Cause Of Elevated Liver Enzymes Research Articles

Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat?

Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.

Diagnostic Approach to Elevated Liver Function Tests during Pregnancy: A Pragmatic Narrative Review.

Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30-40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy.

Liver injury in patients with COVID-19 in comparison to patients with the pandemic influenza A (H1N1) 2009: a population-based study

Background Elevated liver tests in patients with COVID-19 are widely reported. Population-based studies utilizing a validated analysis of drug-induced liver injury (DILI), with a control group of other viral illnesses and follow-up are largely lacking. Materials and methods All hospitalized patients in Iceland with SARS-CoV-2 in 2020 and pandemic influenza A (H1N1) in 2009 were included in this retrospective, population-based study. Liver tests were compared between the two groups and the correlation to inflammatory markers and persistence of alanine aminotransferase (ALT) elevations were assessed. Potential DILI cases were reviewed using the Roussel Uclaf Causality Assessment Method (RUCAM). Results 225 SARS-CoV-2-positive and 73 influenza A (H1N1)-positive patients were included. Liver test values were similar between the groups, except for aspartate aminotransferase (AST) which was significantly lower in COVID-19, with a mean difference of 26 U/L (95%CI 4.2-47). Ferritin elevation was positively correlated with ALT, AST and alkaline phosphatase. No patient had persistently elevated ALT in COVID-19 and none had a probable DILI. Only 3 patients had a possible DILI according to the RUCAM. Conclusions Elevated liver enzymes are not specific for COVID-19. Hyperferritinemia was associated with elevated liver tests. DILI was very rare in COVID-19 and an unlikely cause of elevated liver enzymes in COVID-19. Abnormal liver tests are nonpersistent and generally not clinically important in these patients.

Non-alkolik yağlı karaciğer hastalığında kafein alımı ve karaciğer biyobelirteçleri arasındaki ilişki

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in developed countries. The aim of this study is to examine the effects of caffeine intake on some parameters of liver metabolism in individuals with NAFLD.
 Materials and Methods: A total of 20 female and 20 male subjects between the ages of 19 to 64, who were diagnosed with NAFLD, were included in the study. To determine caffeine intake, a specially developed caffeine-food frequency questionnaire was administered by a trained dietitian. Individuals were categorized into 3 groups according to their caffeine intake; Group 1: ≤150 mg/day, Group 2: 150-250 mg/day, and Group 3: ≥250 mg/day. Anthropometric measurements and biochemical parameters were recorded. Protein quantities in serum samples were determined by ELISA method.
 Results: The body fat composition of group 1 was higher than group 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of group 3 were higher than group 1 and group 2, respectively. High-density lipoprotein cholesterol (HDL-C) level of group 3 was lower than group 1 and group 2. There was a positive correlation between total caffeine intake and ALT level. There was no significant difference between the caffeine intake groups in terms of serum protein levels. In addition, there was not found significant correlation between serum protein levels and total caffeine intake.
 Conclusion: Caffeine intake of ≥250 mg/day may increase ALT and AST levels and decrease HDL-C level in individuals with NAFLD.

Utility of Doppler-Ultrasound and Liver Elastography in the Evaluation of Patients with Suspected Pregnancy-Related Liver Disease

Grayscale abdomen ultrasound (US) is routinely performed in pregnant women with suspected pregnancy-related liver dysfunction, but its diagnostic yield is very low. We aimed to investigate the association between Doppler-US findings, liver stiffness measurement (LSM) and different causes of pregnancy-related liver dysfunction. This is a prospective cohort study of pregnant women referred to our tertiary center for any suspected gastrointestinal disease between 2017 and 2019 and undergoing Doppler-US and liver elastography. Patients with previous liver disease were excluded from the analysis. For group comparisons of categorical and continuous variables, the chi-square test or Mann-Whitney test, and the McNemar test were used, as appropriate. A total of 112 patients were included in the final analysis, of whom 41 (36.6%) presented with suspected liver disease: 23 intrahepatic cholestasis of pregnancy (ICP), six with gestational hypertensive disorders and 12 cases with undetermined causes of elevated liver enzymes. Values of LSM were higher and significantly associated with a diagnosis of gestational hypertensive disorder (AUROC = 0.815). No significant differences at Doppler-US or LSM were found between ICP patients and controls. Patients with undetermined causes of hypertransaminasemia showed higher hepatic and splenic resistive indexes than controls, suggesting splanchnic congestion. The evaluation of Doppler-US and liver elastography is clinically useful in patients with suspected liver dysfunction during pregnancy. Liver stiffness represents a promising non-invasive tool for the assessment of patients with gestational hypertensive disorders.

