Abnormal Alanine Aminotransferase Values Research Articles

Study on liver histopathology of chronic HBV infected patients with different normal ALT values.

Comparison of liver histopathological findings to explore the occurrence of liver inflammation in patients with chronic hepatitis B (CHB) under different alanine aminotransferase (ALT) normal values. The patients who were diagnosed as chronic hepatitis B virus (HBV) infection by liver histopathology at the Department of Pathology, Beijing Ditan Hospital due to clinical difficulty in defining the degree of liver inflammation or fibrosis were retrospectively enrolled from May 2008 to November 2020. Study of the incidence of significant hepatic histopathology in enrolled patients according to different ALT normal values. Using logistic regression to investigate the relevant factors of significant hepatic histopathology. A total of 1474 patients were enrolled, 56.20% of the patients were male, and the overall patients' age was 36.80 ± 10.60 years. 39.00% of patients had liver inflammation grade G > 1, 34.70% liver fibrosis stage S > 1, and 48.17% patients had significant hepatic histopathology (G > 1 and/or S > 1). Among patients with normal ALT values, 36.40% and 40.40% had significant hepatic histopathology by American Association for the Study of Liver Diseases (AASLD) criteria and Chinese guideline criteria, respectively, but the difference was not statistically significant (χ2 = 3.38, P =0.066). In contrast, among patients with abnormal ALT values, 58.90% and 62.20% of patients had significant hepatic histopathology by AASLD criteria and Chinese guideline criteria, respectively, with no significant difference (χ2 = 2.28, P =0.131). ALT (P <0.001, OR=1.019), hepatitis B surface antigen (HBsAg) (P <0.001, OR=0.665) and hepatitis B e antigen (HBeAg) status (P <0.001, OR=2.238) were relevant factors in the occurrence of significant hepatic histopathology. ALT was positively corelated with grade of inflammation G (r =0.194, P <0.001) and negatively correlated with liver fibrosis stage S (r =-0.066, P =0.021). Our study found no statistically significant differences in the presence of significant hepatic histopathology under the two ALT criteria. ALT, HBsAg and HBeAg status were related to the occurrence of significant hepatic histopathology.

S1120 When Your Lab Didn’t Read the Guidelines: The Ability of Physicians in a Teaching Hospital Clinic to Identify Abnormal Alanine Aminotransferase (ALT) Values

Introduction: ACG guidelines define normal ALT as 29 to 33 for males and 19 to 25 for females. An elevated ALT, even if borderline, warrants consideration as to the cause, and monitoring for worsening. However, different laboratories use different reference values for normal, and many report ALTs greater than 25 or 33 as normal. Our hospital’s lab reports ALT 6-55 as normal. In this study, we aimed to assess physicians’ identification of abnormal ALT values, particularly in instances when the lab did not identify it as abnormal (by bolding). Methods: We reviewed the charts of 4965 patients seen in Internal Medicine (IM) and GI clinics to identify patients with elevated ALTs. Only the first instance of elevated ALT was included for each patient. We excluded patient who had a history of liver disease. We identified the patients who had ALTs that were abnormal but not marked as such by the laboratory. For each patient, we reviewed the clinic notes to find any comment or plan for work-up. Results: Results are summarized in the chart and table. 1018 patients with elevated ALT and no history of liver disease were identified and included. Elevated ALT was identified by the physician in 29.1% of patients. Of elevated ALT values that were less than 55, only 31/491 were identified. Of these 31 patients, 11 were not seen again and 5 had no additional testing. One patient underwent liver biopsy. The rest had an ultrasound and serologic testing. After work-up, two patients were presumed to have alcoholic liver disease, 5 NAFLD, one was diagnosed with choledocholithiasis, and 3 were diagnosed with DILI. Furthermore, there was a significant difference in the identification of abnormal ALTs between 50-55 (not bolded) and ALTs between 56-64 (bolded): ALT of 50-55 was identified as abnormal in 16.4% of visits, while ALT of 56-64 in 39.7% (P-value .005). Of note, GI physicians were significantly more likely to identify elevated ALT values than IM physicians (see table). Conclusion: Physicians were more likely to identify an abnormal ALT if it was bolded. In both clinics, non-bolded ALTs were largely ignored. Amongst the patients whose non-bolded elevated ALT were identified, most received additional testing and were found or presumed to have modifiable etiologies. This study demonstrates the need for physicians to better familiarize themselves with normal ranges of liver tests, and consider the need for further evaluation or monitoring when an ALT value is abnormal even if their laboratory does not identify it as such.Table 1Figure 1.: Identification of Elevated ALT as Abnormal. Blue bar shows GI clinic; Orange bar shows IM clinic; Gray bar shows Total

