Lower Alanine Aminotransferase Values Research Articles

Low Serum Alanine Aminotransferase Blood Activity Is Associated with Shortened Survival of Renal Cell Cancer Patients and Survivors: Retrospective Analysis of 1830 Patients

Background: Sarcopenia is characterized by a loss of muscle mass and function and is often associated with frailty, a syndrome linked to physical disability and shortened survival in various patient populations, including cancer patients. Low serum alanine aminotransferase (ALT) values, serving as a biomarker for sarcopenia, were previously associated with frailty and shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods: This was a retrospective analysis of RCC patients and survivors, both in- and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. Results: We identified records of 3012 RCC patients. The cohort included 1830 patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3%) had ALT < 17 IU/L, with a mean ALT value of patients within the low-ALT group of 11.79 IU/L, while the mean value in the higher ALT level group was 24.44 IU/L (p < 0.001). Patients in the low-ALT group were older (67.9 vs. 63.7 years; p < 0.001) and had lower BMIs (26.6 vs. 28; p < 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p < 0.001), higher serum creatinine (1.49 vs. 1.14; p < 0.001) and higher platelet to lymphocyte ratios (178 vs. 156; p < 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46–2.02, p < 0.001). In a multivariate model controlled for age, gender, hemoglobin, platelets, LDH, neutrophil to lymphocyte ratios and platelet to lymphocyte ratios, low ALT levels were still associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08–1.51; p = 0.005). Conclusion. Low ALT values, associated with sarcopenia and frailty, are also associated with shortened survival in RCC patients, and survivors and could potentially be applied for optimizing individual treatment decisions.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.

Low Alanine Aminotransferase as a Marker for Sarcopenia and Frailty, Is Associated with Decreased Survival of Bladder Cancer Patients and Survivors-A Retrospective Data Analysis of 3075 Patients.

Sarcopenia is characterized by the loss of muscle mass and function and is associated with frailty, a syndrome linked to an increased likelihood of falls, fractures, and physical disability. Both frailty and sarcopenia are recognized as markers for shortened survival in a number of medical conditions and in cancer patient populations. Low alanine aminotransferase (ALT) values, representing low muscle mass (sarcopenia), may be associated with increased frailty and subsequently shortened survival in cancer patients. In the current study, we aimed to assess the potential relationship between low ALT and shorter survival in bladder cancer patients and survivors. This was a retrospective analysis of bladder cancer patients and survivors, both in and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. A total of 5769 bladder cancer patients' records were identified. After the exclusion of patients with no available ALT values or ALT levels above the upper normal limit, the final study cohort included 3075 patients (mean age 73.2 ± 12 years), of whom 80% were men and 1362 (53% had ALT ≤ 17 IU/L. The mean ALT value of patients within the low ALT group was 11.44 IU/L, while the mean value in the higher ALT level group was 24.32 IU/L (p < 0.001). Patients in the lower ALT group were older (74.7 vs. 71.4 years; p < 0.001), had lower BMI (25.8 vs. 27; p < 0.001), and their hemoglobin values were lower (11.7 vs. 12.6 g/dL; p < 0.001). In a univariate analysis, low ALT levels were associated with a 45% increase in mortality (95% CI 1.31-1.60, p < 0.001). In a multivariate model controlling for age, kidney function, and hemoglobin, low ALT levels were still associated with 22% increased mortality. Low ALT values, indicative of sarcopenia and frailty, are associated with decreased survival of bladder cancer patients and survivors and could potentially be applied for optimizing individual treatment decisions.

Low Alanine-Aminotransferase Blood Activity Is Associated with Increased Mortality in Chronic Lymphocytic Leukemia Patients: A Retrospective Cohort Study of 716 Patients.

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients' blood counts and cytogenetic anomalies-all are features of the disease rather than of the patient. Addressing the route of personalized rather than precise medicine, we refer to the assessment of patients' status of sarcopenia and frailty. Low alanine aminotransferase (ALT) was already shown to function as a surrogate marker for sarcopenia and frailty. We decided to find a possible correlation between low ALT values and poor prognosis of CLL patients. This is a retrospective cohort study of CLL patients treated in a large, tertiary medical center, as outpatients or inpatients. Their frailty status was evaluated in a retrospective manner. We defined patients with ALT below 12 IU/L as frail and divided our cohort into two groups including a low ALT level group (ALT < 12) and a normal ALT level group (ALT ≥ 12). Overall, our final analysis included 716 CLL patients, of which 161 (22.5%) had ALT levels lower than 12 IU/L. There was no significant difference in patients' age between the two groups. Patients with the low ALT had a lower hemoglobin concentration (median 10.8 g/dL [IQR = 2.7] vs. 12.2 [IQR = 3.1]; p < 0.001) and a higher proportion of patients were classified as Binet C score [48.4% vs. 31.1%]; p < 0.001). Frail CLL patients' survival was significantly shorter when compared to non-frail patients, in both the univariate [HR = 1.6 [95% confidence interval, CI 1.23, 2.0]; p < 0.01] and multivariate analyses [HR = 1.3 [95% CI 1.0, 1.7]; p = 0.03]. Sarcopenia and frailty assessment, based on blood ALT measurements, could potentially point out differences in CLL patients' prognoses. Such assessment could serve the purpose of treatment personalization of CLL patients.

