Normal Aminotransferase Levels Research Articles

Genetic risk factors of cytolysis syndrome in the treatment of recrudescence of chronic cardiovascular diseases

Aim . To assess the clinical, biochemical, and genetic risk factors for the development of hepatocyte cytolysis syndrome in patients with a combination of fatty liver disease and recrudescence of chronic cardiovascular pathology. Material and methods . The study included 74 patients with chronic cardiovascular disease (coronary heart disease, chronic heart failure, hypertension) treated in the cardiology department of the Central Clinical Hospital of the Siberian Branch of Russian Academy of Sciences with a normal baseline transaminase level (AST and ALT); 12 of them have increasing of transaminase level on 10-12 days. All patients underwent therapeutic and diagnostic procedures in accordance with the medical standards in Russian Federation. Genotyping of polymorphic loci of the genes of the cytochrome P450 family was carried out using real-time polymerase chain reaction (PCR). Results . There was no significant correlation between cytolysis syndrome and phenotypic characteristics: gender, age, body mass index. A positive correlation of fatty liver disease with abdominal obesity and body mass index was confirmed. There was no significant correlation between cytolysis syndrome and clinical and biochemical risk factors: comorbidity and lipid profile. The presence of minor minor allele of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes in a patient with fatty liver disease increases the risk of cytolysis syndrome during CVD therapy. Conclusion . Pharmacogenetic testing of polymorphic variants of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes is advisable to recommend to patients with cardiovascular diseases and high-risk of liver disorders for a personalized approach to therapy.

Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C.

Interferon-free, direct-acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection. The purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct-acting antiviral treatments in patients with chronic hepatitis C. Among 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct-acting antivirals, 51 underwent liver biopsy 41 ± 20 weeks after the end of treatment despite normal transaminase levels. In 20 patients, liver biopsy specimens obtained a median of 1.2 years before the start of treatment were available. Among the 51 patients who underwent post-sustained virologic response biopsies, the grade of inflammation was A0 in 18 patients, A1 in 24, A2 in eight, and A3 in one; the stage of fibrosis was F0 in three patients, F1 in 20, F2 in 15, F3 in nine, and F4 in four. Among the nine post-sustained virologic response biopsy specimens with moderate-to-severe inflammation (≥A2), four showed S1-to-S3 steatosis (>5% of hepatocytes affected). In the 20 paired biopsy specimens, the inflammation grade significantly regressed (p = 0.0043), but the fibrosis stage did not (p = 0.45). Histological improvement, defined as a ≥ 2-point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found in 11 (55%) patients. The iron accumulation had significantly regressed (p = 0.0093), but the steatosis had not (p = 0.10). Even if transaminases become normal after obtaining a sustained virologic response, significant histological inflammation of unknown cause was found in some patients. Additionally, improvement in liver fibrosis was not evident in the short term.

Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine

BackgroundData on rescue treatment of autoimmune hepatitis in patients that fail standard treatment are sparse. AimsTo report our long-term experience with mycophenolate mofetil. MethodsRetrospective study in 22 patients with autoimmune hepatitis who failed azathioprine and prednisolone due to adverse events (n = 14, 64%), lack of remission (n = 5, 23%) or a combination (n = 3, 13%). ResultsMycophenolate mofetil was started at a dose of 20 mg/kg/day and increased to a maximum of 3 g/day. Follow-up was 0–6 months in 7 patients; more than 12 months in 15 (68%) and more than 24 months in 10. Normal aminotransferase levels were obtained (n = 3) or maintained (n = 7) in 10 patients (45%) after three to 30 weeks. 12 patients (55%) were withdrawn during the first 6 months, due to adverse events. Three patients were switched to cyclosporine and one underwent liver transplantation. Successful treatment with mycophenolate mofetil continued in 10 patients (45%) for a median of 71 months (range 20–124). Of these, one stopped prednisolone, five have a prednisolone dose <5 mg daily and four patients 5–10 mg. ConclusionApproximately one of two patients with autoimmune hepatitis that fail standard treatment benefit from long-term maintenance with mycophenolate mofetil, especially those with previous intolerance to thiopurines, where mycophenolate mofetil is effective in two thirds.