ADME gene polymorphisms do not influence the pharmacokinetics of docetaxel: Results from a population pharmacokinetic study in Indian cancer patients.

BackgroundPharmacokinetics (PK) of docetaxel is characterized by high inter‐individual variability (IIV). While covariate models that explain the PK variability of docetaxel exist, not much is known about the effects of genetic variations on docetaxel disposition.MethodsFifty patients with head and neck or prostate cancer were enrolled of whom two patients withdrew consent before the start of the study. Docetaxel was administered at either 50 or 75 mg/m2 as intravenous infusion over 1 h. One pharmacogenetic sample and a series of PK samples, either intensive (N = 5; 13 samples each) or sparse (N = 43; 6 samples each), were collected from each patient. Docetaxel levels were estimated using a validated HPLC method. Polymorphic loci on the Absorption, Distribution, Metabolism, and Elimination (ADME) genes were identified using the PharmacoScan array platform. Population pharmacokinetic analysis was carried out using NONMEM v7.2.ResultsDocetaxel PK was well characterized by a three‐compartment model. Clearance (Cl) was found to be 18 L/h with an IIV of 45.3%. None of the genetic variants showed significant covariate effect on the Cl of docetaxel. Patients with abnormal alanine aminotransferase (ALT) were found to have 25% lower Cl as compared to patients with normal ALT values. However, the covariate effect could not be established in the final model possibly due to lack of adequate number of patients with abnormal ALT.ConclusionGenetic polymorphisms in the ADME gene do not explain the IIV in PK of docetaxel. However, patients with abnormal liver function might require dose reduction.Clinical trial registration: Not applicable since participants in this study received treatment that was standard of care.

Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Our aim was to study the long-term effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on NAFLD/NASH. Between 2008 and 2015, 3813 patients had an intraoperative liver biopsy performed at the time of primary RYGB and SG at a single academic center. Utilizing strict inclusion criteria, 487 patients with biopsy-proven NAFLD who had abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values (≥ 40IU/L) at baseline were identified. Matching of SG to RYGB patients (1:4) was performed via logistic regression and propensity scores adjusting for clinical and liver histological characteristics. Changes in liver function tests (LFTs) at least 1year after surgery were compared to baseline values and between the surgical groups. A total of 310 (weighted) patients (SG n = 62, and RYGB n = 248) with a median follow-up time of 4years (range, 1-10) were included in the analysis. The distribution of covariates was well-balanced after propensity matching. In 84% of patients, LFT values normalized after bariatric surgery at the last follow-up time. The proportions of patients having normalized LFT values did not differ significantly between the SG and RYGB groups (82% vs. 84%, p = 0.66). The AST decreased from (SG: 49.1 ± 21.5 vs. RYGB: 49.3 ± 22.0, p = 0.93) at baseline to (SG: 28.0 ± 16.5 vs. RYGB: 26.5 ± 15.5, p = 0.33) at the last follow-up. Similarly, a significant reduction in ALT values from (SG: 61.7 ± 30.0 vs. RYGB 59.4 ± 24.9, p = 0.75) at baseline to (SG: 27.2 ± 21.5 vs. RYGB: 26.1 ± 19.2, p = 0.52) at the last follow-up was observed. In patients with biopsy-proven NAFLD/NASH, abnormal LFTs are normalized in most SG and RYGB patients by the end of the first postoperative year and remain normal until the last follow-up. This study also suggests that both bariatric procedures are similarly effective in improving liver function.