S2974 Common Variable Immune Deficiency With Atypical Hepatic Disease

Introduction: Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder leading to hypogammaglobulinemia. Liver involvement may rely on immune dysregulation and includes abnormal liver biochemistries, primarily elevation of alkaline phosphatase (ALP), nodular regenerative hyperplasia (NRH) leading to chronic cholestasis, portal hypertension, and disruption of liver function. We present a case of CVID with atypical liver involvement on imaging and biopsy revealing focal nodular hyperplasia. Case Description/Methods: A 24-year-old female with a past medical history of CVID on Intravenous immunoglobulin (IVIG) present for follow-up with chronically elevated liver enzymes that is a cholestatic pattern (ALP 1050 U/L, AST 114 U/L, ALT 214 U/L, Total bilirubin 1.0 mg/dL) along with normal synthetic liver function. Previous comprehensive work up including autoimmune (Antinuclear, Anti-smooth muscle, anti-mitochondrial antibodies) were negative. Viral hepatitis including Hepatitis B, Hepatitis C, Herpes simplex, Varicella zoster, and Epstein Barr viruses polymerase chain reaction were all negative. other causes of elevated liver enzymes including genetic and metabolic work up all came back negative. The medications list included Ursodiol and Multivitamins. She reports no alcohol, recreational or herbal drugs use. She underwent liver protocol magnetic resonance imaging and magnetic resonance cholangiopancreatography that showed no biliary tree abnormalities, Innumerable hepatic lesions with characteristics suggestive of multiple focal nodular hyperplasias largest measures up to 3.8 cm, two benign hepatic hemangiomas with the larger measuring 1.9 cm and splenomegaly. Ultrasound-guided biopsy of the left hepatic lobe showed concern for focal nodular hyperplasia (confirmed by an outside pathologist at another liver transplant center) with unremarkable trichrome and PAS stains (Figure). Discussion: At least 10% of CVID patients present with liver involvement, including anicteric cholestatic liver enzymes (65%) and portal hypertension (50%). Histological analysis in recent studies revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia in 84% of CVID and less commonly, typical histologic features of primary biliary cholangitis. Our case liver imaging and biopsy read by 2 pathologists (2 institutions) revealed focal nodular hyperplasia, a new entity not described in previous studies.Figure 1.: Liver protocol MRI showing focal nodular hyperplasia.

A case of acute hepatitis associated with COVID-19 in a geriatric patient

Coronavirus 2019 disease (COVID-19) is a deadly disease that causes 44 million positive cases and over 1 million deaths worldwide. COVID-19 is a disease in which respiratory tract infectious diseases such as fever, shortness of breath, and cough are observed more frequently. It has been observed to cause liver damage in literature studies in addition to respiratory symptoms. Our case is a 77-year-old male having no systemic disease except hypertension. Fever of 38.2°C for four days, pulse 84/min, respiratory rate 18/min, blood pressure 136/82 mmHg, and oxygen saturation on room air was measured 92% by pulse oximetry. The patient who had aspartate aminotransferase (AST) 753 IU/L and alanine aminotransferase (ALT) 683 U/L in the tests in the emergency room was admitted to the infectious diseases service because of acute liver damage and the positive result of the COVID-19 PCR-RT test performed in the emergency department. The diagnosis of acute hepatitis associated with COVID-19 was made in our case, after excluding other causes of elevated liver enzymes. We aimed to contribute to the literature by presenting our case.

S2568 DDD: Diagnostic Dilemma in Drug Induced Liver Injury: Adverse Reaction of Abiraterone in Treatment of Metastatic Prostate Cancer

