in the pathogenesis of non-alcoholic fatty liver disease,as the decreased plasma adiponectin levels,a soluble matrix protein expressed by adipoctyes and hepatocyte,are associated with liver steatosis. Various studies have shown that steatosis is strongly correlated negatively with adiponectin in the patients with HCV infection. The role of adiponectin in hepatitis C virus induced steatosis is still not completely understood,but the relationship between adiponectin low levels and liver steatosis is probably due to the ability of adiponectin to protect hepatocytes from triglyceride accumulation by increasing β-oxidation of free fatty acid and thus decreasing de novo free fatty acid production.

No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease

AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gluten-free diet(GFD) and harbouring persistent negative CD-related serology were recruited.Conventional risk factors for osteoporosis(e.g.,age,sex,menopausal status,history of fractures,smoke,and body mass index) were checked and BMD was assessed by dual energy X ray absorptiometry.Serum calcium and parathyroid hormone(PTH) levels were evaluated.Thirty-eight patients underwent repeat duodenal biopsy.Serum samples from a selected sub-group of 30 patients,who were also typed for human leukocyte antigen(HLA) DQ2 and DQ8 haplotype,were incubatedwith homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after immunoprecipitation.RESULTS:Despite persistent negative CD-related serology and strict adherence to GFD,49 out of the 70(74%) patients displayed low BMD.Among these patients,13(24%) showed osteoporosis and 36(76%) osteopenia.With the exception of age,conventional risk factors for osteoporosis did not differ between patients with normal and low BMD.Circulating serum calcium and PTH levels were normal in all patients.Duodenal mucosa healing was found in 31(82%) out of 38 patients who underwent repeat duodenal biopsy with 20(64%) still displaying low BMD.The remaining 7 patients had an incomplete normalization of duodenal mucosa with 6(84%) showing low BMD.No evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for,independent of BMD,duodenal histology,and HLA status.CONCLUSION:If any,the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.

Non-alcoholic fatty liver disease and beneficial effects of dietary supplements

I read with great interest the review published by Eslamparast et al, on the dietary supplements with hepato-protective properties, and their proposed mechanisms to protect against non-alcoholic fatty liver disease. In this way, recently, our study group reported the efficacy of the Mediterranean diet associated to an antioxidant complex, to improve in overweight patientsnot only anthropometric parameters, but also insulinresistance, lipid serum levels, and intra-hepatic fat accumulation.

Pharmacotherapy of acute alcoholic hepatitis in clinical practice

Severe alcoholic hepatitis(AH)is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol.The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features,and several scoring systems.Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence.Liver transplantation is a possible therapeutic option for severe AH.Among the anti-craving medications able to improve abstinence rate,baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage.

Hepatitis C virus genotypes in north eastern Algeria: A retrospective study

AIM: To determine the frequency of various hepatitis C virus (HCV) genotypes present in patients from north eastern Algeria. METHODS: This is a retrospective cross-sectional study of 435 HCV infected patients from northeast Algeria, detected in the Sadelaoud laboratory and diagnosed between January 2010 and December 2012. The patients were diagnosed with HCV infection in their local hospitals and referred to be assessed for HCV genotype before the antiviral treatment. Demographic information (sex, age and address), genotype, subtype and viral load were retrieved from the patient medical records. The serum samples were tested by the type-specific genotyping assay.RESULTS: The majority of the patients (82.5%) were from the central part of the examined region (P = 0.002). The mean age of the patients studied was 53.6 ± 11.5 years. HCV genotype 1 was the most frequent (88.7%), followed by genotypes 2 (8.5%), 4 (1.1%), 3 (0.9%) and 5 (0.2%). Genotype 6 was not detected in these patients. Mixed infection across the HCV subtypes was detected in twenty patients (4.6%). The genotype distribution was related to age and region. Genotype 1 was significantly less frequent in the ≥ 60 age group than in the younger age group (OR = 0.2; 95%CI: 0.1-0.5, P < 0.001). Furthermore, genotype 1 was more frequent in the central part of the examined region than elsewhere (P < 0.01). CONCLUSION: The HCV genotype (type 1b was dominant) distribution in Algeria is different from those in other northern countries of Africa.

The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer

Currently, alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases worldwide, representing one of the main etiologies of cirrhosis and hepatocellular carcinoma (HCC). Although we do not know the exact mechanisms by which only a selected group of patients with ALD progress to the final stage of HCC, the role of the gut microbiota within the progression to HCC has been intensively studied in recent years. To date, we know that alcohol-induced gut dysbiosis is an important feature of ALD with important repercussions on the severity of this disease. In essence, an increased metabolism of ethanol in the gut induced by an excessive alcohol consumption promotes gut dysfunction and bacterial overgrowth, setting a leaky gut. This causes the translocation of bacteria, endotoxins, and ethanol metabolites across the enterohepatic circulation reaching the liver, where the recognition of the pathogen-associated molecular patterns via specific Toll-like receptors of liver cells will induce the activation of the nuclear factor kappa-B pathway, which releases pro-inflammatory cytokines and chemokines. In addition, the mitogenic activity of hepatocytes will be promoted and cellular apoptosis will be inhibited, resulting in the development of HCC. In this context, it is not surprising that microbiota-regulating drugs have proven effectiveness in prolonging the overall survival of patients with HCC, making attractive the implementation of these drugs as co-adjuvant for HCC treatment.