Hyperemesis gravidarum with acute liver injury and positive feto-maternal outcome

This is a case report of Hyperemesis Gravidarum (HG) with a distinctly abnormal elevated ALT and AST values, in association with intractable nausea and vomiting. A 26-year-old woman G2P1A0 with a 9-week gestational age and no significant past medical history, presented with intractable nausea and vomiting despite medication use for three weeks. Despite administration of Vitamin B6, the symptoms persisted. During this period, the patient was unable to tolerate solids or liquids, and experienced progressive weakness, fatigue, and non-radiating epigastric pain. The patient was admitted to the Brooklyn Hospital Center Family Medicine service and found to have notable electrolyte disturbances, and remarkable transaminitis, with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values of 3400 IU/L and 717 IU/L respectively. All alternative diagnoses were ruled out. Ultimately, transaminitis resolved and mother an baby are doing well. This case report describes the typical clinical presentation of HG with acute liver injury and positive feto-maternal outcome.

Teriflunomide for multiple sclerosis in real-world setting.

Teriflunomide 14mg is a once-daily oral disease-modifying treatment for relapsing-remitting multiple sclerosis. We examined adverse event (AE) profile and efficacy in real life. In this observational cohort study, we retrospectively examined 1521 blood samples and data of 102 patients followed for up to 28months. The number of female patients starting teriflunomide peaked in the fifth decade, 10years later compared to male patients (P<.001), reflecting pregnancy concerns. Seventy-six percentages of patients shifted to teriflunomide from treatment with interferon-beta. Expanded disability status scale improved in 11% of patients (18.2±3.6months follow-up) and remained constant in 67.5% (15±5.3months follow-up). Of ten relapses, three occurred within 6months after starting treatment. Seventeen patients (16.5%) discontinued teriflunomide: 53% because of AEs and 29% because of relapse. Levels of alanine aminotransferase (ALT) remained normal in 95.3% of the blood samples and remained below 1.5 times the upper limit of normal in 91% of the 4.7% abnormal samples. One-third of the patients had abnormal ALT values at least once. Haematological abnormalities were found in <4% of the blood samples, but at least one abnormal value was observed in up to 21% of the patients. Efficacy and safety of teriflunomide in real-life setting support data obtained by the pivotal trials. Laboratory abnormalities are rare among the large number of samples, but patients may commonly have a single mild, abnormal value if frequently tested.

Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response.

BackgroundThe purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR).Methods and FindingsSeven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN) at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and 235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45–3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16–2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35–4.09; P = 0.002).ConclusionsUse of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved.

Cardiorespiratory Fitness, But Not Central Obesity or C-Reactive Protein, Is Related to Liver Function in Obese Children

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent complications associated with excess adiposity. Its pathogenesis is complex and there are multiple factors that may contribute to it. To analyze whether cardiorespiratory fitness (CRF), waist circumference (WC), and C-reactive protein (CRP) are associated with alanine aminotransferase (ALT) in children with obesity. 79 overweight/obese children of both genders, 11-13 year-olds, with abnormal serum ALT from Porto public schools comprised the sample. Measurements included CRF (20-m Shuttle Run Test), WC (NHANES protocol), CRP and ALT (Cholestech LDX analyzer). Logistic regression adjusted for gender, maturation, and weight with ALT levels as dependent variable (risk vs. non risk), and WC (risk vs. non risk), CRP (risk vs. non risk), and CRF (fit vs. unfit) as independent variables. Level of significance was set at 95%. Logistic regression showed that obese fit children were less likely to have abnormal ALT values (OR=.031) In obese children, higher cardiovascular fitness appears to reduce the chance of decreased liver function.

