Aspartate Aminotransferase/alanine Aminotransferase Research Articles

A Unique Case of Autoimmune Hepatitis Developing in a Patient with Kikuchi-Fujimotoʼs Disease

Purpose: We describe a 35 year old Hispanic woman with Kikuchi-Fujimoto's disease (KFD) who developed jaundice; abnormal liver function tests (LFTs) and was found to have developed autoimmune hepatitis (AIH). KFD (histiocytic necrotizing lymphadenitis) is a rare condition of unknown etiology first described in 1972 independently by Kikuchi and Fujimoto. It is a nonmalignant disease characterized by fever and cervical adenopathy and has a self-limiting course. This is the first reported case of a patient with histologically confirmed KFD developing AIH. One prior case report has described KFD occurring after AIH. A 35 year old Hispanic female was referred to our hepatology clinic due to complaints of worsening fatigue and jaundice for two weeks. Her past medical history was significant for KFD diagnosed 14 months ago via cervical lymph node biopsy. She was not on any treatment. On examination, the patient's vital signs were stable and she was afebrile. Abdominal examination was significant for mild tenderness in the right upper quadrant without any guarding or rigidity. Pertinent abnormal laboratory data included Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) 1122/1247 U/L, Alakaline phosphatase 213 U/L, Gammaglutamyl transferase 216 U/L, total bilirubin 5.7 mg/dl, conjugated bilirubin 3.6 mg/dl, total protein 8.5 g/dl, albumin 3.3 g/dl, elevated Immunoglobulin G (IgG) level 2450 mg/dl and anti-smooth muscle antibody positive 1:640. The complete blood count, serum chemistry, viral hepatitis serologies, iron panel, ferritin, ceruloplasmin, alpha one antitrypsin, anti-nuclear antibody, anti-mitochondrial antibody and tissue-transglutaminase antibody were normal. Liver ultrasound was suggestive of mild diffuse fatty infiltration. A liver biopsy was performed which showed lymphoplasmacytic infiltrates, interface hepatitis, grade 4/4 inflammation, stage 2/4 fibrosis. The patient was diagnosed with AIH based on the clinical presentation, laboratory data and the biopsy results. The pre-treatment AIH score was 18. The patient was started on prednisone 60 mg orally daily for one week and there was significant improvement in LFTs. The steroid dose was tapered in the following weeks and the patient was noted to have complete normalization of LFTs and IgG by the fifth week of therapy. Azathioprine 75 mg daily was added with the tapering of the prednisone dose. Six months post-diagnosis, the patient is asymptomatic on a maintenance dose of prednisone 5 mg and azathioprine 75 mg daily. The coexistence of KFD and AIH is extremely rare in the reported literature. Our case is unique as it is the first reported case of histologically confirmed KFD who developed jaundice and was subsequently found to have AIH.

