Abnormal Liver Tests Research Articles

Treatment of NAFLD with Adjustable Gastric Band Placement

Purpose: Nonalcoholic fatty liver disease is the most common liver disorder in the industrialized world, affecting 20-40% of the general population. Despite its high prevalence, there is no effective treatment other than weight loss. Often these patients have trouble losing weight through conventional methods and over 20% of patients progress to cirrhosis. Laparoscopic adjustable gastric band (AGB) is the least invasive surgical technique for treatment of medically-complicated obesity and the most commonly performed weight loss surgery in Europe. We report a case of a morbidly obese patient with advanced hepatic fibrosis secondary to NAFLD who had reversal of her liver disease after losing weight as a result of AGB placement. This is a 50 year old Hispanic female with a 29 year history of obesity who presented to the ER with right sided abdominal pain, nausea, and vomiting. Physical exam was pertinent for morbid obesity (BMI 38) and right sided abdominal tenderness. Blood work revealed platelets - 131,000, ALT- 148, AST-121 and ALP-167. CT scan of the abdomen showed splenomegaly. Past medical history included diabetes, osteoarthritis, and hyperlipidemia. Patient's morbid obesity was refractory to diets, liposuction, behavior modification, and medications. Patient was discharged two days later for outpatient follow-up of her abnormal liver tests. Complete liver work-up including viral serologies, autoimmune markers, iron studies, ceruloplasmin and antimitochondrial antibody were negative. Liver biopsy revealed chronic portal inflammation, mild to moderate fatty infiltration and stage 3-4 bridging fibrosis. Based on history, blood work, and liver biopsy, she was diagnosed with NAFLD. Subsequently, patient had an AGB placed laparoscopically for treatment of morbid obesity. Following band placement, patient successfully lost weight and this was directly associated with a downward trend in her transaminases. One year after AGB placement patient has lost 32% of her excess body weight with a current BMI of 31. Her transaminases are now within normal limits with AST- 26 and ALT-35. NAFLD is a progressive disease with significant morbidity and mortality due to development of cirrhosis. Routine attempts at losing weight with exercise, behavior modification, dieting, and medications are unsuccessful in these patients. Our case presents AGB placement as a successful intervention for induction of weight loss and prevention of ongoing hepatocellular injury in morbidly obese patients with NAFLD. With the advent of AGB as a minimally invasive weight loss surgery with effective results, we encourage the medical community to consider it as an early intervention for patients with morbid obesity and advanced NAFLD.

71 Outcomes and Clinical Effects From the Pediatric Ingestion of the Cholesterol Medication Fenofibrate

Fenofibrate (Tricor, Triglide, Antara) has wide adult use in United States. It is used with a low-fat diet and other medications to reduce the amounts of cholesterol and triglycerides in the blood by activation of the PPARa receptor. Through this mechanism, it increases lipolysis and elimination of triglyceride-rich particles from plasma. Documented side effects of the fenofibrate include abnormal liver tests, abdominal and back pain, and GI upset. These effects have been seen in adults, but there are no published studies evaluating the adverse effects of fenofibrate in the pediatric population. To study the clinical effects of accidental fenofibrate ingestion by young children. A retrospective, observational study of exposures to fenofibrate from January 2005 through November 2009 for children age 6 and younger, as documented by 1 state's poison center calls. There were 56 children who met the inclusion criteria. They were 11 months to 6 years in age. Ingestion doses ranged from 48 mg to 400 mg. Forty-nine children (87.5%; 95%CL: 76.4%-93.8%) were asymptomatic. The most common symptoms were GI in nature and included nausea/vomiting (3.5%), and diarrhea (3.5%). Other symptoms included drowsiness (1.8%) and black stool (1.8%). Thirty-six (64.3%) were managed at home with food, water, and observation. Eighteen (32.1%; 95%CI: 21.4%-45.2%) were managed at health care facilities. Of those treated in health care facilities, 10 were given 1 dose of activated charcoal. Only 6 (10.7%; 95%CI: 5.0%-21.5%) were admitted for additional observation, none to the ICU. All patients who were admitted were discharged with no additional treatment after less than 24 hours. There were 2 siblings who ingested the largest amount of the drug, 400 mg each, who were monitored at home and experienced no reported symptoms . This is the first large study of the adverse effects following the pediatric ingestion of fenofibrate. The large majority of these children were asymptomatic. However, low numbers, inconsistent follow-up, and reliance on caller information limit this study. All children documented had good outcomes (100%; 95%CI: 93.5%-100%), although 1 did leave the health care facility against medical advice and his outcome is unknown. Most of these ingestions may be managed at home, with even the symptomatic children doing well without limited intervention. More studies are needed to determine appropriate emergency management of ingestions in this age group.