Probiotics supplementation in the management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC,also known as primary liver cancer),is the fourth most frequent cancer and the third cause of deaths associated with cancer worldwide(1).HCC occurs in liver damaged tissue,due to chronic regenerative and inflammatory processes that contribute to the initiation and progression of the tumor(2).The main environmental factors associated with HCC are hepatotropic viral infection(hepatitis B and C,particularly),excessive consumption of alcohol,and exposure to aflatoxin through the diet.However,in the last 20 years,non-alcoholic fatty liver disease(NAFLD)has become a quickly emerging cause of end-stage liver disease worldwide.Typically,its hepatic injury starts with simple steatosis,which can progress to advanced stages such as non-alcoholic steatohepatitis(NASH),fibrosis and finally cirrhosis.Epidemiology studies report that about 3-15%of the obese patients with NASH progress to cirrhosis,and about 4-27%of NASH patients with cirrhosis present HCC(1).

What Has the COVID-19 Pandemic Taught Us so Far?Addressing the Problem from a Hepatologist's Perspective

As of today, March 30, 2020, when this Editorial is being written, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19) has been confirmed in more than 745,000 cases worldwide and has claimed the lives of more than 35,000 people.1 In addition to the morbidity and mortality associated with COVID-19, this betacoronavirus has placed several of the world's major economies in strife, mainly in Western Europe and North America, paralyzing travel and regular social interactions, making COVID-19 undoubtedly one of the most important pandemics in human history.

SARS-CoV-2 and liver damage:a possible pathogenetic link

On December 31,2019,the World Health Organization(WHO)China Country Office,was informed of pneumonia cases of unknown etiology detected in Wuhan,a city of Hubei Province in China.

Are probiotics effective in reversing non-alcoholic steatohepatitis?

The gut microbiota(GM)is an integrated ecosystem of tens of trillions of microorganisms,as actinomyces,archaea,protozoa,and last but not least viruses,including one thousand different species of known bacteria with an overall count of more than three million genes,150 times more than the human genome.GM presents immune-modulating,absorptive and metabolic functions(1).

Beneficial effects of coffee in non-alcoholic fatty liver disease:a narrative review

Non-alcoholic fatty liver disease(NAFLD)is one of the most common liver diseases and is related to unhealthy lifestyle habits,characterized by a diet rich in sugars and fats leading to excessive calorie intake,and lack of exercise.In recent years,there is a growing incidence of this pathology,raising the attention of hepatologists,endocrinologists,diabetologists,and nutritionists.In this context,the alimentary regimen adopted by patients with NAFLD has become an increasingly scrutinised parameter.Diet is now considered a crucial factor in the treatment of NAFLD since it has been observed that some functional foods play a beneficial role.These include coffeewhose health effects have already been amply demonstrated.Here we describe the beneficial effects of coffee consumption reported in the NAFLD literature.

Nonalcoholic fatty liver disease in obese adolescents: the role of genetic polymorphisms

Nonalcoholic fatty liver disease(NAFLD)has recently become an emerging health problem worldwide(1).The pathogenetic mechanisms involved in the development and progression of NAFLD are due to genetic predisposition that expresses a metabolic profile associated with high energy food intake(2).The most accurate estimate of the worldwide prevalence of NAFLD is 24–25%of the general population,and ranges from 5–18%in Asia to 20–30%in the Western countries(1,3).Nowadays,the reason for this variability is not clear yet.However,it is plausible that genetic factors could play a major role in pathogenesis and the advances in genomics,transcriptomics,and proteomics have highlighted new pathogenic pathways.In fact,increasing literature data support the role of single nucleotide polymorphisms(SNPs),and in particular the SNPs of genes involved in insulin signaling,lipid homeostasis,and oxidative stress,not only in the susceptibility to develop NAFLD,but also in the severity of liver damage and in the etiology of multisystemic metabolic disorders(4).The development of the Genome Wide Association Study technology has allowed the identification of many SNPs involved in the onset of NAFLD,since they can change the stages of development,the rate of progression,and the efficacy of treatment(5).Recently,Tricòet al.investigate the clinical and genetic features associated with pediatric NAFLD in a prospective study in a large multiethnic cohort of obese adolescents(6).A total of 503 subjects,identified as"The Yale Pediatric NAFLD cohort",were enrolled,including 191(38.0%)Caucasians,134(26.6%)African Americans,and 178(35.4%)Hispanics.