A Unique Case of Acute Hepatitis Developing after Fo-Ti Root Ingestion

Purpose: The use of dietary and herbal supplements by adults in the United States increased from 23 million to over 38 million users between 1997 and 2002. Although herbal products are thought to be safe by many people, they may have biological activity that can lead to “therapeutic misadventures”. We describe one such case. A 26 year old woman from the Philippines presented with two days of non-bloody, non-bilious vomiting and abdominal pain that started after an alcoholic binge. She denied having any medical problems, prior heavy alcohol use, or any similar episodes in the past. She had been taking an over the counter (OTC) beauty supplement “RejuviCare™ - hair and nail formula” the contents of which included Fo-Ti root (Polygonum multiflorum) for the past three months. She denied any illicit drug use. On examination, the patient's vital signs were stable and she was afebrile. Abdominal examination was significant for mild right upper quadrant tenderness without any guarding or rigidity. Pertinent laboratory data included Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) 3357/2887 U/L, Alkaline phosphatase 56 U/L, Gamma-glutamyl transferase 72 U/L, total bilirubin 1.3 mg/dl, conjugated bilirubin 0.5 mg/dl, albumin 4.5 g/dl. The complete blood count, serum chemistry, coagulation profile, viral hepatitis serologies, iron panel, ferritin, ceruloplasmin, alpha one antitrypsin, anti nuclear antibody, and tissue transglutaminase antibody were normal. Anti smooth muscle antibody and anti mitochondrial antibody were mildly elevated with titers of 1:40 and 1:20 respectively. Liver ultrasound was normal. A liver biopsy revealed scattered foci of lobular necroinflammation, aggregates of ceroid containing macrophages, no evidence of chronic liver injury, grade 2/4 inflammation, and stage 0/4 fibrosis. These findings were consistent with acute toxic liver injury. The herbal medication was discontinued and serial liver function tests showed gradual improvement and complete normalization after three weeks. Liver toxicity with the use of herbal medication containing Fo Ti root is rare in the reported literature. Fo Ti root has been thought to contain an alkaloid that may have rejuvenating effects on brain cells, nerves and endocrine glands. The side effects of this remedy are unknown and are considered safe for use by many people. There have been two other cases reporting a cholestatic hepatitis with the use of Fo Ti root. Our case is unique in that it is the first reported case with a hepatocellular hepatitis and normal bilirubin. This case points to the importance of a detailed history in assessing patients with acute hepatitis as patients often fail to mention the use of OTC medications.

F-18 FDG PET Images for Subcutaneous Panniculitis-like T-Cell Lymphoma

A 14-year-old girl, who had been suffering from intermittent fevers for 2 months, developed painful erythematous plaques on the lower extremities. Laboratory data revealed elevated C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase/alanine aminotransferase (AST/ALT). Blood and urine cultures were negative. CT showed hepatosplenomegaly. F-18 FDG PET revealed multiple patchy uptakes on the subcutaneous surfaces residing mainly at the lower trunk and extremities. The PET images and clinical manifestations appeared indistinguishable from those due to panniculitis while the pathology from skin biopsy demonstrated panniculitis-like T-cell lymphoma. She received chemotherapy and the follow-up PET showed significant resolution of previous abnormal uptakes from the subcutaneous lesions.

Dietary Diacetylene Falcarindiol Induces Phase 2 Drug-Metabolizing Enzymes and Blocks Carbon Tetrachloride-Induced Hepatotoxicity in Mice through Suppression of Lipid Peroxidation

Falcarindiol is a diacetylenic natural product containing unique carbon-carbon triple bonds. Mice were orally administrated falcarindiol (100 mg/kg), and drug-metabolizing and antioxidant enzymes were monitored in several tissues of mice. Treatment with falcarindiol was found to increase glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 activities in liver, small intestine, kidney, and lung. No changes were observed in cytochrome P450 (CYP) 1A known to activate procarcinogens. Western blot analysis revealed that various GST subunits including GSTA4, which plays an important role in the detoxification of alkenals produced from lipid peroxides, were induced in liver, small intestine, and kidney of falcarindiol-treated mice. Additionally, we investigated the protective effects of falcarindiol against hepatotoxicity induced by carbon tetrachloride (CCl(4)) and the mechanism of its hepatoprotective effect. Pretreatment with falcarindiol prior to the administration of CCl(4) significantly suppressed both an increase in serum alanine transaminase/aspartate transaminase (ALT/AST) activity and an increase in hepatic thiobarbituric acid reactive substance levels without affecting CCl(4)-mediated degradation of CYP2E1. Formation of hexanoyl-lysine and 4-hydroxy-2(E)-nonenal-histidine adducts, lipid peroxidation biomarkers, in homogenates from the liver of CCl(4)-treated mice was decreased in the group of mice pretreated with falcarindiol. These results suggest that the protective effects of falcarindiol against CCl(4) toxicity might, in part, be explained by anti-lipid peroxidation activity associated with the induction of the GSTs including GSTA4.