Liver involvement in juvenile systemic lupus erythematosus (SLE)

Abnormal liver tests are common among adult patients with systemic lupus erythematosus (SLE). The most common cause is drug-induced hepatitis, while mild, predominantly lobular, but sometimes also portal and periportal-hepatitis reflecting SLE activity, is another possibility. Little is known about liver disease in juvenile SLE patients although mild transient liver enzyme abnormalities are noted in up to 25%.

Characteristics of Idiosyncratic Drug‐induced Liver Injury in Children

The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established. The DILIN (Drug-Induced Liver Injury Network) Prospective Study is a longitudinal multicenter study designed to determine the etiologies, risk factors, and outcomes of suspected DILI. Between September 2004 and September 2009, 30 children ages 2 to 18 years with suspected DILI who met eligibility criteria were enrolled and studied for at least 6 months. Mean age was 14 years; 70% were girls. Antimicrobial (50%) and central nervous system agents (40%) were the most commonly implicated drug classes, with minocycline (4), isoniazid (3), azithromycin (3), atomoxetine (3), and lamotrigine (3) the leading agents. Median time from drug initiation to symptom onset was 32 days. Peak (median) liver chemistries were aspartate aminotransferase 503 U/L, alanine aminotransferase 727 U/L, alkaline phosphatase 331 U/L, and total bilirubin 3.9 mg/dL. Autoantibodies were common (64%). Liver injury pattern was hepatocellular 78%, cholestatic 13%, and mixed 9%. The DILI episode was scored: mild 32%, moderate 44%, severe 20%, and fatal (within 6 months) 4%. Causality assessment was definite 36%, very likely 36%, probable 16%, possible 8%, and unlikely 4%. Seven percent had persistent liver test abnormalities at 6-month follow-up suggesting chronic DILI. Liver biopsies from 12 children most frequently demonstrated chronic hepatitis or bile duct injury. Idiosyncratic DILI in children is most commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. The majority of patients recover, but morbidity and infrequent mortality are seen.

Abnormal liver tests in people aged 75 and above: prevalence and association with mortality

Despite their common use the occurrence and consequences of abnormal liver tests remain unclear. To estimate the prevalence and mortality associated with abnormal liver tests in people aged 75 years and above. A cohort study on 13,276 people aged 75 years and above, registered with general practices, with a valid measurement of one or more liver test, calculating the prevalence of abnormal aspartate transaminase (AST), alkaline phosphatase (ALP) or bilirubin. Hazard ratios (HRs) were calculated for all-cause and cause-specific mortality comparing elderly patients with abnormal liver tests to elderly patients with normal liver tests. At least one abnormal liver test was found in 2175 subjects (16.1%, 95% CI [15.4%, 16.7%]). The prevalence of a single abnormal liver test was 3.3% (95% CI [3.0%, 3.7%]) for AST, 9.2% (95% CI [8.8%, 9.7%]) for ALP and 5.4% (95% CI [5.1%, 5.9%]) for bilirubin. Abnormal AST, ALP and bilirubin were associated with increased risks of all-cause mortality; adjusted HRs, 1.27(95% CI [1.09, 1.47]), 1.47(95% CI [1.35, 1.61]) and 1.15(95% CI [1.02, 1.30]), respectively. Abnormal AST and ALP were associated with sevenfold and sixfold increased risk of death from liver disease, respectively. Two or more abnormal liver tests were associated with 2-fold and 17-fold increased risk of death from cancer and liver disease, respectively. Of the causes examined, absolute mortality rates were highest for cardiovascular disease in subjects with and without abnormal liver tests. Abnormal liver tests occur commonly in elderly people and are associated with a modest increase in all-cause mortality. There was a strong association with liver disease; however, the majority of deaths were not due to this cause.