Budd-chiari syndrome due to segmental obstruction of the inferior vena cava successfully managed with endovascular stenting

Budd-Chiari syndrome (BCS), a rare and life-threatening disorder due to hepatic venous outflow obstruction, is occasionally associated with hypoproteinemia. We herein report the first case of BCS with segmental obstruction of the intrahepatic portion of inferior venacava (IVC) and hepatic veins (HVs) successfully treated by endovascular stenting in Vietnam. A 32-year-old female patient presented with a 2-month history of massive ascites and leg swelling. She refused history of oral contraceptives use. Hepatosplenomegaly without tenderness was noted. Laboratory data showed polycythemia, mild hypoalbuminemia and hypoproteinemia, slightly high total bilirubin and normal transaminase level. The serum ascites albumin gradient was 1.9 g/ dL and ascitic protein level was 1.1 g/dL. The other data were normal. BCS was suspected because of the discrepancy between mild liver failure and massive ascites; and the presence of hepatosplenomegaly and polycythemia. On abdominal magnetic resonance imaging, the segmental obstruction of three HVs and IVC was 2-3 cm long without thrombus. Cavogram revealed the severe segmental stenosis of intrahepatic portion of IVC with no visualized HV and extensive collateral veins. A Protégé stent was deployed to IVC. Leg swelling and ascites were completely resolved within 3 days after stenting. During 1-year follow-up, edema was not recurred and repeated laboratory results were all normal.

Assessment of fibrotic burden among chronic hepatitis B virus-infected patients with normal transaminase level

See the Original "Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases" on page 384.

Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment.

ObjectiveThe mechanism of liver injury with low-dose methotrexate (MTX) is incompletely understood. This study was designed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and liver injury during MTX treatment for rheumatoid arthritis (RA).MethodsBetween October 2014 and May 2015, we enrolled all MTX users for RA and monitored participant serum hepatic transaminase levels for 1 year. All patients had normal transaminase levels before the first MTX prescription. Using diagnostic criteria for non-alcoholic steatohepatitis (NASH), we performed histological analyses for patients presenting persistent transaminitis, defined as elevations of hepatic transaminases in four of six determinations during the follow-up period. Possible risk factors for persistent transaminitis were also examined.ResultsWe followed 846 RA patients with a mean cumulative MTX dose of 2.48 g and identified 51 patients presenting persistent transaminitis. According to multivariate logistic regression analysis, obesity (odds ratio [OR] 3.23, p < 0.001), type 2 diabetes (OR 3.52, p = 0.001), hypercholesterolemia (OR 2.56, p = 0.004), and hyperuricemia (OR 3.52, p = 0.019), which are recognized as risk factors for NAFLD, were independently associated with a risk of persistent transaminitis. Among patients with persistent transaminitis, 42 showed fatty liver at ultrasonography. These patients had no evidence of alcoholic fatty liver, chronic viral hepatitis, autoimmune liver diseases, or hereditary liver diseases. Biopsy specimens were obtained from 32 patients, and we found that a NASH-like pattern was the most prevalent histological abnormality. There was no significant impact of MTX dose and duration on the histological severity.ConclusionRisk factors and histological findings are similar between NAFLD/NASH and liver injury during low-dose MTX treatment for RA, which suggests a strong association between both entities. NAFLD/NASH may be an underlying condition causing persistent transaminitis in MTX-treated RA patients. The results of this study illustrate the need for monitoring liver injury in RA patients with NAFLD risk factors during MTX treatment.

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis

BackgroundPatients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.MethodsIn this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.ResultsThe primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group.ConclusionsAmong patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731.)