Radiofrequency ablation of hepatocellular carcinoma extended into the portal vein: Preliminary results

Introduction We report our preliminary results of radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and neoplastic portal thrombus (NPT) in cirrhotic patients. Methods Ten patients (7 males and 3 females; mean age 68 yrs) with 10 HCC nodules (37–49 mm) extended into the main portal vein (MPV) underwent RF ablation. Diagnosis of NPT was achieved by fine-needle biopsy. RF ablation was performed firstly on the NPT and then on the HCC. RF ablation was considered successful when complete necrosis of the HCC and complete recanalization of the MPV were achieved. HCC necrosis was evaluated using contrast-enhanced CT. Recanalization of the portal vessels (PV) was analyzed using Color Doppler (CD). RF ablation was performed under ultrasonographic (US) guidance using a perfused electrode needle. Results Complete necrosis of the HCC with complete recanalization of the PV was observed in 7 patients (success rate: 70%). In the remaining 3, necrosis of the HCC ranged from 70% to 95%, and recanalization of the PV was not complete. No major complications occurred. In 2 cases, mild ascites and increased aspartate aminotransferase/alanine aminotransferase (AST/ALT) values were observed. The follow-up ranged from 4 to 24 months; 1 and 2-year survival rates were 77% and 77%, respectively. At the last follow-up, the 7 successful patients were alive and the portal system was still patent. The 3 unsuccessful patients died within 5 months due to progressive disease. Conclusion RF ablation can destroy HCC and NPT achieving a high rate of efficacy and low rate of complications. However, to confirm these results a control group and a longer follow-up are required.

The diagnostic value of combining carbohydrate-deficient transferrin, fibrosis, and steatosis biomarkers for the prediction of excessive alcohol consumption

The validity of biomarkers of excessive alcohol drinking (EAD) (30 g/day or more), such as carbohydrate-deficient transferrin (CDT%), is confounded by liver disease severity. The aim was to improve the accuracy of the percentage of CDT by taking into account the presence of fibrosis and steatosis, estimated using biomarkers FibroTest and SteatoTest. Three hundred and twenty consecutive patients, 97 with alcoholic liver disease (ALD), and 223 non-ALD, were included. In ALD, 58% had advanced fibrosis and 58% had steatosis; in non-ALD, 25% had advanced fibrosis and 25% had steatosis. The mean percentage of CDT was lower in ALD with advanced fibrosis [2.4 (SE=0.2)] versus without [4.1 (0.3) P<0.0001], and lower in ALD with steatosis versus without (2.4 vs. 3.9; P=0.0007). Among non-ALD, there was no difference in the percentage of CDT according to fibrosis or steatosis. gamma-glutamyl-transpeptidase was higher in patients with advanced fibrosis or with steatosis both in ALD and non-ALD. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) was higher in ALD patients with fibrosis versus without (2.5 vs. 1.3 P<0.0001) but not in non-ALD (1.01 vs. 0.98). AST/ALT was higher in ALD patients with steatosis versus without (2.2 vs. 1.6 P=0.04) and the inverse was observed in non-ALD (0.6 vs. 1.1 P<0.0001). In the entire population the percentage of CDT, gamma-glutamyl-transpeptidase, AST/ALT was associated with EAD, the area under the receiver operating characteristic curve =0.89 (95% CI: 0.84-0.93), 0.93 (0.89-0.93) and 0.77 (0.71-0.82). An algorithm combining the percentage of CDT, FibroTest and SteatoTest permitted to obtain area under the receiver operating characteristic curve=0.92 versus 0.88 for the percentage of CDT (P=0.004) with 87.4% of patients classified correctly. Biomarkers of EAD are confounded by fibrosis and steatosis. Accuracy of the percentage of CDT is significantly increased when combined with biomarkers of fibrosis and steatosis.

