Mean Serum Alanine Aminotransferase Research Articles

Serum Alanine Aminotransferase may not be a good surrogate marker of Hepatitis C Virus infection: A Study of Blood Donors in University of Maiduguri Teaching Hospital (UMTH), Maiduguri, Nigeria

Background: Prior to the identification of Hepatitis C virus (HCV) in 1989, raised serum alanine aminotransferase (ALT) was used as a surrogate marker for non-A, non-B (NANB) hepatitis agents to reduce the risk of post-transfusion hepatitis. Most of this NANB hepatitis was later found to be due to HCV infection. The absence of a national screening policy for HCV infection and the non-availability of screening facilities in most of our health institution may place many blood recipients at risk of HCV infection. Aim: This study was set to evaluate the usefulness of serum ALT as a surrogate marker of HCV infection in blood donors. Methodology: The study was conducted at the University of Maiduguri Teaching Hospital between August 2002 to November 2002. Ninety-six healthy, volunteer, blood donors were screened for anti-HCV using a third-generation ELISA test kits, and all had serum ALT levels measured. Result: Antibodies against HCV was detected in 10.4% of donors and the overall mean serum ALT level was 8.84 (±5.6) iu/L. The mean serum ALT level for anti-HCV positive and negative was 7.7 (±2.45) and 8.9 (±5.86) iu/L, respectively, of which, there was no statistically significant difference between the two groups. Conclusion: While the prevalence of antibodies against HCV in blood donors appears to be high in north-eastern Nigeria, serum ALT levels may not be a good surrogate marker for HCV infection in blood donors in this environment. Key Words: Blood donors, HCV, Serum ALT levels. Sahel Medical Journal Vol.7(3) 2004: 88-91

AST/ALT Ratio In Acute, Uncomplicated Falciparum Malaria Infection: Comparison In Relation To The AST/ALT Ratios In Diseases Of The Liver

Introduction: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assayed in 110 adult patients (age range 18-40 years) presenting with acute, uncomplicated falciparum malaria infection and a control group of 80 age and sex-matched adults. Methods: Patient selection was done by simple random sampling of adult males and females presenting at the Bauchi State Specialist Hospital with a history of fever and malaise not lasting more that seven days and who were subsequently confirmed to be malaria-positive by microscopic examination of Giemsa-stained thin blood slides. Results: The mean serum AST and ALT activities were found to increase significantly relative to the AST and ALT values in the control group. Serum AST activity was 38.29 ± 1.37 IU in the falciparum malaria patients and 30.19 ± 1.37 IU in the healthy controls, p < 0.05. Similarly serum ALT activity was 31.06 ± 0.58 IU in falciparum malaria patients and 24.96 ± 0.92 IU in the control group, p < 0.05. The mean AST/ALT ratio in acute falciparum malaria infection was found to be 1.22 ± 0.14. This ratio differs significantly from the AST/ALT ratios reported for patients with Non-alcoholic steatohepatitis, chronic hepatitis C, alcoholic liver disease, hepatitis B and cirrhosis, p < 0.05. Conclusion:An AST/ALT ratio greater than 1 during acute falciparum infection contradicts earlier reports that the ratio is highly specific to cirrhosis alone or has application as marker of liver disease only. Therefore the application the AST/ALT ratio as a non-invasive means of assessing liver disease must be done with caution in the tropics where P. falciparum malaria infection is among the leading causes of hospital attendance.

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C†

The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P = .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed.

SEN virus infection among patients on maintenance hemodialysis in southern Taiwan