Icodextrin-associated hepatotoxicity.

Sir, Abnormal liver function tests can be observed in peritoneal dialysis (PD) patients. The most common cause of these are viral infections, especially hepatitis B and C [1]. Icodextrin-based PD solutions (Extraneal; Baxter, IL, USA) are increasingly used in this patient population [2]. Several adverse reactions have been reported with icodextrin, mainly skin reactions (upto 15%) [3]. In the full prescription catalogue, it is said that it may lead to liver dysfunction, specifically alkaline phospahatase (ALP) and alanine transaminase (ALT) levels. A 26-year-old male PD patient applied to our Transplant Unit to undergo renal transplantation from his mother. He had been on PD for the last 2 months and was treated with a 13 L of 1.36% glucose-containing PD solution and 2 L of Extraneal exchange. He was also on 80 mg/day furosemide. At the time of first visit, he had exfoliative eruptions on his back. Except for high ALT (295 mg/dL, normal <45) and ALP levels (390 mg/dL, normal 35–140), all other liver function parameters were normal. He did not have a history of liver disease and his liver function tests were normal until 2 months ago. His HbsAg, Anti-Hbs, Anti-Hbc, Anti-CMV IgM, Anti-EBV IgM antigen were negative and Anti-CMV IgG and Anti-EBV IgG were positive. Hepatitis C virus was confirmed to be negative by real-time polymerase chain reaction. Alpha-trypsin, ceruloplasmin and autoimmune marker levels were normal. Liver ultrasonography was normal with normal size, paranchyme and echogenity, gall bladder and bile duct was normal. Since there were no evident infectious, metabolic and toxic findings, the decision was made to perform a liver biopsy. However, the patient refused to undergo liver biopsy. After review of the literature on skin lesions and hepatic dysfunction in dialysis patients, we thought that both these signs (eruption and liver dysfunction) may be related to icodextrin use. As a trial and error approach, it was decided to discontinue icodextrin. On Day 3 of discontinuation, ALT levels decreased from 295 to 133 and on Day 11 to normal levels. Similarly, ALP levels decreased from 390 to 260 on Day 11. His previous ALT levels are depicted in Figure 1. Also, exfoliative eruptions disappeared. This trial and error approach showed that the icodextrin-based PD solution was the cause of liver dysfunction. The patient is now transplanted and his liver enzymes continue to be normal. Fig. 1. Serum ALT levels upon icodextrin use and discontinuation. Liver dysfunction was incidentally diagnosed in this case during his preoperative workup for renal transplantation. After exclusion of metabolic disorders, infectious agents, alcoholism and other causes of liver dysfunction, the focus was directed to prescribed drugs. Review of the literature directed us toward icodextrin-based PD solution while it has been linked to skin lesions in PD patients which was also present in our case. However, no valid data exists regarding liver dysfunction with icodextrin-based PD solution. Our trial and error approach showed that it was indeed related to this. Icodextrin is reported as relatively safer compared to glucose-based PD solutions regarding adverse and side effects. The pathophysiological mechanisms underlying liver dysfunction with icodextrin use is unclear. Drug-induced hepatotoxicity can be due to various mechanisms: disturbances in intracellular ion shifts, bile duct injury, apoptosis, mitochondrial dysfunction and direct liver immune injury [4]. Which one/ones of these is responsible for icodextrin-related damage needs to be clarified. As a conclusion, icodextrin may lead to hepatotoxicity, this may be more common than anticipated and shall be taken into account in the differential diagnosis of liver test abnormality in PD patients.