The Prognostic Role of In-Hospital Mortality Predictors and De Ritis Ratio in Patients with Upper Gastrointestinal System Bleeding

Objective: We aimed to evaluate the prognostic significance of the aspartate aminotransferase(AST) / alanine aminotransferase (ALT) named as (De Ritis) ratio in patients hospitalized in the intensive care unit with the diagnosis of upper gastrointestinal (GI) bleeding. Method: We retrospectivelyanalyzed the clinical and laboratory data of 243 patients admitted with upper GI bleeding to the intensive care unit of our tertiary hospital between January 2018 and April 2022. The potential prognostic parameters between survivors and non-survivors groups and then between low De Ritis and High De Ritis groups were compared. The effect of the De Ritis ratio on in-hospital mortality was investigated by logistic regression analysis. Results: Of the two hundred andforty-three patients hospitalized with upper GI bleeding, 65.8% were male. The mean age of the patients was 68.6±11.56. The cut-off value for low and high De Ritis groups was selected as 1.57,which value seperated second tertile and third tertile of the patient population.İn hospital mortality rate was 13.1%. While albumin level was higher in the low De Ritis group, ALT, AST, and INR values were higher in the high De Ritis group. No statistically significant correlation was found between these two groups in terms of mortality. Moreover, De Ritis ratio did not show a significant difference between survivors and non-survivors (p=0.058). Conclusion: It was concluded that the rate of De Ritis is not an independent predictive factor for mortality in patients with upper GI bleeding. But, more prospective and randomized studies are needed to evaluate clearly the prognostic value of the De Ritis ratio in upper GI bleeding patients. Keywords: De Ritis ratio, aspartate aminotransaminase, alanineaminotransaminase, upper gastrointestinal bleeding, mortality

Association of Low Alanine Aminotransferase Values with Extubation Failure in Adult Critically Ill Patients: A Retrospective Cohort Study.

Background: Liberation from mechanical ventilation is a cardinal landmark during hospitalization of ventilated patients. Decreased muscle mass and sarcopenia are associated with a high risk of extubation failure. A low level of alanine aminotransferase (ALT) is a known biomarker of sarcopenia. This study aimed to determine whether low levels of ALT are associated with increased risk of extubation failure among critically ill patients. Methods: This was a retrospective single-center cohort study of mechanically ventilated patients undergoing their first extubation. The study’s outcome was extubation failure within 48 h and 7 days. Multivariable logistic and Cox regression were performed to determine whether ALT was an independent predictor of these outcomes. Results: The study included 329 patients with a median age of 62.4 years (IQR 48.1–71.2); 210 (63.8%) patients were at high risk for extubation failure. 66 (20.1%) and 83 (25.2%) failed the extubation attempt after 48 h and 7 days, respectively. Low ALT values were more common among patients requiring reintubation (80.3–61.5% vs. 58.6–58.9%, p < 0.002). Multivariable logistic regression analysis identified ALT as an independent predictor of extubation failure at 48 h and 7 days. ALT ≤ 21 IU/L had an adjusted hazard ratio (HR) of 2.41 (95% CI 1.31–4.42, p < 0.001) for extubation failure at 48 h and ALT ≤ 16 IU/L had adjusted HR of 1.94 (95% CI 1.25–3.02, p < 0.001) for failure after 7 days. Conclusions: Low ALT, an established biomarker of sarcopenia and frailty, is an independent risk factor for extubation failure among hospitalized patients. This simple laboratory parameter can be used as an effective adjunct predictor, along with other weaning parameters, and thereby facilitate the identification of high-risk patients.

Low ALT values amongst hospitalized patients are associated with increased risk of hypoglycemia and overall mortality: a retrospective, big-data analysis of 51 831 patients.