Outcomes of Schistosoma mansoni infection in outbred albino mice exposed to Larvin contaminant

The present study tested the hypothesis that mice exposed to Schistosoma mansoni and treated with the insecticide Larvin have an increased risk of accelerated liver damage. To investigate this hypothesis, adverse effects resulting from treatment with Larvin were compared between S. mansoni-exposed and nonexposed outbred albino mice. The effects of concurrent treatment with Larvin on the progress and outcomes of S. mansoni infection were assessed via macroscopic and microscopic examination of liver and spleen, evaluation of several hematological, biochemical and hepatic enzymes parameters, and effect on worm burden. Oral administration of 1/5 and 1/10 LD(50) of Larvin to S. mansoni-exposed mice induced (1) hepatomegaly and splenomegaly; (2) prominent lymphocytic aggregation in liver replacing large areas of bridging necrosis; (3) increased serum level of bilirubin and alanine aminotransferase-aspartate aminotransferase enzymes; (4) decreased serum level of albumin and total proteins; and (5) decreased RBC, hemoglobin content, leukocyte, and lymphocyte counts. No significant effect on worm burden or oviposition was noted as a result of Larvin treatment compared to controls. All doses used in mice either for infection with S. mansoni cercariae or treatment with Larvin resulted in dose dependent alterations in hepatic functions of the tested mice. These alterations were most profound in mice exposed to S. mansoni and receiving Larvin treatment. The present findings support our hypothesis and show that concurrent S. mansoni infection with exposure to Larvin adversely affect liver functions and seriously alter hematological, biochemical, and hepatic enzymes parameters in outbred albino mice. These findings warrant further investigation and reinforce the need to minimize exposure to insecticide in both natural field settings and the broader environment.

High incidence of adverse events in healthy volunteers receiving rifampicin and adjusted doses of lopinavir/ritonavir tablets

Previous research in healthy volunteers has demonstrated that rifampicin and adjusted doses of lopinavir/ritonavir soft-gel capsules resulted in adequate exposure to lopinavir. Our objective was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets. A total of 40 healthy volunteers were planned to start with 600 mg rifampicin once daily from days 1-5. From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily. A 12 h pharmacokinetic curve was planned on day 15. Safety assessments were conducted regularly throughout the study period. Eleven volunteers started as the first group in this study. No major complaints occurred during day 1-5 (rifampicin only). After addition of lopinavir/ritonavir, eight volunteers suffered from both nausea and vomiting, one from nausea only, and one from vomiting only. On day 7, increases in aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were reported in all volunteers and on day 8, the study was prematurely terminated. The AST/ALT levels continued to rise and peaked (grade 2, n = 2; grade 3, n = 1; grade 4, n = 8) on days 9-10. All values returned to normal within 6 weeks. The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin. In the future, this drug combination should not be given to healthy volunteers. Liver function should be carefully monitored when rifampicin and lopinavir/ritonavir are combined in patients.

Risk factors associated with nonalcoholic fatty liver disease and its relationship with the hepatic histological changes

The objective of this study is to determine the association between risk factors and nonalcoholic fatty liver disease (NAFLD), and to establish the relationship between risk factors and hepatic histological changes in obese women. A case-control design study. Women with NAFLD (cases) were compared with a control group of obese women without NAFLD matched by age, body mass index, waist circumference, and body fat. Irrespective of serum aminotransferases levels, diagnosis of NAFLD was established by the presence of type II diabetes, hypertriglyceridemia, and ultrasonographic changes of hepatic steatosis. Diagnosis of nonalcoholic steatohepatitis was performed by a liver biopsy. Women with an aspartate aminotransferase/alanine aminotransferase (ALT) ratio of at least 1 underwent liver biopsy. Alcohol consumption, hepatitis, and drugs that promote cholestasis or liver injury were the exclusion criteria. Multiple regression analysis was used to compute the association between the risk factors and NAFLD, and Spearman's analysis was used to examine its relationship with histological hepatic changes. A total of 108 obese women were enrolled. The frequency of high blood pressure, hypertriglyceridemia, and diabetes was similar between the groups. ALT (54.4+/-33.3 and 39.8+/-29.8, P=0.03) but not aspartate aminotransferase (45.4+/-23.1 and 36.7+/-21.2, P=0.06) was significantly higher in the women with NAFLD. The multivariate regression analysis showed a significant association of ALT (odds ratio 2.7; 95% confidence interval, 1.3-10.4), but not other variables with NAFLD. Type II diabetes was strongly correlated with ballooning and inflammation, and ALT with inflammation and fibrosis. Obese women with similar metabolic alterations exhibit different hepatic outcomes. Elevation of ALT, but not other risk factors, was associated with NAFLD. Diabetes and ALT correlate with histological hepatic changes.