Adult Polyglucosan Body Disease: A Rare Presentation with Chronic Liver Disease and Ground-Glass Hepatocellular Inclusions

Liver involvement in genetic and metabolic disorders may result in intrahepatic accumulation of specific precursors or byproducts, which have distinctive features on light microscopy. The "polyglucosan disorders" are diseases in which polyglucosan (abnormal glycogen with decreased branching) is formed and deposited in various tissues because of decreased or absent glycogen branching enzyme activity. These disorders include Lafora disease (myoclonus epilepsy) and type IV glycogen storage disease. Polyglucosan deposits in both conditions result in ground-glass hepatocellular inclusions resembling those seen in chronic hepatitis B virus infection. In the present report, we describe a case of the rare, adulthood form of glycogen branching enzyme deficiency, adult polyglucosan body disease (APBD), in which abnormal serum liver tests prompted a liver biopsy. The pathologic findings of periportal ground-glass hepatocellular inclusions, mild chronic portal inflammation, and periportal fibrosis are not well described in APBD, but resemble the chronic changes that have been reported in Lafora disease. The differential diagnosis of ground-glass hepatocytes and the genetic basis of APBD are discussed.

Current hepatitis B screening practices and clinical experience of reactivation in patients undergoing chemotherapy for solid tumors: a nationwide survey of medical oncologists.

Universal screening for chronic hepatitis B virus (HBV) before chemotherapy has been recommended by the Centers for Disease Control. We sought to determine the practice of Australian oncologists with regard to HBV screening in patients with solid tumors (STs) and their clinical experience of HBV reactivation (HBVR). A survey was sent to all consultant members of the Medical Oncology Group of Australia. One hundred eighty-eight responses (63% response rate) were received. We also reviewed the incidence of HBV in patients with STs screened at the Peter MacCallum Cancer Centre (Melbourne, Australia). Fifty-three percent of medical oncologists screen for HBV, but only 19% screen all patients. The most common reasons given for performing screening were anecdotal experience of HBVR (46%) and perceived sufficient evidence for screening of some patient subgroups (42%). Sixty-five percent of those who screened did so only in subgroups, usually selecting patients on the basis of ethnicity (82%). Oncologists who did not screen most commonly cited inadequate evidence for a benefit of screening (72%). Twenty-two percent of oncologists had witnessed one or more HBVR events, representing one event per 45 years of respondents' practice. HBVR events reported (n = 54) consisted of asymptomatic liver test abnormalities only (44%), symptomatic hepatitis (28%), decompensated liver failure (19%), and death (7%). In 206 patients with STs screened for HBV, 1.0% (n = 2) were HBV surface antigen positive, and 14.9% hepatitis B core antibody positive. The majority of Australian medical oncologists have not adopted universal HBV screening before chemotherapy. Further evidence of the benefit and cost effectiveness of universal screening in patients with STs will be required to alter practice.

Pretransplantation Liver Function Impacts on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: A Study of 455 Patients

Liver dysfunction is frequent before allogeneic stem cell transplantation (allo-SCT). However, its characteristics and impact on transplantation outcomes are uncertain, especially in the reduced-intensity conditioning (RIC) setting. We analyzed 455 patients receiving an allo-SCT in 3 Spanish centers. Pretransplantation aspartate aminotransferase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin, and international normalized ratio were analyzed. Pretransplantation liver function test abnormalities were found in 94 (22%) patients. The most frequent cause of pretransplantation liver dysfunction was isolated elevation of GGT/AP (n = 49, 53%). Patients with high bilirubin levels before allo-SCT showed higher 4-year nonrelapse mortality (4y-NRM) (hazard ratio [HR] 2 [95% confidence interval [CI] 1.1-3.8] P = .02) and patients with high GGT levels showed higher 100-day NRM and lower 4-year overall survival (OS) (HR 3.4 [95% CI 1.8-6.7] P < .001, and HR 2 [95% CI 1.4-3], P = .001), respectively. High levels of transaminases did not influence on survival or mortality. In conclusion, hepatic dysfunction before allo-SCT is frequent and has an impact on transplantation outcomes. The best indicator of liver dysfunction still has to be determined.

A 17q12 chromosomal duplication associated with renal disease and esophageal atresia

Chromosomal imbalance of the 17q12 region (which includes the HNF1B transcription factor) has recently emerged as a frequent condition. 17q12 deletion was found in patients with various renal abnormalities, diabetes mellitus (MODY type 5), genital tract or liver test abnormalities, while 17q12 duplication was identified in a subset of patients with autism, mental retardation, epilepsy and/or schizophrenia but no renal disorder. We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome.