Sarcopenia and frailty influence clinical patients' outcomes. Low alanine aminotransferase (ALT) serum activity is a surrogate marker for sarcopenia and frailty. In-hospital hypoglycemia is associated, also with worse clinical outcomes. We evaluated the association between low ALT, risk of in-hospital hypoglycemia and subsequent mortality. This was a retrospective cohort analysis. We included patients hospitalized in a tertiary hospital between 2007 and 2019. Patients' data were retrieved from their electronic medical records. The cohort included 51 831 patients (average age 70.88). The rate of hypoglycemia was 10.8% (amongst diabetics 19.4% whereas in non-diabetics 8.3%). The rate of hypoglycemia was higher amongst patients with ALT < 10 IU/l in the whole cohort (14.3% vs. 10.4%, P < 0.001) as well as amongst diabetics (24.6% vs. 18.8%, P < 0.001). Both the overall and in-hospital mortality were higher in the low ALT group (57.7% vs. 39.1% P < 0.001 and 4.3% vs. 3.2%, P < 0.001). A propensity score matching, after which a regression model was performed, showed that patients with ALT levels < 10 IU/l had higher risk of overall mortality (HR = 1.21, CI 1.13-1.29, P < 0.001). Low ALT values amongst hospitalized patients are associated with increased risk of in-hospital hypoglycemia and overall mortality.

Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations

BackgroundCOPD exacerbations have negative impact on patients’ survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.MethodsThis is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.ResultsIncluded were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13–41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p < 0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6–3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08–3.1, p < 0.05).ConclusionsLow ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

Hepatitis B Surface Antigen Levels Are Related to Spontaneous Hepatitis B Surface Antigen Seroconversion in Inactive Hepatitis B Carriers.

The cure for hepatitis B is defined as the hepatitis B surface antigen (HBsAg) seroclearance and/or seroconversion. Predictors of spontaneous seroconversion are not well described. The objective of this study is to identify predictors of spontaneous HBsAg seroconversion from community practice. We performed a matched analysis of patients who HBsAg seroconverted (cases) and patients who did not HBsAg seroconvert (control) in a 1:5 ratio according to date of clinic visit between 2014 and 2019 in a large community practice situated in Los Angeles area. Baseline laboratory and clinical data were collected. Univariate analysis and 2-sided t tests were performed, χ test for proportions, and logistic regression. We identified 14 cases and 70 controls. The mean (±SD) ages of the cases and controls were 53.6 (±12.2) and 49.5 (±13.1), respectively (P=0.45). Most patients were women, and all patients were of Asian descent. There were statistically significant mean (±SD) baseline differences between cases and controls in HBsAg titers (459.8±311.0 and 782.0±393.3 IU/mL, P=0.01) and alanine aminotransferase (ALT) values (17.6±4.4 and 25.1±16.7 IU/mL, P<0.01), respectively. Baseline hepatitis B virus DNA and other pertinent laboratory values did not differ between cases and controls. Eleven of 14 cases (79%) and 11 of 70 controls (16%) baseline HBsAg titers were <1000 IU/mL (P<0.01). The results of a logistic regression demonstrated that HBsAg titers and ALT values were predictor variables for HBsAg seroconversion (P=0.01 and <0.01, respectively). Spontaneous HBsAg seroclearance and seroconversion is an uncommon event in patients with chronic hepatitis B. The most important predictors of seroconversion are HBsAg titers<1000 IU/mL and low baseline ALT values.

Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance.

Background: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. Methods: Patients’ clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. Results: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). Conclusion: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.

Low ALT blood levels are associated with lower baseline fitness amongst participants of a cardiac rehabilitation program

Background/ObjectiveObjective assessment tools for patients' frailty are lacking. Such tools would have been highly valuable for assessment of candidates for cardiac rehabilitation programs. Low ALT (Alanine aminotransferase) values were recently shown to be a promising parameter for objective, quantitative frailly assessment. MethodsThis was a retrospective study of patients participating in a cardiac rehabilitation program. ResultsPatients with lower ALT activity levels at the initiation of rehabilitation program had lower estimated METs values (6.86 vs. 7.73; p < 0.001), shorter stress test duration (06:41 vs. 07:44 min; p < 0.001), higher resting heart rate (72 ± 13 vs. 70 ± 13 BPM; p = 0.01) and lower heart rate reserve (49 ± 24 vs. 54 ± 24; p < 0.001). Multivariate linear modeling demonstrated that ALT values were Independent determinants of baseline exercise capacity (expressed in METs). ConclusionLower ALT values, measured prior to the initiation of cardiac rehabilitation programs may indicate frailty of patients and be indicative for poor rehabilitation outcomes. Further, prospective studies should assess the potential correlation between ALT values and rehabilitation efficiency. We aimed to assess the potential correlation between the baseline ALT values and the baseline exercise capacity, as expressed in METs (Metabolic equivalent of tasks). 3806 patients were included in our study.

