Clinical assessment and management of liver fibrosis in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression of liver fibrosis.This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD,analyzing the currently available literature.In the assessment of NAFLD patients,it is important to identify clinical,genetic,and environmental determinants of fibrosis development and its progression.To properly detect fibrosis,it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores,followed by a complementary imaging study(transient elastography,magnetic resonance elastography or acoustic radiation force impulse)and finally a liver biopsy,when needed.To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review,describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis.Finally,treatment should always include diet and exercise,as well as controlling the components of the metabolic syndrome,+/-vitamin E,considering the presence of sleep apnea,and when available,allocate those patients with advanced fibrosis or high risk of progression into clinical trials.The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD,aiming to decrease/stop its progression and improve their prognosis.

Nutritional therapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most frequent primary liver cancer and presents together with cirrhosis in most cases.In addition to commonly recognized risk factors for HCC development,such as hepatitis B virus/hepatitis C virus infection,age and alcohol/tobacco consumption,there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat,type of cooking(generation of heterocyclic amines)and contamination of foods with aflatoxins.On the contrary,protective nutritional factors include diets rich in fiber,fruits and vegetables,n-3 polyunsaturated fatty acids and coffee.While the patient is being evaluated for staging and treatment of HCC,special attention should be paid to nutritional support,including proper nutritional assessment and therapy by a multidisciplinary team.It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis,and therefore they could present with severe malnutrition.Cirrhosisrelated complications should be properly addressed and considered for nutritional care.In addition to traditional methods,functional testing,phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment.Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer.Supplementation with branched-chain amino acids is also recommended as it improves response to treatment,nutritional status and survival,and finally physical exercise must be encouraged and adapted to individual needs.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is associated with complications and mortality in patients with coronavirus disease 2019(COVID-19).However,there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD,despite its high prevalence.Lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage.Therefore,we propose an index based on lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19.AIM To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases(aspartate aminotransferase/alanine aminotransferase)in patients with COVID-19 and MAFLD[liver fibrosis and nutrition(LNF)-COVID-19 index].METHODS In this retrospective cohort study,two cohorts from two different tertiary centers were included.The first was the derivation cohort to obtain the score cutoffs,and the second was the validation cohort.We included hospitalized patients with severe COVID-19 and MAFLD.Liver steatosis was evaluated by computed tomography scan.Area under the receiver operating characteristic(ROC)curve analysis and survival analysis were used.RESULTS In the derivation cohort,44.6%had MAFLD;ROC curve analysis yielded a LFN-COVID-19 index>1.67 as the best cutoff,with a sensitivity of 78%,specificity of 63%,negative predictive value of 91%and an area under the ROC curve of 0.77.In the multivariate analysis,the LFN-COVID-19 index>1.67 was independently associated with the development of acute kidney injury(odds ratio:1.8,95%confidence interval:1.3-2.5,P<0.001),orotracheal intubation(odds ratio:1.9,95%confidence interval:1.4-2.4,P<0.001),and death(odds ratio:2.86,95%confidence interval:1.6-4.5,P<0.001)in both cohorts.CONCLUSION LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19,which could be useful for the MAFLD population.

Clinical perspectives,assessment,and mechanisms of metabolicassociated fatty liver disease in patients with COVID-19

Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes,including mortality,in patients developing coronavirus disease(COVID-19).Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolicassociated fatty liver disease(MAFLD),a high number of cases of patients affected by both MAFLD and COVID-19 would be expected,especially in highrisk populations.Some studies have shown an increased risk of adverse clinical outcomes,viral shedding,and deep vein thrombosis,especially in patients with MAFLD-related liver fibrosis.The predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both,including preexisting systemic chronic inflammation,endothelial dysfunction,and involvement of the renin-angiotensin system.Because of the increased risk of adverse outcomes,MAFLD should be screened in all patients admitted for COVID-19.Available computed tomography scans could be of help,assessment of liver fibrosis is also recommended,favoring noninvasive methods to limit the exposure of healthcare workers.Liver involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem biopsies.Finally,preventive measures should be strongly advocated in patients already known to have MAFLD,including the use of telemedicine and vaccination in addition to general measures.

Clinical characteristics and treatment outcomes in patients with liver cirrhosis and lymphoma

BACKGROUND A significant number of patients with liver cirrhosis concomitantly develop some type of solid or hematological cancer,including lymphoma.Treatment of patients with lymphoma and cirrhosis is challenging for physicians due to the clinical characteristics related to cirrhosis,including biochemical and functional abnormalities,as well as portal hypertension and lack of scientific evidence,limiting the use of chemotherapy.Currently,experts recommend only offering oncological treatment to patients with compensated cirrhosis.AIM To evaluate the clinical characteristics and treatment outcomes in patients with cirrhosis and lymphoma treated with chemotherapy.METHODS This was a case-control study conducted at a tertiary care center in Mexico.Data was recorded from medical files and from 8658 possible candidates with cirrhosis and/or lymphoma(2000 to 2018).Only 23 cases had both diseases concomitantly;10 patients with cirrhosis and lymphoma(cases)met the selection criteria and were included,and 20 patients with lymphoma(controls)were included and matched according to age,sex,and date of diagnosis,type and clinical stage of lymphoma.All patients received treatment with chemotherapy.For statistical analysis,descriptive statistics,Shapiro-Wilk test,Mann-Whitney U test,chisquare test and Fisher's exact test were used.Survival was evaluated using Kaplan-Meier curves and Log-rank test.RESULTS There were differences in biochemical variables inherent to liver disease and portal hypertension in patients with cirrhosis.The most frequent etiology of cirrhosis was hepatitis C virus(50%);80%were decompensated,the median Child-Turcotte-Pugh score was 7.5(6.75-9.25),and mean Model for End-stage Liver Disease was 11.5±4.50.Regarding lymphomas,non-Hodgkin's were the most common(90%),and diffuse large B cell subtype was the most frequent,with a higher International Prognostic Index in the cases(3 vs 2,P=0.049).The chemotherapy regimens had to be adjusted more frequently in the case group(50%vs 5%,P=0.009).The complications derived from chemotherapy were similar between both groups(80%vs 90%,P=0.407);however,nonhematological toxicities were more common in the case group(30%vs 0%,P=0.030).There was no difference in the response to treatment between groups.Survival was higher in the control group(56 wk vs 30 wk,P=0.269),although it was not statistically significant.CONCLUSION It may be possible to administer chemotherapy in selected cirrhotic patients,regardless of their severity,obtaining satisfactory clinical outcomes.Prospective clinical trials are needed to generate stronger recommendations.