Early Increased Ficolin‐2 Concentrations are Associated with Severity of Liver Inflammation and Efficacy of anti‐Viral Therapy in Chronic Hepatitis C Patients

Ficolin-2 is a kind of human serum complement lectin with a structure similar to mannan-binding lectin (MBL), and it has been implicated in innate immunity. Recent studies have shown that complement pathway activation may contribute to hepatitis. However, the relationship between ficolin-2 and viral hepatitis remains largely elusive. The aim of this study was to determine the dynamics of ficolin-2 in patients with chronic hepatitis C. Forty nine patients who had not yet received therapy [24 patients with abnormal alanine aminotransferase (ALT) levels (>40 U/L) and 25 patients with normal ALT levels (≤ 40 U/L)], 28 patients with hepatitis C who received therapy for 2 weeks and 16 patients received therapy for a full month or longer were included in the study. A sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the ficolin-2 concentrations in all serum samples of patients and 42 healthy donors. We found the concentrations of ficolin-2 were significantly higher in chronic hepatitis C patients with abnormal ALT values than in chronic hepatitis C patients with normal ALT values and healthy controls. Ficolin-2 concentrations in chronic hepatitis C patients with abnormal ALT values were positively correlated with ALT levels (P < 0.05). After therapy, the concentrations of ficolin-2 decreased and accompany with ALT and Hepatitis C virus (HCV) RNA levels. Then, we found ficolin-2 concentrations in rapid viral response (RVR) group decreased significantly (P < 0.05), while in non-RVR group, ficolin-2 decreased slightly (P > 0.05). Our findings suggest that early increased ficolin-2 is highly correlated with hepatic inflammation and rapid viral response.

Fitness and metabolic syndrome in obese fatty liver children

Background: Metabolic Syndrome (MS) is highly prevalent among obese children with fatty liver. However, it is well-known that there is a lower prevalence of MS in individuals with higher cardiorespiratory fitness (CRF).Aim: To analyse the association between CRF with features of the MS in obese children that present fat liver indicators, namely abnormal alanine aminotransferase (ALT) values.Methods: A total of 79 obese students (40 girls), 10–11 year-olds ( ± 0.60), with abnormal serum ALT from Porto public schools comprised the sample. Measurements included CRF (20-metre Shuttle Run Test), Metabolic Risk Factors (MRF), according to MS International Diabetes Federation criteria, ALT values (Cholestech LDX® analyser) and maturational stage (Tanner criteria). Logistic regression analysis was used to determine the influence of CRF on MRF adjusted for sex, maturation, and BMI.Results: The logistic regression showed that, despite being classified as being obese and presenting abnormal levels of ALT, those classified as fit were less likely to have MS than their unfit counterparts (OR = 0.52; p ≤ 0.05).Conclusion: Obese-fit children with abnormal ALT values have a significant reduction in the likelihood to be classified as having MS, even after adjustments for gender, maturation and BMI, Thus, CRF might be an important factor for tackling fatty liver among obese.

A preliminary study of apparent diffusion coefficient in chemotherapy-induced liver damage