COMPARATIVE STUDY OF ASCITIC FLUID AND SERUM LEVELS OF CALPROTECTIN, PROCALCITONIN AND ENDOCAN IN PATIENTS WITH LIVER CIRRHOSIS FOR EARLY DIAGNOSIS AND PREDICTION OF SPONTANEOUS BACTERIAL PERITONITIS

Background: Spontaneous bacterial peritonitis (SBP) is a serious, recurrent, and life-threatening condition developing in cirrhotic patients with a high mortality rate. Its diagnosis is based on ascitic fluid polymorphonuclear leukocytes (PMNs) to be more than 250/μL. Objectives: polymorphonuclear leukocytes (PMNs) to be more than 250/μL. Objective: The aim of the study was to evaluate the ascitic fluid and serum levels of calprotectin, procalcitonin (PCT) and endocan as appropriate markers for predicting and diagnosing SBP. Patients and Methods: This study was conducted on 90 patients with liver cirrhosis: 35 with decompensated cirrhosis and spontaneous bacterial peritonitis, 35 with decompensated cirrhosis without spontaneous bacterial peritonitis and 20 with compensated cirrhosis with no ascites. We evaluate the correlations of calprotectin, procalcitonin and endocan with indicators of infection and inflammation associated with spontaneous bacterial peritonitis in liver cirrhotic patients. Ascitic fluid and serum levels of Calprotectin, procalcitonin, endocan, and polymorphonuclear leukocytes, serum CRP, and blood leukocytes were analyzed. The control group (n = 30) composed of healthy blood donors with normal aminotransferase levels, normal complete blood counts and negative markers for viral hepatitis and HIV. Results: Ascitic fluid and serum levels of Calprotectin, procalcitonin, endocan, and PMNs, serum CRP and blood leukocytes were statistically elevated in cirrhotic patients with SBP than the control group and cirrhotic patients without SBP. There were statistically significant correlations between the existence of SBP with serum calprotectin (r = 0.512), serum procalcitonin (r= 0.370), serum endocan (r = 0.501), ascitic calprotectin (r = 508), ascitic procalcitonin (r = 0.501), ascitic endocan (r = 0.496), ascitic PMNs (r = 0.562), and CRP (r = 0.492), for all P < 0.001. The diagnostic accuracies of calprotectin, endocan, procalcitonin, and PMNs were elevated in progressive disease stage. Ascitic PMNs ≥ 250/mm³ had a sensitivity of 97% and specificity of 94.7%, Serum calprotectin levels ≥ 45 µg/ml had a sensitivity of 96% and specificity of 94%, ascitic calprotectin levels ≥ 0.95 µg/ml had a sensitivity of 95% and specificity of 89.2%, serum endocan levels ≥ 2.03 ng/ml had a sensitivity of 90% and specificity of 83.7%, ascitic procalcitonin levels ≥0.33ng/ml had a sensitivity of 89.9% and specificity of 83.3%, ascitic endocan levels ≥ 0.65 ng/ml had a sensitivity of 88.9% and specificity of 78.5%, and lastly serum procalcitonin levels ≥2.50 ng/ml had a sensitivity of 87.9% and specificity of 76.8% for the diagnosis of SBP in decompensated cirrhotic patients. Conclusion: Ascitic fluid PMNs, serum calprotectin, ascitic calprotectin,serum endocan, ascitic procalcitonin, and serum procalcitonin, could be useful as powerful diagnostic markers to assess the progression of liver disease and early prediction of spontaneous bacterial peritonitis in cirrhotic patients.