Serum concentrations of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and cardiovascular risk factors in adolescents

The risk association between the insulin like growth factor-I (IGF-I) system and cardiovascular risk is inconclusive in adults and under-explored in adolescents. We aimed to investigate the associations between serum concentrations of IGF-I and IGF binding protein-3 (IGFBP-3) and cardiovascular risk factors in adolescents. This was a cross-sectional, population-based, observational study in a school setting with 2102 Hong Kong Chinese adolescents aged 12-19 years. Serum IGF-I and IGFBP-3 concentrations were measured by chemiluminescence immunoassays. Anthropometric indices and traditional cardiovascular risk factors were assessed. After excluding participants with abnormal thyroid and liver test results, 765 boys and 877 girls, mean (±SD) age of 15.3 (±2.0) and 15.7 (±2.0) years, respectively, were included in the analysis. Multivariable regression analyses revealed that both IGF-I and IGFBP-3 concentrations were independently associated with waist circumference, fasting insulin and haemoglobin concentrations in boys (all P < 0.05), systolic blood pressure, serum creatinine, fasting insulin and haemoglobin concentrations in girls (all P < 0.05). In girls, IGF-I was also associated with C-reactive protein concentration (P < 0.001) and IGFBP-3 was associated with fasting triglyceride concentration (P < 0.001). Compared with adolescents with the lowest tertile, the top tertile of both IGF-I and IGFBP-3 concentrations were associated with increased odds of having overweight/obesity, top tertiles of insulin and haemoglobin in both boys and girls (P for trend, all <0.05). The associations between serum IGF-I, IGFBP-3, obesity, cardiovascular risk factors, insulin and haemoglobin suggest that dysregulation of the IGF system may play a linking role for the clustering of cardiovascular risk factors.

New clinical score to diagnose nonalcoholic steatohepatitis in obese patients

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most frequent disease associated with abnormal liver tests that is characterized by a wide spectrum of liver damage, ranging from simple macro vesicular steatosis to steatohepatitis (NASH), cirrhosis or liver carcinoma. Liver biopsy is the most precise test to differentiate NASH from other stages of NAFLD, but it is an invasive and expensive method. This study aimed to create a clinical laboratory score capable of identify individual with NASH in severely obese patients submitted to bariatric surgery.MethodsThe medical records from 66 patients submitted to gastroplasty were reviewed. Their chemistry profile, abdominal ultrasound (US) and liver biopsy done during the surgical procedure were analyzed. Patients were classified into 2 groups according to liver biopsy: Non-NASH group - those patients without NAFLD or with grade I, II or III steatosis; and NASH group - those with steatohepatitis or fibrosis. The t-test was used to compare each variable with normal distribution between NASH and Non-NASH groups. When comparing proportions of categorical variables, we used chi-square or z-test, where appropriate. A p-value < 0.05 was considered statistically significant.Results83% of patients with obesity grades II or III showed NAFLD, and the majority was asymptomatic. Total Cholesterol (TC)≥200 mg/dL, alanine aminotransferase (ALT) ≥30, AST/ALT ratio (AAR)≤ 1, gammaglutaril-transferase (γGT)≥30 U/L and abdominal US, compatible with steatosis, showed association with NASH group. We proposed 2 scores: Complete score (TC, ALT, AAR, γGT and US) and the simplified score, where US was not included. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH (sensitivity 70%, specificity 88.6%, NPV 91.2%, PPV 63. 6%).ConclusionAlterations in TC, ALT, AAR, γGT and US are related to the most risk for NASH. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH. Additionally, negative final scores exclude the presence of an advanced illness. Using this score, the severity of fatty liver infiltration would be predicted without the risks associated with hepatic biopsy.

