Getting Physical before a Medical Physical and How It Leads to Doctor Becoming Patient: A Curious Case of Transient Raised Transaminases

This case report sheds light on a curious case of rhabdomyolysis in an otherwise healthy twenty-eight-year-old male and its direct effect on liver function tests. This case report provides a fresh perspective on the doctor-patient dynamic where a medic becomes a doctor. Attention is also drawn to the mental and socioeconomic repercussions of having a health issue whilst applying for a home loan.

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases:A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.

Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention

AIM:To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.METHODS:Forty-six obese children, 21 males and 25females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography(US) and chemicalshift magnetic resonance imaging(MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index(BMI)was above the age- and sex-adjusted BMI Cole's curve passing through the cut-off of 30 kg/m2 at 18 years.BMI Z scores were calculated and adjusted for age and gender by using the Cole's LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence.The same radiologist performed US by a GE Logiq 9(General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemicalshift MRI with a 1-t system NT-Intera(Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction(FF) on MRI was judged elevated when greater than 9%. A FF>18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.RESULTS:Compared to baseline, at the end of intervention children showed lower intakes of energy(mean± SD:2549±1238 Kcal vs 1770±622 Kcal, P<0.0001), total fat(90±47 g vs 52± 23g, P<0.0001),carbohydrates(356±174g vs 241±111 g, P=0.001),and protein(99±48g vs 75±23g, P=0.006) intakes. Prevalence of FF≥9% declined from 34.8%to 8.7%(P<0.01), with a mean reduction of 7.8%(95%CI:5.0-10.6). At baseline, FF was associated with liver biochemical parameters(maximum P<0.001). At the end of the intervention association was found with AST(P=0.017). Change of FF was associated with change in AST(P =0.027) and ALT(P=0.024). Rate of increased liver echogenicity declined from 45.6% to21.7%(P<0.0001). Liver echogenicity was associated with ALT at baseline only(P<0.001). An age-and sexadjusted multiple regression analysis showed that FF change was independently associated with change in serum AST(adjusted regression coefficient 0.348, P=0.048).CONCLUSION:The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.

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.

Glutathione Reductase, Liver Transaminases and Atypical Lymphocytes Count as Early Predictive Biomarkers in Diagnosis of Thrombocytopenia in Dengue Viral Infection

Objective: The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. Methods: A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3rd and 5th day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). Results: GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). Conclusion: Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.

Investigation of minerals, testosterone, and transaminases in the semen and serum of fertile and infertile men belongs to different age groups

The present study was aimed to assess the potential of infertility to induce the adverse effects with reference to testosterone, Triiodothyronine (T3), Thyroxine (T4), Alanine Aminotransferase (ALT), Aspartate Amino-transferase (AST), zinc, copper and iron. All the samples were divided into four groups according to age and disorder (Group 1, 10 infertile men of 25-40 years;Group 2, 10 fertile men of 25-40 years;Group 3, 10 infertile men of 41- 60 years and Group 4, 10 fertile men of 41-60 years). Semen and blood samples were analyzed by atomic absorption spectrophotometry to determine minerals while, Testosterone, T3 and T4 were determined by enzyme immunoassay kits. ALT and AST were determined using standard kit assay method. The levels of testosterone and T3 and AST in the fertile semen of 41-60 years age group were increased significantly (P ≤ 0.001) as compared to that of fertile semen of 25-40 years age group. While, the level of T4 in the fertile semen of 41-60 years age group was decreased significantly (P ≤ 0.001) as compared to that of fertile semen of 25-40 years age group. In case of fertile serum, only the level of testosterone was significantly decreased (P ≤ 0.05) in the 41-60 years age group as compared to 25-40 years age group. The levels of testosterone and Cu in the infertile serum of 41-60 years age group were decreased significantly (P ≤ 0.001). While, the levels of T3, T4, ALT and Fe in the infertile serum of 41-60 years age group were increased significantly (P ≤ 0.05) as compared to that of infertile serum of 25-40 years age group.

A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients

AIM:To examine whether a dose-up to 900 mg of ursodeoxycholic acid(UDCA) decreases transaminases in hepatitis C patients.METHODS:From January to December 2007,patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus(HCV)(43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study.Blood parameters were examined at 4,8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d.RESULTS:Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT) levels were signifi cantly decreased following the administration of 900 mg/d as compared to 600 mg/d.The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L,while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L.Platelet count tended to increase after the dose-up of UDCA,although it did not show a statistically signifi cant level(P=0.05).Minor adverse events were observed in 3 cases,although no drop-outs from the study occurred.CONCLUSION:Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT,AST,and GGT levels in patients with HCV-related chronic liver disease.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

COVID-19-induced transaminitis and hyperbilirubinemia:Presentation and outcomes

The risk of liver injury in patients with coronavirus disease 2019(COVID-19)infection is quite evident.Furthermore,liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines.This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury,such as chronic liver disease,to elucidate COVID-19-induced liver function abnormalities and their severity,pathophysiology,clinical manifestations,and clinical and laboratory outcomes.We also discuss the effect of vaccination against COVID-19 to better understand host factors,such as age,gender,and race,on the incidence and severity of liver dysfunction at initial presentation and during the illness.Finally,we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.