Diagnostic challenge for the rare lysosomal storage disease: Late infantile GM1 gangliosidosis

BackgroundGM1 gangliosidosis is a rare lysosomal storage disorder caused by GLB1 mutations. Because of its extreme rarity and symptoms that overlap with other neurodegenerative diseases, its diagnosis is sometimes challenging, especially in the late infantile form with less severe phenotype. We aim to expand the clinical and genetic spectrum of late infantile GM1 gangliosidosis. MethodsWe confirmed a diagnosis of GM1 gangliosidosis based on GLB1 mutations and/or the deficiency of β-galactosidase activity. We identified the first two cases by whole-exome sequencing, and then the other six cases by direct sequencing of GLB1 with enzyme analysis. ResultsAll eight patients presented with developmental delay or regression during late infancy and later developed epilepsy, mostly intractable generalized tonic seizures. No clinical signs of storage disorders were noted except for skeletal abnormalities. Interestingly, we found aspartate transaminase (AST) elevations alone with normal alanine transaminase (ALT) levels in all patients. The recurrent mutation, p.D448V in GLB1, accounted for 50.0% of total alleles in our cohort. ConclusionsWith a high index of clinical suspicion, skeletal survey and AST level would be important for early diagnosis of GM1 gangliosidosis. In addition, we would highlight the clinical usefulness of whole-exome sequencing in the diagnosis of non-classical presentation of ultra-rare neurodegenerative disease in children.

Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency.

We describe a novel, two-nanoparticle mRNA delivery system and show that it is highly effective as a means of intracellular enzyme replacement therapy (i-ERT) using a murine model of ornithine transcarbamylase deficiency (OTCD). Our Hybrid mRNA Technology delivery system (HMT) comprises an inert lipid nanoparticle that protects the mRNA from nucleases in the blood as it distributes to the liver and a polymer micelle that targets hepatocytes and triggers endosomal release of mRNA. This results in high-level synthesis of the desired protein specifically in the liver. HMT delivery of human OTC mRNA normalizes plasma ammonia and urinary orotic acid levels, and leads to a prolonged survival benefit in the murine OTCD model. HMT represents a unique, non-viral mRNA delivery method that allows multi-dose, systemic administration for treatment of single-gene inherited metabolic diseases.

Profile of serum transaminases in patients with dengue infection in a tertiary care hospital

Background: Although dengue virus is a non hepatotropic virus, liver injury due to dengue infection is not uncommon. Atypical manifestations with liver involvement have frequently been reported, ranging from mild elevations of aminotransferase levels to fulminant hepatitis. The aim of the present study is to study the serum transaminases level in various forms of dengue infection and correlate with severity.Methods: An analysis of 151 serologically confirmed cases (0-14 yrs) of dengue from June 2017 to July 2017 at a tertiary care hospital, Dharwad was made to assess the frequency and degree of hepatic dysfunction in children with dengue infection by analyzing serum transaminase levels. Patients were classified according to WHO as dengue without warning signs, with warning signs and severe dengue. Patients were divided into primary and secondary dengue based on serology and serum transaminases levels were assessed in each of the above groups. Patients with normal aminotransferase levels were categorized into Grade A, those with atleast one of the enzymes raised to less than 3 times the reference range as Grade B, those with atleast one of the enzymes elevated more than 3 times but less than 10 times as Grade C and those with elevations more than 10 times as Grade D. χ2 test was applied to check statistical significance.Results: During the study period, the total number of serologically confirmed cases of dengue were 151 among which dengue fever without warning signs were 38, with warning signs were 91 and severe dengue were 22. Serum transaminase levels were significantly raised in severe dengue (χ2=14.228, df=6, p=0.027).It was also found that transaminases were significantly higher in secondary dengue infection than primary dengue ( χ2=10.155, df=3, p=0.017). Transaminases were significantly elevated in non-survivors (χ2=16.958, df=3, p&lt;0.001).Conclusions: Hepatic dysfunction was common in all forms of dengue infection, with AST rising significantly more than ALT. Transaminases were significantly elevated in severe dengue and secondary dengue infections. Patients with significantly high transaminases had a poor outcome.