INTRODUCTION: Drug-induced liver injury (DILI) is a benign and reversible form of liver injury that occurs as an adverse reaction to medication use. It is a leading cause of acute liver failure and requires prompt recognition and discontinuation of the offending agent to avoid development of chronic disease. We present a case of severe DILI secondary to Abiraterone use in a patient with prostate cancer. CASE DESCRIPTION/METHODS: A 67 year-old-male without known liver disease was seen for severely elevated liver enzymes, jaundice and abdominal pain. Pertinent history includes stage IV prostate cancer with metastasis to the bone and lymph nodes with initiation of Abiraterone four months prior. He denies excessive alcohol, acetaminophen or herbal supplement use. Initial liver panel results: AST 1668 (peak 2379), ALT 3093 (peak 3330), alk phos 185 (peak 361) and TB 14.3 (peak 29). INR was 1.40 (peak 1.65). While transplant center transfer was considered, given patient's stability and not meeting King's College Criteria for acute liver failure, this decision was deferred and he was placed on NAC for 48 hours. Extensive workup for other causes of elevated liver enzymes were negative including: Wilson’s disease, autoimmune hepatitis, HAV, HBV, HCV, EBV, HSV, CMV, alpha 1 antitrypsin deficiency, portal vasculature thrombosis and acetaminophen toxicity. Core needle biopsies revealed acute hepatitis with confluent and bridging necrosis as well as mild Kupffer cell siderosis with iron accumulation. Serum ferritin level was 28,441 and IgG4 was mildly elevated, which prompted concern for hemophagocytic lymphohistiocytosis(HLH), hemochromatosis and autoimmune cholangiopathy. Patient did not meet criteria for HLH, hemochromatosis types I-IV in the absence of HFE, HFE2, TFR2, HAMP and SLC40A1 gene mutations, nor did MRI or pathology staining reveal IgG4 cholangiopathy. LFTs normalized within four months and ferritin within six months. Abiraterone was not restarted. DISCUSSION: Abiraterone is an antiandrogen that inhibits CYP17. Although the mechanism of hepatic injury is unknown, Abiraterone has been shown to cause elevations in serum aminotransferase levels in up to 13% of patients and ALT elevations above 5x the ULN in 6% of patients, however only few documented cases are known in which patients displayed associated symptoms such as jaundice and no documentation of severe elevations in serum ferritin as seen in our patient. This case also highlights the diagnostic challenge in DILI.Figure 1.: A. Mild to moderate predominantly lymphocytic inflammation. B. Intact bile ducts.Figure 2.: Confluent necrosis with areas of bridging necrosis.Figure 3.: Iron stain with Kupffer cell siderosis.

Correlation of Liver Function Test with Different Age and Sex Group and with Ferritin Level in Thalassemia

Thalassemia is the most common genetic blood disease in the world and varies in different population group in the world. In thalassemic patients liver damage is augmented when age of the patients are increase. These are due to increasing age with advancement of disease progression, repeated blood transfusion, less use/ intolerance of iron chelating agent, decreased activity of hepatocyte to rescue them in such excess billirubin and iron flood. Secondary to hypersplenism. Iron overload due to frequent transfusions in ?-thalassemia results in abnormal organ function tests. Proper and timely screening of these parameters can help in early diagnosis & prevention of iron overload. Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload14. Liver injury whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST). In transfusion dependent thalassemia patients iron overload is often inevitable and exposed to transfusion associated infections. Apart from these when the age is more, the disease progresses with their complication like hepatic injury. The thalassemia patient develops liver fibrosis as a result of iron overload due to excessive blood transfusion and also from excess intestinal absorption. N Sultana et al.6 showed that serum ferritin and serum bilirubin parameter of iron over load and jaundice are correlated.