External validation of the non-alcoholic fatty liver disease fibrosis score for assessing advanced fibrosis in Korean patients.

The degree of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) is a critical predictive factor for patient prognosis. This study was intended to perform external validation of the various fibrosis prediction models for assessing advanced fibrosis in Korean NAFLD patients. A retrospective study of 412 patients with NAFLD confirmed by liver biopsy in hospitals affiliated with the Koran NAFLD study group was conducted and the predictive ability of existing liver fibrosis prediction models including NAFLD fibrosis score (NFS), BARD, and fibrosis-4 were compared. Among 412 samples, 328 liver slides were suitable for evaluation. Advanced fibrosis was present in 60 (18.3%) of the patient samples. Univariate analysis found that the group with advanced fibrosis showed low alanine aminotransferase values and high aspartate aminotransferase/alanine aminotransferase ratios as well as a high incidence of diabetes. However, multivariate analysis showed that only the presence of diabetes and triglycerides was independent risk factors. The receiver operating characteristic was 0.64 in NFS, 0.58 in fibrosis-4, and 0.594 in the BARD model. The NFS was found to be the best at predicting advanced fibrosis among the three prediction models. The negative predictive value which predicts advanced fibrosis using the low cutoff (<-1.455) was high (86.6%). However, the positive predictive value which predicts advanced fibrosis using the high cutoff (>0.676) was 50.0% when we applied the NFS. Negative predictive value using the low cutoff value was high, but positive predictive value using the high cutoff value was low in a Korean NAFLD cohort using NFS.

Low ALT Levels Independently Associated with 22-Year All-Cause Mortality Among Coronary Heart Disease Patients.

Low alanine aminotransferase (ALT) blood levels are known to be associated with frailty and increased risk of long-term mortality in certain populations. However, the contribution of this marker to long-term outcome has not been assessed in patients with chronic coronary heart disease. The aim of the current study was to assess the association between low ALT values and long-term, 22.8-year, all-cause mortality in this population. We examined the association of low ALT (<17IU/l) with long-term all-cause mortality in the Bezafibrate Infarction Prevention (BIP) Registry population. Appropriate laboratory and survival data were available for 6,575 patients, without known liver pathology, included in the BIP registry, with a median follow-up period of 22.8years. The cumulative probability of all-cause mortality was significantly higher in the low ALT group compared with patients with higher ALT levels (65.6% vs. 58.4%; log-rank p < 0.001). Consistently, multivariate analysis, adjusted for multiple established predictors of mortality in this population, demonstrated that low ALT is independently associated with 11% greater long-term (22.8years) mortality risk [HR 1.11 (95% confidence interval: 1.03-1.19; adjusted p < 0.01)]. Low ALT levels are associated with increased long-term mortality among middle-aged patients with stable coronary heart disease. This association remained statistically significant after adjustment for other well-established risk factors for mortality in this population.

Characteristics of elderly hepatitis C virus‐associated hepatocellular carcinoma patients

The average age of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients has been rising in Japan. We evaluate characteristics of HCV-positive patients who develop HCC in older age to determine an optimal surveillance strategy. A total of 323 patients with three or more years of follow-up before HCC diagnosis and 323 propensity-matched controls without HCC were studied. HCC patients were classified into four groups according to age at the time of HCC diagnosis: group A (≤ 60 years, n = 36), group B (61-70 years, n = 115), group C (71-80 years, n = 143), and group D (> 80 years, n = 29). Clinical and laboratory data were compared. Platelet counts were significantly higher in the older groups at HCC diagnosis (P < 0.0001). The rate of platelet counts decline was lower in older groups (P = 0.0107). The average integration value of serum alanine aminotransferase (ALT) in groups A, B, C, and D were 80.9 IU/L, 62.3 IU/L, 59.0 IU/L, and 44.9 IU/L, respectively (P < 0.0001). In older patients (≥ 65 years old), cirrhosis and average integration value of ALT were significantly associated with hepatocarcinogenesis, but platelet count was not. Elderly HCV-positive patients (≥ 65 years old) with low ALT values developed HCC regardless of their platelet counts. These findings should be taken into account when designing the most suitable HCC surveillance protocol for this population.