COVID-19 and the liver:Are footprints still there?

The coronavirus disease 2019(COVID-19)hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases.An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems.It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction.Additionally,liver function abnormalities were noted in patients with severe COVID-19.Profound cytokine storm,direct viral infection,drugs and reactivation of viral infections were causes of deranged liver functions.Here,we discuss the relation between COVID-19 and chronic liver disease,specifically cirrhosis,hepatitis B,hepatitis C,and non-alcoholic fatty liver disease(NAFLD),as well as the liver manifestations of COVID-19.The metabolic syndrome,obesity,diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide.Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19.Recently,COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis.The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Pocket Modification of x-Amine Transaminase AtATA for Overcoming the Trade-Off Between Activity and Stability Toward 1-Acetonaphthone

Amine transaminases(ATAs)catalyze the asymmetric amination of prochiral ketones or aldehydes to their corresponding chiral amines.However,the trade-off between activity and stability in enzyme engineering represents a major obstacle to the practical application of ATAs.Overcoming this trade-off is important for developing robustly engineered enzymes and a universal approach for ATAs.Herein,we modified the binding pocket of co-ATA from Aspergillus terreus(AtATA)to identify the key amino acid residues controlling the activity and stability of AtATA toward 1-acetonaphthone.We discovered a structural switch comprising four key amino acid sites(R128,V149,L182,and L187),as well as the"best"mutant(AtATAD224K/V149A/L182 F/L187F;termed M4).Compared to the parent enzyme AtATAD224K(AtATAPa),M4 increased the catalytic efficiency(k_(cat)/K_(m)^(1-acetonaphthone),where kcatis the constant of catalytic activities and is 10.1 min^(-1),K_(m)^(1-acetonaphthoneis) Michaelis-Menten constant and is 1.7 mmol·L^(-1))and half-life(t1/2)by 59-fold to 5.9 L·min^(-1)·mmol-1and by 1.6-fold to 46.9 min,respectively.Moreover,using M4 as the biocatalyst,we converted a 20 mmol·L^(-1)aliquot of 1-acetonaphthone in a 50 mL scaled-up system to the desired product,(R)-(+)-1(1-naphthyl)ethylamine((R)-NEA),with 78%yield and high enantiomeric purity(R>99.5%)within 10 h.M4 also displayed significantly enhanced activity toward various 1-acetonaphthone analogs.The related structural properties derived by analyzing structure and sequence information of robust ATAs illustrated their enhanced activity and thermostability.Strengthening of intramolecular interactions and expansion of the angle between the substratebinding pocket and the pyridoxal 5’-phosphate(PLP)-binding pocket contributed to synchronous enhancement of ATA thermostability and activity.Moreover,this pocket engineering strategy successfully transferred enhanced activity and thermostability to three other ATAs,which exhibited 8%-22%sequence similarity with AtATA.This research has important implications for overcoming the trade-off between ATA activity and thermostability.

Effects of Purified Indian Cattle Tick Rhipicephalus microplus Saliva Toxins on Various Enzymes in Blood Serum, Liver and Muscles of Albino Mice

In the present investigation, in vivo effects of purified ticks’ saliva toxin were evaluated on the level of certain important cellular metabolic enzymes i.e. acid phosphatase (ACP), alkaline phosphatase (ALP), glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and lactic dehydrogenase. For this purpose, sub-lethal doses, 40% and 80% of 24 h LD50 purified saliva toxins of Rhipicephalus microplus (Canestrini, 1888) were injected subcutaneously in the albino mice. In treated mice saliva toxins targeted membrane-bound enzymes i.e. serum acid phosphatase and alkaline phosphatase, its level was increased from 118.30% to 163.63% at the 6th hr in comparison to the control. Besides this, the levels of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) and lactic dehydrogenase (LDH) also increased up to 161.11% (at 6th hr), 148.27 (at 8th hr) and 125.45% (at 6th hr) respectively in comparison to control. An increase in the level of LDH showed insufficient oxygen supply, massive disintegration of cells and leakage of the enzyme into the circulation. It clearly indicated the toxic effects of saliva toxins on the membrane of blood cells, hepatocytes and myocardial muscle cell functions in albino mice. On the other hand activity of acetyl cholinesterase was reduced by 65.51% at the 6th hr of the saliva toxin injection in comparison to the control. This inhibition of acetyl cholinesterase activity caused the accumulation of acetylcholine molecules at the synaptic junctions and led to prolonged activation of acetylcholine receptors. It caused permanent stimulation of nerves and muscle cells that may result in muscular paralysis and finally death of the animal.