3168 Acute Liver Failure, Rhabdomyolysis, and Acute Kidney Injury Secondary to Influenza A Infection

INTRODUCTION: Influenza A is considered a self-limiting pulmonary infection with a constellation of respiratory symptoms. However, it is sometimes associated with unfortunate complications with high morbidity and mortality. We present a case who suffered from rhabdomyolysis, acute kidney injury, and acute liver failure secondary to influenza infection. CASE DESCRIPTION/METHODS: A 22-year-old male presented with red urine for one day associated with muscle pain in the thighs, back, neck, and extremities. He also had fever, chills, sore throat, and dry cough for 4 days. Past medical and surgical histories were unremarkable. Family history was insignificant. He did not take medications. He denied cigarette, alcohol, or IV drug use. He denied headache, nausea, vomiting, diarrhea, chest pain, hematemesis, or hemoptysis. On exam, the patient was in no acute distress. Vital signs were within normal limits. Abdominal exam showed a soft, non-tender, and non-distended abdomen without organomegaly. Initial testing revealed an elevated creatinine of 2.02 mg/dL. Urinalysis was significant for the presence of blood, but RBC count was 0/HPF. CK was elevated at 407,176 U/L and myoglobin elevated at 33,673 ng/ml. AST was elevated at 1540 U/L and ALT at 286 U/L. Respiratory pathogen panel was positive for influenza A. The patient's acute kidney injury was believed to be secondary to rhabdomyolysis. Extensive testing to look for the cause of elevated liver enzymes came back negative including viral hepatitis, iron studies, HIV, liver ultrasound, and abdominal CT. Similarly, no cause for rhabdomyolysis was found and autoimmune workup was negative. The patient's labs continued to worsen over his hospital course. His creatinine peaked at 8.69 mg/dL and he eventually needed dialysis. His CK continued to trend up and peaked at 1,271,160 U/L. His liver enzymes also trended up with AST peaking at 4100 U/L and ALT at 1043 U/L. Eventually, his liver enzymes and CK trended down to normal levels and he did not require liver transplantation. Unfortunately, his kidney function did not completely recover, and he still required dialysis. DISCUSSION: Although rare, extrapulmonary involvement of influenza A infection can happen and rhabdomyolysis is exceedingly rare. In our case, rhabdomyolysis was believed to be due to influenza A infection. As a result, he developed acute kidney injury requiring dialysis. His acute liver failure was believed to be multifactorial secondary to influenza infection and/or rhabdomyolysis.

The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) are the most common causes of elevated liver enzymes in the general population. NASH, and to a lesser extent NAFLD have been associated with increased liver-related, cardiovascular disease (CVD), and allcause mortality. No effective treatment is widely acceptable. The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH. A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH. Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial. Post hoc data from three large prospective randomized clinical trials (n>11, 000) suggest that specific statins (mainly atorvastatin) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function. Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH. Statin treatment may also protect from hepatocellular carcinoma (HCC) related to NAFLD/NASH. Since NAFLD/NASH patients have high CVD risk, they will probably require a statin. Thus, why not select a specific statins (atorvastatin or rosuvastatin, both generic now) that offer a substantial liver- and CVDrelated adverse event reduction? The administration of statins in these patients is as safe as in the general population.

Caffeine consumption and biochemical parameters in non-alcoholic fatty liver disease

Rationale: Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the most common cause of elevated liver enzymes in developed countries. The aim of this study is to evaluate caffeine intake and biochemical parameters in NAFLD.

Hyperthyroidism induced reversible hepatotoxicity a case report and brief review

The patients presenting with high liver enzymes have multiple etiologies ranging from hepatotoxic viruses, drugs, and various toxins. While viral hepatitis continues to be the leading cause of elevated liver enzymes, other metabolic and endocrine disorders also lead to elevated liver enzymes in a given patient. There is a paucity of data regarding hyperthyroidism and the high liver enzymes. We present the clinical scenario in a young male who presented with jaundice without viral prodrome or offending drug intake. The patient had no high-risk behavior, and on evaluation, he had negative viral serologies. Autoimmune profile was negative as well. The physical examination was suggestive of irregular pulse and normal blood pressure. On further evaluation hyperthyroidism was unraveled. Following treatment with antithyroid medication, the liver enzymes in the index case settled, and he had full clinical recovery, explaining the cause and effect relationship. Report on this case and brief literature review is presented. A good clinical examination often is a lead to the cause of disease and in a Jaundiced patient, hyperthyroidism can be one of the causes of high liver enzymes which must be ruled out in a given setting.

Challenges in Screening for Pediatric Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in children in the United States. Screening for NAFLD in children with obesity is recommended by several published guidelines, but the application of these recommendations in pediatric weight management programs is uncertain. Our study aimed to describe the screening practices for NAFLD in a large pediatric weight management program. During 2014, 1312 patients were seen, with a liver enzyme panel obtained in 847 (64.5%). Only 47/847 (5.5%) had elevated liver enzymes twice the upper limit of normal. Of the 47, 33 (70%) patients had persistently elevated liver enzymes. Of those 33, 22 (67%) had further exclusionary laboratory testing. Screening for NAFLD is challenging even in a pediatric weight management program with clearly established protocols. Those with elevated liver enzymes do not always complete recommended exclusionary testing. Barriers to completing further evaluation need to be addressed.