Objectives The prevalence and clinical significance of two SEN virus (SENV) strains, SENV-D and SENV-H, was investigated among patients on maintenance hemodialysis in southern Taiwan. Methods Sera from 99 uremic patients were tested for alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and SENV-D and -H DNA. Sera from 120 healthy blood donors were tested as a control group. Results Of the 99 patients, 24.2 and 7.1% were positive for anti-HCV and HBsAg, respectively, and the prevalence of SENV-D and/or -H (SENV-D/H), SENV-D and SENV-H DNA was 61.6, 46.5 and 27.3%, which was significantly higher than for donors (23.3, 18.3, and 5.8%, respectively; all P<0.0001). Patients with SENV-D DNA had significantly higher mean age among both patients ( P=0.019) and donors ( P=0.015). Mean serum ALT levels were significantly higher among patients with anti-HCV ( P=0.003) and patients with SENV-D and -H concurrent infection ( P=0.034). By multivariate analyses, the presence of serum anti-HCV and concurrent SENV-D and -H infection were independent factors associated with increased ALT level. Conclusions The prevalence of SENV-D/H infection is high among Taiwanese patients on maintenance hemodialysis with SENV-D more prevalent than SENV-H. The ALT level was associated with not only positive anti-HCV but also concomitant viremia of both SENV-D and SENV-H.

Racial differences in liver inflammation and fibrosis related to chronic hepatitis C

Background & Aims: Hepatitis C virus (HCV) infection is more prevalent in black compared with white Americans. However, the natural course of HCV in black patients has not been defined. Methods: We performed a retrospective comparison of initial liver tests, HCV genotype and viral load, and liver histology findings in 87 black and 136 white American chronic hepatitis C patients who were evaluated at the University of Maryland between 1995 and 1998. The liver biopsy examinations were interpreted by using the Knodell Histologic Activity Index (HAI) criteria. Results: Black HCV patients were older (46.3 vs. 43.3 yr; P = 0.004) and were more likely to be infected with HCV genotype 1 (95% vs. 75%). The modes of HCV transmission, estimated duration of HCV infection, and prevalence of alcohol abuse were similar in the 2 groups. Yet, black patients had lower mean total HAI scores (7.6 vs. 8.7; P = 0.021), periportal hepatocyte necrosis scores ( P = 0.021), and liver fibrosis scores ( P = 0.049). In keeping with less hepatic necroinflammatory activity, black patients had a lower mean serum alanine transaminase (ALT) level (85.5 vs. 122.7; P = 0.002). Black patients also had lower serum iron levels ( P = 0.009). There were no racial differences in the prevalence of increased iron studies and hepatic iron loading. Conclusions: Black chronic HCV patients have milder liver necroinflammation and fibrosis than white patients with similar HCV duration. These differences in liver histology were not explained by a variance in hepatic iron loading.

Efficacy of long-term dietary restriction of total calories, fat, iron, and protein in patients with chronic hepatitis C virus

Objectives A diet restrictive in total calories, fat, iron, and protein intake reduces serum alanine aminotransferase levels in patients with long-term hepatitis C virus infection. However, whether long-term dietary therapy causes adverse effects such as malnutrition and anemia due to a shortage of energy intake is not clear. We evaluated the balance of energy intake and changes in physical and hematologic indices of nutrition after a long-term dietary therapy. Methods Twenty-two patients with long-term hepatitis C virus infection that did not respond to or who were able or unwilling to take interferon therapy were enrolled in this study. Our prescriptions included 7 mg/d or less of iron, 30 kcal · kg −1 · d −1 of energy, 1.1 to 1.2 g · kg −1 · d −1 of protein, and a fat energy fraction of 20%. Patients were followed for 24 mo. Results Mean body fat percentage was 24.6% at entry and was significantly reduced after the diet prescription. Mean serum ferritin decreased significantly from 376 ng/mL at entry to 141 ng/mL after 24 mo. Mean serum alanine aminotransferase levels decreased significantly from 66 to 49 IU/L. Mean levels of hemoglobin, serum albumin, and cholinesterase did not change significantly during the follow-up period. Conclusions These results suggest that restriction of energy, fat, iron, and protein intakes is safely tolerated, so its long-term use should be recommended to patients with long-term infection with hepatitis C virus.

Salmonella bacteraemia in Turkish children: 37 cases seen in a university hospital between 1993 and 2002.