Effect of Purified Paper Wasp Ropalidia marginata Venom Toxin Enzyme Activity in Blood Serum, Liver, and Gastrocnemius Muscle of Albino Mice

In the present, investigation effects of sub-lethal dose of purified paper wasp Ropalidia marginata venom toxins were evaluated on important metabolic enzymes i.e. ALP ACP, GPT, GOT, LDH, and AchE enzyme activity in serum, liver, and gastrocnemius muscles of albino mice. Alkaline phosphatase was found to be increased up to 119.9% at the 6th hr of the toxin injection in comparison to control. This elevation may be due to cytolysis. Maximum increase i.e., 153.33% level of glutamate pyruvate transaminase (GPT) was found at 6 hrs of 40% of 24-h LD50 treatment while it was found to be 151.1% at 6 hrs of 24 hr 80% of LD50, venom injection. A significant elevation was observed in LDH activity in serum, liver, and muscles, while the activity of AchE was decreased in serum, liver, and gastrocnemius muscles of albino mice after injecting the sub-lethal dose of Ropalidia marginata venom. This increase in the activity of LDH produces liver damage, massive disintegration and necrosis of hepatic cells. This elevation in LDH level led to a significant increase in the glucose catabolism and elevated oxidative stress in muscle and liver cells. It also displays insufficient oxygen supply and consequently leads to cell death. In experimental animals, venom toxin treatment decreased AchE level, and animals showed muscular paralysis. When mice were treated with 40% and 80% of 24-h LD50 of purified venom caused a significant (p < 0.05) elevation in the level of ACP, GOT, GPT, and LDH while the reduction in ALP and AChE level. Present study will be useful in the development of prototypes for study of pharmacological and therapeutic effects of various venom toxins. For this purpose structure activity relationship of enzyme and venom toxin, its due interaction to various metabolic enzymes and receptors must be explored.

Liver enzymes,metabolomics and genome-wide association studies:From systems biology to the personalized medicine

For several decades,serum levels of alanine(ALT) and aspartate(AST) aminotransferases have been regarded as markers of liver injury,including a wide range of etiologies from viral hepatitis to fatty liver.The increasing worldwide prevalence of metabolic syndrome and cardiovascular disease revealed that transaminases are strong predictors of type 2 diabetes,coronary heart disease,atherothrombotic risk profile,and overall risk of metabolic disease.Therefore,it is plausible to suggest that aminotransferases are surrogate biomarkers of "liver metabolic functioning" beyond the classical concept of liver cellular damage,as their enzymatic activity might actually reflect key aspects of the physiology and pathophysiology of the liver function.In this study,we summarize the background information and recent findings on the biological role of ALT and AST,and review the knowledge gained from the application of genome-wide approaches and "omics" technologies that uncovered new concepts on the role of aminotransferases in human diseases and systemic regulation of metabolic functions.Prediction of biomolecular interactions between the candidate genes recently discovered to be associated with plasma concentrations of liver enzymes showed interesting interconnectivity nodes,which suggest that regulation of aminotransferase activity is a complex and highly regulated trait.Finally,links between aminotransferase genes and metabolites are explored to understand the genetic contributions to the metabolic diversity.

Establishment of 6VS Telocentric Lines of Haynaldia villosa Resistant to Powdery Mildew Induced by Immature Embryo Culture

The line of T240-6 was selected from 32 SC 2 lines of immature embryo culture of T240 (common wheat (Triticum aestivum L.)× Wheat-Haynaldia villosa (L.) Schur. 6D/6V substitution line) through powdery mildew characterization, glutamate oxaloacetate transaminase (GOT) enzyme and gliadin (Gli) analyses and in situ hybridization. All of the individual plants resistant to powdery mildew lacked the locus of GOT at 6VL arm (GOT-V 2) and had gliadin locus at 6VS arm (Gli-V 2) of Haynaldia villosa. All the plants resistant to powdery mildew had one or two telocentric chromosomes that did not pair with wheat chromosomes but paired between themselves. T240-6 was identified as a telocentric line through in situ hybridization.

Dengue and its effects on liver

Dengue has emerged as an important arboviral disease with significant impact on the disease burden in population residing in tropical countries. Dengue is spread by the bite of Aedes mosquito. The virus seems to have some hepatotoxic effects. Affliction of liver in form of derangements in the liver function tests is common and may include mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin. Although asymptomatic in most cases, clinical manifestations like jaundice, and acute liver failure(ALF) may occasionally complicate the clinical picture. Indeed, dengue has been implicated as an important cause of ALF in endemic countries. The present review focuses on the hepatic manifestations and the pathogenesis of the liver injury in dengue.

Risk of liver disease in methotrexate treated patients

Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.

Lipid-lowering agents in the management of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.