ASAT/ALAT ratio provides prognostic information independently of Child-Pugh class, gender and age in non-alcoholic cirrhosis

Objective. The aspartate amino transferase/alanine amino transferase (ASAT/ALAT) ratio is increased in cirrhosis. Some studies indicate that the ratio may provide prognostic information as well. The purpose of this study was to further elucidate the role of the ASAT/ALAT ratio as a predictor of survival by assessing it together with classical risk factors such as age, gender and Child-Pugh (CP) class in a mixed cohort of patients with cirrhosis. Material and methods. Eighty-nine patients with alcoholic cirrhosis and 81 patients with non-alcoholic cirrhosis treated at Aker University Hospital between 1999 and 2004 were identified retrospectively. Survival data from these patients per August 2006 were retrieved from the Norwegian Death Registry. Clinical and biochemical data at time of diagnosis were assessed as predictors of survival using the Kaplan-Meier method and Cox regression models. Results. Median ASAT/ALAT ratio was significantly higher in alcoholic cirrhosis (2.42) as compared with non-alcoholic cirrhosis (1.42). In both groups, a ratio above the median was predictive of poor outcome, p=0.024 and p=0.032, respectively. Other significant predictors of death were CP class (p<0.001), clinical decompensation (p<0.001) and age (p=0.001). Cox regression analyses showed that the ASAT/ALAT ratio was a predictor of death independently of CP class, gender and age in non-alcoholic, but not in alcoholic cirrhosis. The estimated increased hazard (risk of dying) in non-alcoholic cirrhosis was 5% (CI: 1–8%) per 0.10 increase in ASAT/ALAT ratio. Conclusions. A high ASAT/ALAT ratio is associated with increased mortality in cirrhosis. In non-alcoholic patients the ratio may provide prognostic information independently of classical risk factors.

Noninvasive Assessment of Liver Fibrosis and Portal Hypertension With Transient Elastography

Hepatic fibrogenesis, the "final" common result of injury to the liver, is believed to be a critical factor leading to hepatic dysfunction and may be important in the pathogenesis of portal hypertension. Thus, accurate assessment of the degree of fibrosis is important clinically. For many years, examination of hepatic histopathology has been considered to be the "gold standard" tool used to assess fibrosis. However, liver biopsy is invasive, and in many instances not favored by patients or physicians. Thus, alternative approaches to measure liver fibrosis would be extremely attractive. To the extent that transient elastography is able to measure "liver stiffness," which is proportional to the degree of liver fibrosis, this technique holds great promise.

Validation of three noninvasive laboratory variables to predict significant fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia

BACKGROUNDWe tested the clinical utility of the platelet count, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the AST to platelet ratio index (APRI) score in predicting the presence or absence of advanced fibrosis and cirrhosis in patients with chronic hepatitis C in Saudi Arabia.METHODSLiver biopsy procedures performed on chronic hepatitis C patients in our gastroenterology unit at King Khalid University Hospital were traced from records between the years 1998 to 2003. The hospital computer database was then accessed and detailed laboratory parameters obtained. By plotting receiver operating characteristic curves (ROC), three selected models (platelet count, AST/ALT ratio, and the APRI score) were compared in terms of the best variable to predict significant fibrosis.RESULTSTwo hundred and forty-six patients with hepatitis C were included in this analysis. Overall, 26% of patients had advanced fibrosis. When comparing the three above-mentioned prediction models, the APRI score was the one associated with the highest area under the curve (AUC) = 0.812 (95% CI, 0.756–0.868) on the ROC curves, compared to the platelet count and AST/ALT ratio, which yielded an AUC of 0.783 (0.711–0.855) and 0.716 (0.642–0.789), respectively.CONCLUSIONThe APRI score seemed to be the best predictive variable for the presence or absence of advanced fibrosis in Saudi hepatitis C patients.