Assessment of Clinical Utility of Low and High Normal Alanine Aminotransferase Values in Patients with Chronic Hepatitis B Virus Infection in Bangladesh

Background/Aims: There is a lack of consensus about the currently accepted range of normal values for serum alanine aminotransferase (ALT) levels because some investigators have claimed that the true values are significantly lower than those listed by kit manufacturers. Methods: A total of 255 chronic hepatitis-B-virus (HBV)-infected patients with traditional, normal levels of ALT (≤42 U/l) were divided into 2 groups: (1) low normal ALT (men: ≤30 U/l; women: ≤19 U/l) and (2) high normal ALT (men: 31–42 U/l; women: 20–42 U/l). The extent of hepatic inflammation and fibrosis was evaluated in these patients by examining liver biopsy specimens. Results: The levels of HBV DNA were >10,000 copies/ml in 58.4, 52.9 and 61.2% of the patients with traditional normal ALT, low normal ALT and high normal ALT values, respectively (p > 0.05). Also, the moderate degrees of hepatic necroinflammation [histological activity index (HAI)-NI score of ≧9] and severe hepatic fibrosis (HAI-F score of ≧3) were similar among the 3 groups of patients (p > 0.05). Conclusion: The newly defined low normal cutoff values for ALT did not exhibit any added clinical benefit for assessing the extent of liver damage in patients with chronic HBV infection in Bangladesh.

Role of lipid peroxidation as a mechanism of liver injury after acetaminophen overdose in mice.

Mitochondrial oxidant stress and peroxynitrite formation have been implicated in the pathophysiology of acetaminophen-induced (AAP-induced) liver injury. Therefore, we tested the hypothesis that lipid peroxidation (LPO) might be involved in the injury mechanism. Male C3Heb/FeJ mice fed a diet high in vitamin E (1 g d-alpha-tocopheryl acetate/kg diet) for 1 week had 6.7-fold higher hepatic tocopherol levels than animals on the control diet (8.2 +/- 0.1 nmol/g liver). Treatment of fasted mice with 300 mg/kg AAP caused centrilobular necrosis with high plasma alanine aminotransferase (ALT) activities at 6 h (3280 +/- 570 U/l) but no evidence of LPO (hepatic malondialdehyde, 4-hydroxynonenal). Animals on the vitamin E diet had similar injury and LPO as mice on the control diet. To verify a potential effect of the vitamin E diet on drug-induced liver injury, animals were pretreated with a combination of phorone, FeSO4, and allyl alcohol. We observed, 2 h after allyl alcohol, massive LPO and liver cell injury in the livers of animals on the control diet, as indicated by a 32-fold increase in malondialdehyde levels, extensive staining for 4-hydroxynonenal, and ALT activities of 2310 +/- 340 U/l. Animals on the vitamin E diet had 40% lower hepatic malondialdehyde levels and 85% lower ALT values. Similar results were obtained when animals were treated for 3 days with alpha- or gamma-tocopherol (0.19 mmol/kg, ip). Both treatments reduced LPO and injury after allyl alcohol but had no effect on AAP hepatotoxicity. Thus, despite the previously shown mitochondrial oxidant stress and peroxynitrite formation, LPO does not appear to be a critical event in AAP-induced hepatotoxicity.

A randomized, controlled trial of interferon alfa-2b alone and with simultaneous prednisone for the treatment of chronic hepatitis B

The aim of the study was to evaluate the safety and effectiveness of interferon alpha-2b with or without concomitant corticosteroid treatment in patients with chronic hepatitis B. Fifty-six patients were randomly allocated to two treatment groups. Group I (n = 25) received interferon alpha-2b (INTRON A, Schering-Plough Corporation) 5 million unit subcutaneously, three times a week for 24 weeks. Group II (n = 31) received interferon according to the same protocol and prednisolone in decreasing doses of 60, 40, 20 mg for 6 weeks. The two groups were well matched for demographic, biochemical, virological and histologic features. Both groups were followed up for 24 weeks after treatment. No statistical difference was observed between the two groups at the end of the follow-up in alanine aminotransferase values, HBV DNA negativation, HBeAg loss, anti-HBe seroconversion and the Knodell score. The greater proportion of HBsAg clearance in the combination group, particularly in patients with low alanine aminotransferase values, was, however, not significant. In patients with low alanine aminotransferase values, only the Knodell score was significantly decreased in patients treated with interferon and prednisolone. The only factor which was found to be a predictor of response was the assumed duration of hepatitis. These findings showed that a concomitant short administration of corticosteroids during the first weeks of interferon therapy did not improve results with interferon alone.