The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid

To observe the characteristics of primary biliary cirrhosis (PBC) with a suboptimal biochemical response to ursodeoxycholic acid. A total of 38 Chinse PBC patients (5 male patients, 33 female patients, average age 55 years old) with treatment of ursodeoxycholic acid in our hospital from January 1999 to January 2009 were erolled and studied retrospectively. 17 suboptimal biochemical responders mainly presented with liver diseases related symptoms including jaundice (41.1%), fatigue, anorexia (23.5%), edema and abdominal distension (11.7%). 21 good biochemical responders mainly presented with abnormal liver function tests without symptoms. The suboptimal biochemical responders had significantly higher baseline levels of total serum bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, immunoglobulin G and globulin as compared to the good biochemical responsers. There were no differences in gender, age and the dose of UDCA. PBC patients with liver diseases related symptoms, marked abnormal liver tests and characteristics of autoimmune hepatitis may have a suboptimal biochemical response to ursodeoxycholic acid treatment.

The Pharmacological Management of Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy is the most common liver disease occurring in the second half of pregnancy, characterized by pruritus and elevated serum bile acids often coupled to abnormal liver tests. Maternal prognosis is favourable with a complete symptom resolution after delivery, while preterm deliveries, fetal respiratory distress and stillbirths may occur. The goal of the pharmacological treatment of the disease is to improve maternal symptoms and biochemical alterations and, most importantly, to reduce fetal adverse events.The present manuscript will review the current knowledge on the pharmacological treatment of intrahepatic cholestasis of pregnancy.

Sorafenib-induced liver failure: a case report and review of the literature.

In patients with hepatocellular carcinoma characterized by vascular invasion and/or extrahepatic disease, Sorafenib is considered treatment of choice. Although mild liver test abnormalities were reported in less than 1% of the patients in the two large randomized, controlled phase III trials, four cases of severe acute Sorafenib-induced hepatitis have been described. One of these four cases died from liver failure. In this paper, a patient with HCC with lung metastases developed high fever and a severe hepatitis that rapidly evolved into liver coma and death, two weeks after the initiation of Sorafenib. Biochemical parameters pointed to a hepatocellular type of injury. Clinical and biochemical presentations were compatible with a drug-induced hypersensitivity syndrome such as it has mainly been described for aromatic anticonvulsants, sulphonamides, and allopurinol. We hypothesize that an underlying cytochrome P450 dysfunction with the presence of reactive drug metabolites might lead to this potentially fatal Sorafenib-induced severe liver dysfunction.

Prevalence and Etiology of Abnormal Liver Tests in an Adult Population in Jilin, China

Serum biochemical liver tests (LTs) (alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase) and platelet counts are often used to screen for chronic liver disease. We determined the prevalence and etiologies of abnormal LTs in an adult population in Jilin, China. A total of 3791 individuals between the ages of 18 and 79 years were interviewed and then underwent ultrasonography and blood tests. The prevalence of abnormal LTs was 14.77% (560 out of 3791 subjects). The risk factors for abnormal LTs were non-alcoholic fatty liver disease (NAFLD) alone, which accounted for 11.61%, metabolic syndrome alone for 25%, or both for 22.14%. Abnormal LTs were more common in male than in female subjects. The development of abnormal LTs was correlated with older age males, increased daily alcohol intake, poor quality of sleep, smoking, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein. Abnormal LTs in patients with metabolic syndrome and NAFLD were associated with high fasting plasma glucose, triglycerides, body mass index, low density lipoprotein, male, young age, poor sleep quality, smoking, and alcohol intake. However, abnormal LTs in patients with hepatitis B virus were associated with gender and increased age. The results from the current study demonstrated that the prevalence of abnormal LTs is high in the population (14.77%). Metabolic syndrome, NAFLD, and alcohol intake appear to be potentially important causes of the observed abnormal LTs.