Protective effects of medical ozone combined with traditional Chinese medicine against chemically-induced hepatic injury in dogs

To investigate the protective effect of medical ozone (O(3)) combined with Traditional Chinese Medicine (TCM) Yigan Fuzheng Paidu Capsules (YC) against carbon tetrachloride (CCl(4))-induced hepatic injury in dogs. Thirty healthy dogs were divided randomly into five groups (n = 6 in each group), namely control, oleanolic acid tablet (OAT), O(3), YC and O(3) + YC, given either no particular pre-treatment, oral OAT, medical ozone rectal insulfflation every other day, oral YC, or oral YC plus medical ozone rectal insulfflation every other day, respectively, for 30 consecutive days. After pre-treatment, acute hepatic injury was induced in all dogs with a single-dose intraperitoneal injection of CCl(4). General condition and survival time were recorded. The biochemical and hematological indexes of alanine aminotransferase (ALT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), serum total bilirubin (TBIL), prothrombin time (PT), blood ammonia (AMMO), and blood urea nitrogen (BUN) were measured after CCl(4) injection. Hepatic pathological changes were also observed. Compared to the other four groups, the changes of group O(3) + YC dogs' general conditions (motoricity, mental state, eating, urination and defecation) could be better controlled. In group O(3) + YC the survival rates were higher (P < 0.05 vs group control). AST/ALT values were kept within a normal level in group O(3) + YC. Hepatic histopathology showed that hepatic injury in group O(3) + YC was less serious than those in the other four groups. Medical ozone combined with TCM YC could exert a protective effect on acute liver injury induced by CCl(4).

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC

A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.

Epidemiologie der chronischen Hepatitis C in Deutschland

D Background and Purpose: Little is known about the epidemiology of hepatitis C in Germany and in particular about the route of infection. The current study prospectively analyzed epidemiologic and clinical data of patients with chronic hepatitis C virus (HCV) infection. D Methods: A structured questionnaire was sent to primary care physicians in Germany. Of 13,287 questionnaires, 5,837 were sent back for analysis. D Results: Although the number of questionnaires sent out was proportional to the number of subjects living in the new and old states of Germany, only 9% were sent back from the new states; thus, the prevalence of hepatitis C is probably considerably lower in the new states compared with the old ones. The HCV-infected subjects originated from 92 different countries throughout the world: 63% were born in Germany, but 21% were from one of the former states of the USSR. Intravenous drug abuse was the most prevalent risk noted; there was a strong bias whereby physicians who cared for a large number of HCV-infected patients had a much higher proportion of subjects with i.v. drug abuse when compared to those who only cared for a few hepatitis C patients. In the latter group a history of infusion of blood products was approximately as frequent as a history of drug abuse. There was a high proportion of patients who had no risk factor for hepatitis C (25-42%). Fatigue was the most frequent symptom (nearly 60%), followed by loss of concentration and abdominal pain. The number of symptoms increased with a higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and thus presumably with the stage of liver fibrosis. D Conclusion: Hepatitis C should be excluded in all patients with elevated liver enzymes. In risk groups with a high prevalence of hepatitis C, the infection should be looked for even when liver enzymes are normal.