ObjectivesTo investigate changes in the hepatic apparent diffusion coefficient (ADC) in patients undergoing chemotherapy. MethodsWe enrolled 54 patients (25 women; mean age 57.0±13.1 years, range 29–89 years) undergoing chemotherapy for tumor and 10 controls (7 women; mean age 55.1±17.5 years, range 23–81 years). The patients were tested for serum alanine aminotransferase (ALT) activity (abnormal, normal) and fatty liver. Hepatic ADC values were compared among controls, patients and subgroups. Pearson correlation coefficient was used to assess the correlation between ADC and ALT activity. ResultsHepatic ADC0,850 (×10−3mm2/s) was lower for patients than controls (1.14±0.18 vs. 1.28±0.12, P=0.02) and was lower for patients with than without fatty liver and controls (1.01±0.06 vs. 1.18±0.18 and 1.28±0.12, respectively, all P<0.01), with no significant difference between patients without fatty liver and controls (P=0.07). ADC0,850 was lower for patients with abnormal ALT than normal ALT activity and controls (0.99±0.06 vs. 1.17±0.18 and 1.28±0.12, respectively, all P<0.05), with a significant difference also being seen between patients with normal ALT activity and controls (P=0.04). Hepatic ADC0,850 was not correlated with ALT activity in patients (r=-0.24, P=0.08). ConclusionsAlthough ADC did not correlate with ALT values, it did distinguish patient likely to have chemotherapy-induced liver damage as indicated by abnormal ALT values or fatty liver. These mechanisms need to be disentangled.

Characterization of elevated alanine aminotransferase levels during pegylated‐interferon α‐2b plus ribavirin treatment for chronic hepatitis C

Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon. Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis. Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients. Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b. Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.

High prevalence of abnormal alanine and aspartate aminotransferases in a “worried-well” population in the United Kingdom: Rationale for a liver screening program?

We read with great interest the recent article by Lee et al.1 suggesting increased risk of mortality of patients with elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). However, the prevalence of abnormalities of ALT and AST in the general population remains undetermined. A particular group of interest is the “worried-well” population. We would like to report the results of ALT and AST tests in a population of “normal” worried-well who presented themselves for testing using a commercially available “do-it-yourself” kit.2 Once the samples were received in the laboratory, AST and ALT values were measured using a standard colorimeter enzymatic method. The aim of this study was to determine the prevalence of abnormal ALT and AST values in this population that had no known underlying medical disorders. The study population consisted of 1039 subjects, comprising 561 female and 478 male subjects, all over 18 years of age (mean age of 45.3 ± 11.8 years old). Applying a cut-off for the upper limit of normal (ULN), as used in the study by Lee et al.1 (ALT of 45 U/L for men and 29 U/L for women and AST of 31 U/L for both men and women), the percentage of abnormal ALT values in our study population was 12.5% (12.1% 1× ULN; 0.4% 3× ULN) for men and 9.8% (8.6% 1–2× ULN; 0.7% 2–3× ULN; 0.5% ≥3× ULN) for women. Percentage of abnormal AST values was 57% (50.3% 1–2× ULN; 5.3% 2–3× ULN; 1.4% ≥3× ULN) in men and 71.4% (60.9% 1–2× ULN; 8.6% 2–3× ULN; 1.9% ≥3× ULN) in women. However, it is likely that the ULN for ALT should be lower than those used by Lee et al., because they included people with nonalcoholic fatty liver disease in their standard normal population.1, 3 The study by Prati et al.4 in healthy Italian first-time blood donors, with no previous medical disorders and a body mass index less than 25 kg/m2, with normal levels of cholesterol and glucose, and with no known drug history, a better cut-off point for the limit of normality for ALT was 30 U/L for men and 19 U/L for women. These values are closer to the ones in the Korean study5 (30 U/L ALT; 31 U/L AST). Using this cut-off, the proportion of patients with an abnormal ALT test value would be 32.6% and 35.3% for men and women, respectively. Of those, 5.8% of the men and 3.5% of the women are above twice the ULN. Plots of ALT versus AST (Fig. 1A,B) reveal a poor correlation between these two enzymes, indicating possibly different pathophysiological processes; the group having a high ALT/AST ratio are more likely to have nonalcoholic fatty liver disease, whereas those with a high AST/ALT ratio are likely to have alcohol-related liver disease.6-8 Plots represent ALT levels versus AST levels in (A) “well-worried” men and (B) “well-worried” women. Cut-off proposed by Kim et al.5 and Prati et al.4 The results of this study reveal an unexpectedly high prevalence of abnormalities in ALT and AST in the worried-well population in the United Kingdom. If the data presented by Lee et al. are representative of the population at large, more than 50% of the population studied are at higher risk of mortality compared with age-matched and sex-matched controls. Because the stated reason for undertaking the test was alcohol misuse in the vast majority of patients, this awareness of abnormal liver function test may allow targeted intervention to prevent progression to chronic liver disease and strongly supports Kim's justification for screening.8 However, before such programmes can be instituted widely, one needs to identify the ULN for different ages and populations. Because it is accepted that a proportion of patients with significant underlying liver disease can have normal ALT and AST, it will be necessary to define the most effective screening method.9, 10 Dr. García-Romero is supported by a grant from the Government of Spain. Diana García-Romero* , J. Anastassiou*, Gillian Hart , Rajeshwar Mookerjee*, Rajiv Jalan*, * Institute of Hepatology, Division of Medicine, University College London and UCL Hospitals, London, UK, Unit for the Clinical Management of Digestive Diseases, Valme University Hospital, Seville, Spain, YorkTest Laboratories Ltd., York, UK.