THE EFFICACY OF ERADICATION OF SMALL INTESTINAL BACTERIAL OVERGROWTH IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Background. Emerging evidence suggests a strong interaction between the gut, gut microbiota and liver. Derangement of gut flora, particularly small intestinal bacterial overgrowth (SIBO), occurs in a large percentage of patients with non-alcoholic fatty liver disease (NAFLD) and plays an important role in its pathogenesis. Aim. Study of the frequency of SIBO in various forms of non-alcoholic fatty liver disease, as well as the possibilities of its pathomorphosis as a result of eradication of SIBO as a result of the use of rifaximin or multicomponent probiotic. Material and methods. There were investigated 125 patients with non-alcoholic fatty liver disease (70 men, 55 women aged 18 to 65 years, mean age 37±6.7 years) developed at obesity or type 2 diabetes mellitus, including 85 patients with liver steatosis (group1) and 40 patients with non-alcoholic steatohepatitis (group 2). Patients with concomitant SIBO (70 patients) was treated with rifaximin or multicomponent probiotic. As the main endpoints of the study, the frequency of achieving eradication of SIBO was evaluated (estimated from the results of a repeated H2-lactulose hydrogen test after treatment), as well as a decrease in the severity of liver steatosis by steatometry and a decrease / normalization of transaminase levels 3 months after the start of the treatment. Secondary endpoints included the change in BMI and the HOMA-IR index 3 months after the start of the treatment. Results. SIBO in patients with non-alcoholic fatty liver disease was significantly more frequent than in control (p &lt;0.005), and in patients with non-alcoholic steatohepatitis – significantly more often than in patients with liver steatosis (80 % vs 47.1 %, P &lt;0.01). Eradication of SIBO after use of rifaximin was recorded in 30 of 36 patients with non-alcoholic fatty liver disease (83.3 %), including 16 of 20 patients with steatosis (80 %) and 14 of 16 (87.5 %) patients with non-alcoholic steatohepatitis. In the group of patients taking multicomponent probiotics after treatment, eradication of SIBO was noted in 12 of 36 patients (33.3 %), including 7 patients with steatosis (35 %) and 5 patients (31.3 %) with non-alcoholic steatohepatitis Conclusion. The investigation shows that the eradication of small intestinal bacterial overgrowth has the positive influence on the natural course of NAFLD and use of rifaximine should be discussed as a perspective therapeutic strategy at this pathology

Clinico-pathological Correlation with Liver Enzymes in Dengue Infection

Dengue infection is a major vector borne disease. The classical signs and symptoms include high fever, severe headache, chill, and rash. Atypical manifestations of dengue infection with hepatic involvement are frequently reported, ranging from mild elevations of liver enzymes to acute liver failure. Analysis of 110 serologically confirmed cases of dengue infection in Holy Family Red Crescent Medical College hospital a tertiary care hospital was done. Patients with normal aminotransferase levels were categorized into Grade A, patients with at least one of the enzymes raised above normal but less than 3 times were categorized into Grade B, those with at least one of the enzymes elevated more than 3 times but less than 10 times were graded as C, and those with elevations more than 10 times as Grade D. 83.7% patients had alterations of transaminase levels, with 45.5% categorized into grade b, 30.9% into grade C, and 7.3% into grade D or acute hepatitis (P value 0.224). Rise of aspartate aminotransferase (AS7) levels were higher compared to the levels of alanine aminotransferase (AL7). Liver damage with alteration of aminotransferases is a common manifestation of dengue infection and also valuable markers for monitoring these patients.