Liver function assessment in workers exposed to vinyl chloride

To investigate liver function in vinyl chloride workers and assess its relation with current/past occupational exposure to vinyl chloride monomer (VCM). A medical examination including the execution of liver function tests (LFTs) and liver ultrasonography was executed in a group of 757 workers with a long-standing service in the production of VCM/polyvinylchloride (PVC). Cumulative and maximum VCM exposures were calculated. History of viral hepatitis and alcohol intake were carefully investigated. Regression analysis explored the association between abnormal LFTs and a group of possible determinants (VCM cumulative and maximum exposure, BMI, age, history of viral hepatitis, alcohol and triglyceride levels). Also, synergistic effect between VCM and a history of hepatitis was analysed, as well as the possible association between VCM exposure and aspartate aminotransferase/alanine amino transferase (AST/ALT) ratio >1. Distribution of abnormal LFTs was also assessed in relation to the results provided by liver ultrasonography. The most frequently abnormal serum parameters were, in decreasing order: total cholesterol (27.3%), triglycerides (12.2%), total bilirubin (9.1%), gamma glutamil transpeptidase (GGT; 9.0%) and ALT (8.2%). The AST/ALT ratio >1 was present in 28.1% of workers. Abnormal LFTs were not found to be associated with current or past VCM exposure. High ALT resulted positively associated with BMI, AST with alcohol intake, GGT with alcohol intake and triglycerides. No synergistic effect on LFTs of exposure to VCM and a history of hepatitis was observed. The AST/ALT ratio >1 was not found to be associated with VCM exposure. The prevalence of abnormal LFTs was higher in case of liver steatosis (ALT) or periportal fibrosis (GGT), but not in case of pure hepatomegaly, as documented by ultrasonography. Liver function assessment only including LFTs is not able to detect VCM-induced liver damage, but reveals alterations due to non-occupational factors, such as dietary and/or metabolic disfunctions. The LFTs are however of importance to detect conditions that could recommend avoidance of exposure to VCM and are useful for medical counselling and health promotion purposes.

Helium pneumoperitoneum specifically alters liver function tests

Abdominal surgery is now commonly accomplished laparoscopically using carbon dioxide (CO 2) insufflation. Increased intraabdominal pressure (IAP) decreases hepatic blood flow, portal vein pressure, and hepatic pH. Furthermore, CO 2 pneumoperitoneum worsens systemic acidosis. Liver function tests (LFTs) are often elevated following laparoscopic cholecystectomy albeit without any clinical significance. Helium (He) may be an alternative to CO 2 pneumoperitoneum. We examined effects of IAP and the potential benefits afforded by He pneumoperitoneum on hepatocellular toxicity. Fifty male Sprague-Dawley rats were randomized to anesthesia control, CO 2 pneumoperitoneum at 4 mmHg, CO 2 pneumoperitoneum at 8 mmHg, CO 2 pneumoperitoneum at 12 mmHg, and Helium pneumoperitoneum at 12 mmHg. Rats received pneumoperitoneum or control procedure for 30 min. Alkaline phosphatase (AlkPhos), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured at baseline, 2 h, and 24 h following pneumoperitoneum. Helium increased ALT and AST at 2 h compared to all other groups. By 24 h AST was elevated in all groups except the He group. These differences between He and all other groups were not seen in AlkPhos. CO 2 pneumoperitoneum did not cause a significant change in LFTs compared to control regardless of changes in IAP, at any time point. Helium pneumoperitoneum acutely increases AST and ALT without altering AlkPhos. These results imply that hepatocellular function is altered by He without significantly influencing biliary function, thus suggesting a highly specific mechanism of action. Furthermore, CO 2 pneumoperitoneum does not cause hepatocellular damage in the acute postoperative period regardless of IAP. TABLE—ABSTRACT P81 Alk Phos ALT AST t = 0 t = 2 h t = 24 h t = 0 t = 2 h t = 24 h t = 0 t = 2 h t = 24 h Control 200 193 219 42 42 48 74 78 137 CO 2 4 mmHg 217 189 198 34 30 35 73 78 118 CO 2 8 mmHg 278 268 319 41 39 40 76 82 115 CO 2 12 mmHg 221 215 248 44 42 44 78 90 138 He 12 mmHg 248 215 243 37 55 34 68 109 77