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.

Hepatotoxicity Associated with Acarbose Therapy

To report a case of acarbose-induced hepatotoxicity and compare other reported cases from the literature. A 57-year-old woman with type 2 diabetes mellitus for about 10 years had been treated with insulin glargine 20 units/day since December 19, 2002. Acarbose 100 mg 3-times-daily add-on therapy for inadequate glycemic control was started on June 5, 2003. Six months later, the woman complained of gastrointestinal discomfort; the acarbose dose was decreased to 50 mg 3 times daily thereafter. Laboratory examination later revealed alanine aminotransferase (ALT) 640 U/L (upper reference value 55). To elucidate the possibilities of adverse reactions caused by concurrent use of nutritional supplements and medication, we discontinued propolis extract, Ginkgo biloba, placeta extract, and estrogen. Although no remarkable symptoms were noted thereafter, the abnormal ALT values persisted, and no definite viral or autoimmune etiologies were identified. Acarbose was discontinued in August 2004; aspartate aminotransferase and ALT values returned to normal in October 2004. In addition to ruling out other possible etiologic factors, we assessed the probability of acarbose-induced hepatotoxicity by observing the close time relationship between drug administration and the development of signs and symptoms, as well as the close time relationship between drug withdrawal and the normalization of abnormal liver function test values. An objective causality assessment revealed that an adverse drug reaction was probable as determined by both the Naranjo probability scale and the Roussel Uclaf Causality Assessment Method score. Although acarbose-induced hepatotoxicity appears to be uncommon, diabetic patients receiving long-term acarbose therapy should be closely monitored for this adverse effect.

Abnormal aminotransferase activity in women with polycystic ovary syndrome

Alanine aminotransferase (ALT) activity was abnormal in 30% of 70 female infertility patients with polycystic ovary syndrome in whom causes other than nonalcoholic fatty liver disease were excluded by history and serum testing. Women with elevated ALT had significantly higher body mass index, waist circumference, serum triglycerides, total cholesterol-to-HDL-cholesterol ratio, and degree of insulin resistance.

Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon α-2b for chronic hepatitis type C: Results of a multicenter randomized trial

Background/Aims: To examine the effect of prolonged treatment with different doses of interferon α-2b on the relapse rate in patients with chronic hepatitis C.Methods: One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3 000 000 Units (3 MU) of interferon α-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total = 2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total = 2 years). Follow-up continued for 2 years after therapy withdrawal.Results: Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001).Conclusions: About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond signifiantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.