Can Fibroscan Replace Liver Biopsy in Assessing Treatment Response in Chronic Hepatitis B? A Comparative Analysis of Staging of Fibrosis by the Two Methods in Rural Tertiary Care Centre

Background and Aim: The treatment of chronic hepatitis B is always challenging. Treatment response varies among individual depending on viral load, drug resistance etc. Hence staging system is necessary during course of therapy. Methods: 20 patients with chronic hepatitis B on treatment were chosen and staging was done with liver biopsy and fibroscan. Staging was done after 3 months of antiviral therapy. Age, sex, liver function tests, USG imaging, UGI Scopy for assessment of varices, coagulation profile and viral load and HBeAg status were done. Results: Out of 20 patients, 15 patients were male and 5 patients were female. 13 in age group 21–30, 5 in 31–40 and 2 in less than 20. 3 patients were in decompensated state as evidenced by oesophageal varices. Patients with ascites were excluded in the study since transcutaneous liver biopsy could not be done in them. Liver function test showed more than 2-fold elevation in transaminase level in 18 patients and 2 patients had normal transaminase level. Prothrombin time/INR found to be normal in 18 patients and only 4 patients had >1.5. Liver biopsy and fibroscan were done simultaneously for all the 20 patients after 3 months of antiviral therapy. Ishak fibrosis score in liver biopsy specimen is compared with fibroscan scoring based on k pascal. Ishak scoring of 1/6 correlates with fibroscan scoring of < 7 kPa in 9 patients. Ishak scoring of 3/6 correlates with fibroscan scoring 7–12 kPa in 5 patients. Ishak score in 6 patients does not correlate with fibroscan score. Conclusion: The duration of treatment and assessing treatment response is made easy through staging system. Though liver biopsy is gold standard in staging the fibrosis, recent noninvasive methods like fibroscan could help in staging fibrosis and hence can help in deciding the therapy. The authors have none to declare.

Wisteria floribunda agglutinin positive Mac-2-binding protein level increases in patients with acute liver injury.

Wisteria floribunda agglutinin positive human Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker for liver fibrosis. However, it is not known whether or not M2BPGi reflects only liver fibrosis. We measured serum M2BPGi levels in patients with acute liver injury. Fifty-one patients with acute liver injury were enrolled. M2BPGi levels were measured at the initial visit and at achievement of recovery. The relationship between M2BPGi values at the initial visit and clinical outcomes was analyzed. Serum M2BPGi levels at the initial visit were elevated in 47 of 51 acute liver injury patients (8.33±7.56 cutoff index). M2BPGi values were associated with prothrombin activity (r=-0.600, P=0.001), total bilirubin level (r=0.588, P=0.001), and Model for End-Stage Liver Disease score (r=0.490, P=0.001) but not with aspartate aminotransferase (r=-0.070) and alanine aminotransferase (r=-0.073) levels. M2BPGi values at the initial visit were significantly higher in patients with acute liver failure (diagnosed by prothrombin activity of 40% or less; P<0.001), subsequent development of hepatic coma (P=0.036), and subsequent requirement of liver transplant (P=0.014), and in a patient who died (P=0.045). M2BPGi values decreased after aminotransferase level normalization in patients who recovered from acute liver injury; however, M2BPGi level was not a predictive factor for recovery with medical therapy. Serum M2BPGi values increased in patients with acute liver injury and decreased following recovery. The marker seems to reflect not only liver fibrosis but also other factors, such as liver inflammation, liver damage, and hepatocyte regeneration.

Serum markers for mitochondrial dysfunction and cell death are possible predictive indicators for drug-induced liver injury by direct acting antivirals.

We prospectively screened patients treated with direct-acting antivirals (DAA) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). The levels of various serum markers among DILI, non-DILI and control groups were compared. The DILI group consisted of eight patients whose alanine aminotransferase (ALT) levels exceeded 32IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, sex and disease severity. Additionally, eight healthy volunteers were employed as the controls. Serum measurements of cytokines/chemokines, cytokeratin-18 fragment (CK-18F) and super oxidase dismutase-2 (SOD2) were evaluated on the date at which hepatitis C virus RNA was absent (baseline). For patients with DILI, serum measurements taken before treatment, 1week before pronounced transaminase elevation (prominence-1W) and on the date at which pronounced elevation of transaminase occurred (prominence) were also evaluated. All patients treated with DAA had normalized transaminase levels at baseline. In patients with DILI, interferon-inducible protein-10 (IP-10) levels were higher at prominence-1W than at baseline. Those patients also had significantly higher levels of SOD2 and CK-18F at prominence-1W than at baseline. Elevated IP-10 may be a preconditioning chemokine for DAA-induced liver injury, and damage markers associated with cell death and mitochondrial dysfunction are potential predictive serum markers for DILI.

Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis

Many patients with autoimmune hepatitis (AIH) develop steroid-specific side effects or require doses of steroids that are unacceptable for long-term treatment. We investigated the efficacy of budesonide as an alternative steroid for patients previously treated with prednisolone who developed side effects or were unable to reduce their dose of prednisolone below acceptable levels. We also report the effects of more than 12 months of budesonide treatment in a large cohort of patients with AIH. We performed a retrospective analysis of data from 60 patients (51 female) with AIH who were treated initially with prednisolone (mean time, 47 mo) but then switched to budesonide, managed at a single center in Germany from 2001 through June 2016. Patients were evaluated after 6 months, 12 months, 24 months, 36 months, and at the last follow-up evaluation; response to treatment with budesonide was assessed based on normal serum levels of aminotransferases and IgG (biochemical response). Thirty patients were switched to budesonide therapy because of prednisolone-induced side effects and 30 patients switched because of prednisolone dependency. Overall, a biochemical response was detected in 55% of patients after 6 months of budesonide treatment, in 70% after 12 months, and in 67% after 24 months. At the last follow-up evaluation (mean time, 63 mo) 23patients (38%) still were receiving budesonide treatment. Fifteen patients (25%) had switched back to prednisolone therapy because of insufficient response to budesonide or its side effects. Fifteen patients with osteopenia at the beginning of budesonide treatment were followed up and evaluated by dual-energy X-ray absorptiometry. After a median of 24 months of budesonide treatment, bone mineral density had improved in 6 patients, remained stable in 8 patients, and worsened in 1 patient. We performed a retrospective analysis of patients with AIH that confirmed the therapeutic value of budesonide beyond 12 months of treatment in patients who are intolerant to or dependent on prednisolone. Although budesonide-induced side effects appear to be mild in real life, effectiveness was limited in a considerable proportion of patients; close monitoring is advised.

Factors Predicting HBsAg Seroclearance and Alanine Transaminase Elevation in HBeAg-Negative Hepatitis B Virus-Infected Patients with Persistently Normal Liver Function.

BackgroundA certain proportion of hepatitis B virus (HBV)-infected patients with persistently normal alanine transaminase (ALT) levels have significant fibrosis. Using liver stiffness measurements (Fibroscan®) and laboratory data, including serum ALT, quantitative HBsAg (qHBsAg), and HBV DNA, we attempted to predict the natural histories of these patients.MethodsNon-cirrhotic HBeAg-negative chronic hepatitis B patients with persistently normal ALT were followed up prospectively with the end points of HBsAg seroclearance and ALT elevation above the upper limit of normal. The factors that were predictive of the end points were identified.ResultsA total of 235 patients with an average age of 48.1 +/- 10.7 years were followed up for 7 years. Eight patients (3.4%) lost HBsAg, and 15 patients (6.4%) experienced ALT elevation. The overall cumulative HBsAg seroclearances were 0.4%, 1.3% and 2.3% at years 1, 3 and 5, respectively. Regarding HBsAg seroclearance, the qHBsAg (< 30 IU/ml) cutoff resulted in a hazard ratio (HR) of 19.6 with a 95% confidence interval (CI) of 2.2–166.7 (P = 0.008). The baseline ALT level (odd ratio (OR) 1.075, 95% CI 1.020–1.132, P = 0.006) and a qHBsAg above 1000 IU/ml (3.7, 1.1–12.4, P = 0.032) were associated with ALT elevation. Limited to men, the baseline liver stiffness (1.6, 1.0–2.5, P = 0.031) and a qHBsAg above 1000 IU/ml (10.4, 2.1–52.4, P = 0.004) were factors that were independently associated with ALT elevation.ConclusionA low qHBsAg level predicted HBsAg clearance. Baseline ALT and a qHBsAg above 1000 IU/ml were independent predictive factors for ALT elevation. Among the men, the independent predictive factors for ALT elevation were qHBsAg and liver stiffness.