Nonalcoholic fatty liver disease in patients with type 2 diabetes

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is reported commonly in patients with type 2 diabetes mellitus (DM), which has been suggested as a risk factor for the progressive form of NAFLD, or nonalcoholic steatohepatitis. The aim of this study was to assess the outcome of patients with NAFLD and DM. Methods: A cohort of patients with NAFLD was identified, and patients with other causes of liver disease (alcohol, medication, etc.) were excluded. Clinical, pathological, and mortality data were available for this cohort. Patients were categorized and compared according to the presence or absence of DM. Results: Of 132 patients with NAFLD, 44 patients (33%) had an established diagnosis of DM. Patients with DM were older and had greater serum glucose and triglyceride levels and a greater aspartate aminotransferase-alanine aminotransferase ratio. Liver biopsy specimens from patients with DM showed more vacuolated nuclei and acidophilic bodies. Cirrhosis (histological or clinical) occurred in 25% of patients with DM (11 of 44 patients) and NAFLD compared with only 10.2% (9 of 88 patients) of patients without DM with NAFLD ( P = 0.04). After adjusting for potential confounders (age, body mass index, and the presence of cirrhosis), both overall mortality (risk ratio [RR], 3.30; 95% confidence interval [CI], 1.76–6.18; P = 0.002) and mortality related to liver disease (RR, 22.83; 95% CI, 2.97–175.03; P = 0.003) were greater in diabetic patients with NAFLD. Markers of hepatic dysfunction (low albumin level, high total bilirubin level, and prolonged prothrombin time) were the only independent predictors of increased mortality. Conclusions: Patients with NAFLD and DM are at risk for the development of an aggressive outcome, such as cirrhosis and mortality. This study supports the potential role of insulin resistance in the development of poor clinical outcomes in patients with NAFLD.

Validity and Clinical Utility of the Aspartate Aminotransferase–Alanine Aminotransferase Ratio in Assessing Disease Severity and Prognosis in Patients With Hepatitis C Virus–Related Chronic Liver Disease

The aspartate aminotransferase-alanine aminotransferase ratio (AST/ALT ratio) has been used to noninvasively assess the severity of disease in patients with chronic liver disease (CLD). We previously demonstrated that progressive liver functional impairment is associated with an increase in the AST/ALT ratio. To evaluate the reproducibility and transportability of the AST/ALT ratio in a large cohort of patients with different degrees of hepatitis C virus (HCV)-related CLD, to confirm the correlation between progressive impairment of liver function and increase in the AST/ALT ratio, to evaluate whether diagnostic accuracy of the ALT/AST ratio can be improved by using it with other biochemical variables, and to assess the 1-year prognostic capability of the AST/ALT ratio in patients with liver cirrhosis. We retrospectively evaluated 252 patients with HCV-related CLD. The AST/ALT ratio was correlated with the degree of liver fibrosis in patients with chronic hepatitis and with the Child-Pugh score in patients with cirrhosis. All patients had undergone monoethylglycinexylidide (MEGX) testing to evaluate liver function. We assessed the prognostic ability of the AST/ALT ratio in a subset of 63 cirrhotic patients who were followed up for at least 1 year. The AST/ALT ratio was more frequently 1 or higher in cirrhotic patients (P<.001). There was a significant correlation between MEGX values and the AST/ALT ratio (r(s) = -0.621, P<.001). Multivariate stepwise logistic analysis showed that AST/ALT ratio, platelet count (PLT), MEGX values, and prothrombin activity were independently associated with the presence of cirrhosis. Combined assessment of the AST/ALT ratio and/or PLT obtained 97.0% positive predictive value and 97.9% negative predictive value for the diagnosis of cirrhosis. The AST/ALT ratio had 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients who died within 1-year of follow-up. The AST/ALT ratio is both reproducible and transportable in patients with HCV-related CLD. The AST/ALT ratio is correlated with both histologic stage and clinical evaluation. Progressive liver functional impairment is reflected by an increase in the AST/ALT ratio. Noninvasive evaluation by means of the combined AST/ALT ratio and PLT assessment misclassifies only a few cirrhotic patients. In cirrhotic patients, the AST/ALT ratio provides medium-term prognostic information that is no different from that provided by established prognostic scores.

Revisiting the AST/ALT Ratio in Hepatitis C

Results of a study published in 1998 showed that at 1 center in Boston an aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio ≥1.0 had