Treatment of Relapses in Patients With Chronic Hepatitis C With Recombinant α-Interferon

Fifty-six patients with chronic hepatitis C who responded to 6 months’ treatment with recombinant α-interferon (rIFNα), 3MU 3 times weekly, were randomly enrolled into 2 groups (A and B) and followed up for 38 months in the following manner: patients in group A, who again had increases in alanine aminotransferase (ALT) levels, received a second 6-month course of the same type and dose of interferon (IFN); patients who showed a further relapse in the next 12 months were immediately submitted to a third 6-month course with the same IFN and followed up to the sixth month after IFN withdrawal. Patients in group B did not receive any treatment after the first course, and were used as the control group. Patients with other potential causes of chronic liver disease, with histological diagnosis of cirrhosis or with abnormal ALT levels were excluded. Liver function tests were performed every 2 months. Serum HCV-RNA was determined every 12 months when the patients continued to show normal ALT levels, and it was evaluated before and after IFN retreatment if ALT levels again increased. There were 5 dropouts (8.9%). 41.1% of the patients did not show relapses. At the end of the study, 7 (43.7%) of the 16 patients, who were retreated because of relapse, again showed abnormal ALT values, while in the control group there were 14 (58.3%) relapses. This difference was not statistically significant. A complete response, exclusively defined by a normalisation of aminotransferase levels with disappearance of serum HCV-RNA, was only achieved in the patients with undetectable HCV-RNA at the beginning of the study: in fact HCV-RNA, if present in serum after the first IFN course, did not disappear after the following cycles. We concluded that the retreatment of relapses with rIFNα was of little benefit, even if it could lead to a complete response in some patients with undetectable serum HCV-RNA after the first IFN course.

Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities

Hepatitis C virus (HCV) infection persists for an indefinite length of time in a major proportion of patients, inducing chronic liver lesions that evolve to cirrhosis and hepatocellular carcinoma (HCC) in approximately 20% of cases. We studied HCV viremia and genotypes by reverse transcription-polymerase chain reaction (RTPCR) in 341 consecutive anti-HCV-positive patients. Of these, 167 patients had persistently normal or near normal alanine aminotransferase (ALT) levels (fluctuations ≤5 IU above the upper limit of normal); the remaining 174 patients presented with elevated ALT and histological evidence of chronic liver disease. Seventy percent of patients with normal ALT values had circulating HCV RNA despite the absence of biochemical indicators of liver damage and mild histological forms of chronic hepatitis were detected in most patients who underwent liver biopsy. Isolated genotype III infection was significantly more prevalent in this patient group with respect to control patients with abnormal ALT values (70% vs. 39%; P <.001). Conversely, isolated genotype II was more frequently found in patients with elevated ALT values and evidence of chronic liver disease (45% vs. 23%; P < .01) and it was progressively more represented in advanced liver disease, such as cirrhosis and HCC. Virological features of HCV infection might be associated with different clinical manifestations, suggesting a potential prognostic significance on disease outcome.

Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities

Hepatitis C virus (HCV) infection persists for an indefinite length of time in a major proportion of patients, inducing chronic liver lesions that evolve to cirrhosis and hepatocellular carcinoma (HCC) in approximately 20% of cases. We studied HCV viremia and genotypes by reverse transcription-polymerase chain reaction (RT-PCR) in 341 consecutive anti-HCV-positive patients. Of these, 167 patients had persistently normal or near normal alanine aminotransferase (ALT) levels (fluctuations ≤5 IU above the upper limit of normal); the remaining 174 patients presented with elevated ALT and histological evidence of chronic liver disease. Seventy percent of patients with normal ALT values had circulating HCV RNA despite the absence of biochemical indicators of liver damage and mild histological forms of chronic hepatitis were detected in most patients who underwent liver biopsy. Isolated genotype III infection was significantly more prevalent in this patient group with respect to control patients with abnormal ALT values (70% vs. 39%; P &lt; .001). Conversely, isolated genotype II was more frequently found in patients with elevated ALT values and evidence of chronic liver disease (45% vs. 23%; P &lt; .01) and it was progressively more represented in advanced liver disease, such as cirrhosis and HCC. Virological features of HCV infection might be associated with different clinical manifestations, suggesting a potential prognostic significance on disease outcome. (Hepatology 1995;21:285-290.)