Clinicopathological features of choledocholithiasis patients with high aminotransferase levels without cholangitis

Common bile duct (CBD) stones are generally associated with greater elevations of alkaline phosphatase and gamma-glutamyl transpeptidase levels than aspartate aminotransferase and alanine aminotransferase levels. However, some patients with CBD stones show markedly increased aminotransferase levels, sometimes leading to the misdiagnosis of liver disease. Therefore, the aim of this study was to investigate the clinicopathologic features of patients with CBD stones and high aminotransferase levels.This prospective cohort study included 882 patients diagnosed with CBD stones using endoscopic retrograde cholangiopancreatography (ERCP). Among these patients, 38 (4.3%) exhibited aminotransferase levels above 400 IU/L without cholangitis (gallstone hepatitis [GSH] group), and 116 (13.2%) exhibited normal aminotransferase levels (control group). We compared groups in terms of clinical features, laboratory test results, radiologic images, and ERCP findings such as CBD diameter, CBD stone diameter and number, and periampullary diverticulum. Liver biopsy was performed for patients in the GSH group.GSH patients were younger and more likely to have gallbladder stones than control patients, implying a higher incidence of gallbladder stone migration. Also, GSH patients experienced more severe, short-lasting abdominal pain. ERCP showed narrower CBDs in GSH patients than in control patients. Histological analysis of liver tissue from GSH patients showed no abnormalities except for mild inflammation.Compared with control patients, GSH patients were younger and showed more severe, short-lasting abdominal pain, which could be due to a sudden increase of CBD pressure resulting from the migration of gallstones through narrower CBDs. These clinical features could be helpful not only for the differential diagnosis of liver disease but also for investigating the underlying mechanisms of liver damage in obstructive jaundice. Moreover, we propose a new definition of “gallstone hepatitis” based on the specific clinicopathologic characteristics observed in our patients.

The overall computer/mobile devices usage time is related to newly diagnosed non-alcoholic fatty liver disease: a population-based study

Background: The computer/mobile devices usage time (CMD-UT) is closely related to a sedentary lifestyle, which is an important risk factor for non-alcoholic fatty liver disease (NAFLD). But their direct relationship remains unclear.Aims: We aimed to examine the relationship between CMD-UT and newly diagnosed non-alcoholic fatty liver disease (NAFLD) in Chinese adults.Methods: This cross-sectional study was conducted on 7516 adults in Tianjin, China. The CMD-UT was collected via a questionnaire included five categories. NAFLD [with normal or elevated alanine transaminase (ALT) levels] was diagnosed by at least twice liver ultrasonography examinations and serum ALT concentrations (>41 U/L in males and >33 U/L in females).Results: The prevalence of overall NAFLD, NAFLD with normal or elevated ALT levels was 18.2, 14.2, and 4.0%, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having overall NAFLD by increasing CMD-UT levels were 1.00 for <1 h/d, 1.58 (1.22–2.05) for 1-3 h/d, 1.58 (1.18-2.11) for 3–5 h/d, 1.65 (1.21-2.27) for 5–10 h/d, and 1.99 (1.29-3.05) for ≥10h/d (P-trend for CMD-UT levels = 0.02), respectively. Similar relations were observed with the use of NAFLD with normal or elevated ALT levels.Conclusions: The present study is the first to find that CMD-UT levels are independently associated with NAFLD.Key MessagesThe computer/mobile devices usage time levels are independently associated with the prevalence of non-alcoholic fatty liver disease.