Hepatic manifestation of a macrophage activation syndrome (MAS)

Background Elevated liver values are the most common pathological laboratory result in Germany. Frequent findings, especially in younger patients, are nutritive- or medicamentous- toxic reasons, viral or autoimmune hepatitis. A macrophage activation syndrome (MAS) may manifest like a viral infectious disease with fever, hepatosplenomegaly and pancytopenia and is associated with a high mortality. It is based on an enhanced activation of macrophages with increased cytokine release, leading to organ damage and multi-organ failure. In addition to genetic causes, MAS is commonly associated with infections and rheumatic diseases. We report the case of a 26-year-old female patient suffering from MAS as a rare cause of elevated liver enzymes. Methods Patient characteristics, laboratory values, liver histology, bone marrow and radiological imaging were documented and analyzed. Case Report After an ordinary upper airway infection with bronchitis, a rheumatic arthritis appeared and was treated with leflunomide und methotrexate. In the further course of the disease, the patient developed an acute hepatitis with fever, pancytopenia and massive hyperferritinemia. Immunohistochemistry of the liver biopsy revealed hemophagocytosis and activation of CD68-positive macrophages. In the radiological and histological diagnostics of the liver and bone marrow, an MAS was diagnosed as underlying disease of the acute hepatitis. Under therapy with prednisolone, the fever disappeared and transaminases and ferritin rapidly normalized. Conclusion Aside from the frequent causes of elevated liver values in younger patients, such as nutritive toxic, drug induced liver injury, viral or autoimmune hepatitis, especially in case of massive hyperferritinemia, a MAS should be considered as a rare cause of acute liver disease.

Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a “hot potato” for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.

Liver Enzymes in Children with beta-Thalassemia Major: Correlation with Iron Overload and Viral Hepatitis

BACKGROUND:Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST).AIM:Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes.PATIENTS AND METHODS:Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients.RESULTS:Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group.CONCLUSION:Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload.

Gender and racial differences in nonalcoholic fatty liver disease

Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.

Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear. To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date. All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used. When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials. Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.

Primary Care Management of Non-Alcoholic Fatty Liver Disease at the Atlanta VA Medical Center: A Quality Improvement Project

Purpose: Non-alcoholic fatty liver disease (NAFLD) and its severe clinical form, non-alcoholic steatohepatitis (NASH), are becoming increasingly prevalent in the U.S., along with the epidemic of obesity. It has been recommended that weight loss, exercise, reduction of sedentary lifestyle, and dietary changes should be implemented as first-line therapy, ideally on a long-term basis, in all patients. Primary care physicians (PCPs) who are at the first-line of management of patients with hepatosteatosis have a crucial role in diagnosing and managing this condition. The aim of this study was to determine the quality of care provided by PCPs for patients with NAFLD, who visited the Atlanta VA hospital. Methods: We retrospectively reviewed the charts of 100 veterans who visited with their PCP between October, 2011 and October, 2012 with a diagnosis of elevated liver enzymes on routine blood testing. PCP notes were carefully reviewed to look at the work-up and management for NAFLD, including if liver imaging was ordered, monitoring weight loss, counseling for exercise, dietary intervention, referral to GI specialist, and primary care follow-up intervals. Patients with history of alcohol abuse and chronic viral hepatitis were excluded. Results: Of the 100 patients we reviewed, 70 had the diagnosis of NAFLD based on some imaging modality. In 70% of the notes, exercise counseling was documented; 75% documented dietary counseling, and 66 % documented weight loss counseling. However, the objective amount of weight loss from the time of diagnosis to the most recent weight was only 1%. Thirty-five percent documented referral for dietary counseling to a nutritionist, and only 5% were referred to hepatology. Two percent of the PCPs arranged a visit specifically to discuss lifestyle modification as the primary objective. Conclusion: NAFLD is the most common cause of elevated liver enzymes in the U.S. According to AASLD, loss of at least 3-5% of body weight appears necessary to improve steatosis, but up to 10% may be needed to improve inflammation. In our patient cohort, although over half of the PCPs documented weight loss, dietary, and exercise counseling, the majority of patients were not meeting even the minimum weight loss goal. The PCP's ability to sustain the change in lifestyle and maintain patient compliance with weight loss, diet, and exercise is sub-optimal. PCPs should consider setting more objective weight loss goals, arranging patient visits specifically to discuss life style modification, and use a multidisciplinary approach to patients with NAFLD, including referral to nutrition and hepatology. Quality improvement measures need to be taken that will facilitate optimization of treatment delivery to this group of patients, soas to prevent the complications of cirrhosis and HCC.