Occult hepatitis C virus infection and associated predictive factors: The Pakistan experience

The aim of the present study was to determine the presence of HCV RNA in the liver biopsies of patients with abnormal liver tests but without detectable serum HCV RNA and anti-HCV antibodies in sera. Liver biopsies and whole blood of total 31 patients who were negative for anti-HCV antibodies with elevated liver function tests were received at Division of Molecular Diagnostics, University of the Punjab Pakistan from January 2002 to June 2009 for the detection of HCV RNA. HCV RNA status of the subjects was tested by reverse-transcription PCR and quantified using SmartCycler II real-time PCR. HCV genotyping was carried out in HCV RNA positive samples using molecular genotyping method. HCV RNA was found in liver-biopsy specimens from 23 (74.2%) of the total 31 patients negative for anti-HCV antibodies and undetectable serum HCV RNA. HCV RNA of both negative and positive polarity was found in the livers of 8 (25.8%) patients. Genotyping analysis showed that 65% patients were infected with HCV 3a, 17% with 3b, 13% with 1a and 4% patients were found with untypable genotype. In a multivariate logistic regression model, patients having previous history surgeries, male sex and age above 30 years were significantly associated with the presence of occult HCV infection (p<0.05). In conclusion, patients with elevated liver enzymes and negative HCV antibodies and negative serum RNA may have occult HCV infection and its chance increases with previous history of surgeries, in male sex and above 30 years of age.

High-dose frequency beta-interferons increase the risk of liver test abnormalities in multiple sclerosis: a longitudinal study

Background: Post-marketing studies and case reports have linked beta-interferon (IFNβ) treatment with liver enzyme abnormalities and liver injuries in patients with multiple sclerosis (MS). Few predictors of risk exist. Objective: We investigated the effect of IFNβ and other patient characteristics on levels of the liver enzyme, alanine aminotransferase (ALT). Method: Repeated ALT test results were reviewed retrospectively for 1064 MS patients prescribed an IFNβ as their first immunomodulatory drug. Liver enzyme abnormality was defined as an ALT elevation twice the upper limit of normal (≥2 ULN). The Generalized Estimating Equation (GEE) was used to analyze the effect of age (≤35, >35–40, >40–45, >45 years), gender, disease duration, IFNβ product, and duration of treatment (≤5, >5–15, >15–40, >40 months) on de novo liver enzyme abnormality. Results: Over a mean treatment period of 38.7 months (SD = 34.9), 12.4% (95/766) of MS patients developed de novo liver enzyme abnormality. Multivariable GEE results showed a dose frequency response effect of IFNβs on liver enzyme abnormality: OR = 3.8(95% CI: 1.6–9.2) for IFNβ-1a 44 µg SC, and OR = 3.4 (95% CI: 1.5–7.9) for IFNβ-1b 250 µg SC compared with the lower frequency IFNβ-1a 30 µg IM. Younger age (≤40 years), male gender, and ≤15 months of IFNβ exposure were also independent predictors. Conclusion: A dose frequency response effect was observed, with high-frequency IFNβs having the greatest risk. The first 15 months of treatment, men, and younger patients were also associated with elevated risk. Regular ALT monitoring in MS patients appears prudent; long-term consequences of ALT elevations should be further investigated.

Hépatite lupique : une série de 12 patients

Purpose Several liver manifestations have been reported in systemic lupus erythematosus (SLE) and are usually non specific. We report on our experience of lupus hepatitis. Methods A retrospective monocenter study of 73 patients with SLE. The diagnosis of lupus hepatitis was established after exclusion of other causes of hepatitis and hepatic vein thrombosis. Results Liver involvement was noted in 12 patients (16.4%). There were nine female and three male patients; the mean age of these patients was 29 years. In seven patients liver involvement was concurrent with the diagnosis of SLE and it occurred later during an exacerbation of the disease in the five remaining patients. In all patients, liver manifestations were associated with other organ involvement. Clinical manifestations were: hepatomegaly ( n = 4), jaundice ( n = 4), abdominal pain ( n = 3), ascitis ( n = 2), portal hypertension ( n = 1) and hepatic failure with encephalopathy ( n = 1). Elevated liver enzyme was noted in 11 cases and liver cholestasis in eight cases. Presence of anti-ribosomal P antibodies was noted in one case. Liver biopsy was performed in five patients, and revealed chronic active hepatitis in three cases, chronic hepatic granulomas in one case and nonspecific inflammation in one case. The outcome was favorable in 11 patients without relapse, and one patient died of encephalopathy and liver failure. Conclusion Liver involvement associated with SLE is not uncommon. It is frequently asymptomatic and limited to liver test abnormalities. The role of anti-ribosomal P autoantibodies remains uncertain.

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis

Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. None.