The aim of the study was to evaluate the clinical pattern of Salmonella bacteraemia in Turkish children. From 1993 to 2002, all children with a blood culture positive for Salmonella were retrospectively evaluated in the Division of Paediatric Infectious Diseases in Ankara University School of Medicine. All Salmonella isolates were serotyped and investigated for antimicrobial susceptibility. During the 10-year study period, 40 patients with Salmonella bacteraemia were identified. Of 37 eligible children, eight had enteric fever and 29 had non-typhoidal salmonellosis. Salmonella typhimurium was the most common serotype in the group with non-typhoidal salmonellosis. No significant differences were found between the enteric fever and non-typhoidal salmonellosis groups with regard to clinical features, laboratory findings and outcome, except in mean platelet counts and mean serum alanine aminotransferase (ALT) levels. In vitro resistance rates of Salmonella strains were low. Outcome was excellent in all but one child with hydrocephalus and gross neurological sequelae owing to meningitis. Salmonella bacteraemia is relatively uncommon in Turkish children. Differentiating between enteric fever and non-typhoidal Salmonella bacteraemia on clinical grounds is difficult.

Improved Nonalcoholic Steatohepatitis After 48 Weeks of Treatment With the Ppar–γ Ligand Rosiglitazone

Insulin resistance (IR) commonly is associated with nonalcoholic steatohepatitis (NASH). To establish whether IR causes NASH, this study was undertaken to determine if improving IR would improve the histologic features that define NASH. Thirty adults with prior biopsy evidence of NASH were enrolled to receive rosiglitazone, 4 mg twice daily for 48 weeks. All patients were overweight (body mass index [BMI] &gt; 25 kg/m2) and 23% were severely obese (BMI &gt; 35 kg/m2); 50% had impaired glucose tolerance or diabetes. Liver biopsy specimens were obtained before beginning treatment and at treatment completion. Twenty–six patients had posttreatment biopsies; of these, 22 had initial protocol liver biopsies that met published criteria for NASH on subsequent blinded evaluation. Within this initial NASH group, the mean global necroinflammatory score significantly improved with treatment and biopsies of 10 patients (45%) no longer met published criteria for NASH after treatment. Significant improvement in hepatocellular ballooning and zone 3 perisinusoidal fibrosis also occurred. Five patients withdrew early; the 25 patients completing 48 weeks of treatment had significantly improved insulin sensitivity and mean serum alanine aminotransferase (ALT) levels (104 initially, 42 U/L at the end of treatment). Adverse effects led to withdrawal of 3 patients (10%). Weight gain occurred in 67% of patients and the median weight increase was 7.3%. Within 6 months of completing treatment, liver enzyme levels had increased to near pretreatment levels. In conclusion, improving insulin sensitivity with rosiglitazone resulted in improved histologic markers of NASH, an observation suggesting that insulin resistance contributes to its development and that improving insulin sensitivity may be important in treating this liver disease.

Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone

Insulin resistance (IR) commonly is associated with nonalcoholic steatohepatitis (NASH). To establish whether IR causes NASH, this study was undertaken to determine if improving IR would improve the histologic features that define NASH. Thirty adults with prior biopsy evidence of NASH were enrolled to receive rosiglitazone, 4 mg twice daily for 48 weeks. All patients were overweight (body mass index [BMI] > 25 kg/m 2) and 23% were severely obese (BMI > 35 kg/m 2); 50% had impaired glucose tolerance or diabetes. Liver biopsy specimens were obtained before beginning treatment and at treatment completion. Twenty-six patients had posttreatment biopsies; of these, 22 had initial protocol liver biopsies that met published criteria for NASH on subsequent blinded evaluation. Within this initial NASH group, the mean global necroinflammatory score significantly improved with treatment and biopsies of 10 patients (45%) no longer met published criteria for NASH after treatment. Significant improvement in hepatocellular ballooning and zone 3 perisinusoidal fibrosis also occurred. Five patients withdrew early; the 25 patients completing 48 weeks of treatment had significantly improved insulin sensitivity and mean serum alanine aminotransferase (ALT) levels (104 initially, 42 U/L at the end of treatment). Adverse effects led to withdrawal of 3 patients (10%). Weight gain occurred in 67% of patients and the median weight increase was 7.3%. Within 6 months of completing treatment, liver enzyme levels had increased to near pretreatment levels. In conclusion, improving insulin sensitivity with rosiglitazone resulted in improved histologic markers of NASH, an observation suggesting that insulin resistance contributes to its development and that improving insulin sensitivity may be important in treating this liver disease. (H epatology 2003;38:1008-1017.)

Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children

Lamivudine is a new alternative therapeutic agent for chronic hepatitis B, in which alpha interferon (IFN-alpha) monotherapy is not successful enough. Published reports have revealed no satisfactory data on IFN-alpha and lamivudine combination therapy in children. The aim of this study is to investigate the efficacy and safety of this combination therapy in children with chronic hepatitis B. Children with chronic hepatitis B were given either IFN-alpha and lamuvidine (group 1, n = 47) or IFN-alpha alone (group 2, n = 30). Alpha interferon was administered as 5 million U/m2 s.c., thrice a week for 6 months and lamivudine 4 mg/kg per day p.o., maximum 100 mg, for 1 year. Clinical examination was performed; blood cell counts and serum alanine aminotransferase (ALT) and amylase were studied at each visit. At the third, sixth and twelfth month, serological markers were determined. End of therapy response was achieved in 19 (40.4%) patients in group 1 and in 14 (46.7%) children in group 2 (P > 0.05). In group 1, pretreatment serum ALT and hepatic activity index (HAI) were statistically higher in children who responded to therapy (P < 0.005). In group 2, mean serum ALT was higher and hepatitis B virus (HBV) DNA was lower in responders. Sustained response rate was 40.4 versus 43.3% in two groups. The response rate of IFN-alpha and lamivudine combination therapy in children with chronic hepatitis B was similar to that of IFN-alpha monotherapy. High ALT level and HAI, rather than low HBV-DNA level were found to be important predictors of response.

Treatment of chronic hepatitis D with thymus-derived polypeptide thymic humoral factor-gamma 2: a pilot study.

Thymic humoral factor-gamma 2 is a thymus-derived synthetic octapeptide, shown to be effective in chronic hepatitis B virus infection; as the latter is needed to support hepatitis D virus, thymic humoral factor-gamma 2 may have a therapeutic role in hepatitis D. To evaluate tolerability and efficacy of thymic humoral factor-gamma 2 in chronic hepatitis D. Intramuscular thymic humoral factor-gamma 2, 40 microg, was given for 15 consecutive days and twice weekly for 22 additional weeks to adult patients with chronic hepatitis D virus hepatitis. A total of 11 patients (male/female 9/2, mean age 45.9 years] completed the treatment period, 10 the 6-month follow-up. At baseline, hepatitis D virus-RNA was positive in 8/11 (73%) patients. During treatment, hepatitis D virus-RNA became undetectable in 3/8 (37%), decreased in 1/8 (13%), remained unchanged in 4/8 (50%) and persisted undetectable in 3 patients, negative at baseline. During follow-up hepatitis D-viraemia relapsed in all patients but 2, one already negative at baseline. No changes in hepatitis B virus markers occurred. Mean serum alanine aminotransferase levels did not change significantly None of the patients reached normal serum alanine aminotransferase levels. At the doses given, thymic humoral factor-gamma 2 has been of limited efficacy A possible role of thymic humoral factor-gamma 2 in the treatment of chronic hepatitis D requires further dose-finding studies and/or combination with other antivirals.

Relationship of TT virus infection with prevalence of hepatitis C virus infection and elevated alanine aminotransferase levels

A novel DNA virus, TT virus (TTV), was identified in a Japanese patient with posttransfusion hepatitis. The epidemiology and etiological role of this virus have not been elucidated. We investigated the epidemiology of TTV infection in hepatitis C virus (HCV) high endemic and low endemic areas, R town and M town, respectively. The seroprevalence, potential risk factors, and laboratory features of TTV in relation to those of HCV were analyzed. TTV DNA was detected using a seminested polymerase chain reaction and the TTV genotypes were determined by a direct sequencing method. TTV DNA was detected in 16.1% of the subjects in R town and 17.5% of those in M town. The TTV DNA positivity rates of the 2 areas did not differ significantly. A history of blood transfusion was not a specific risk factor for TTV infection. The mean serum alanine aminotransferase (ALT) level of the anti-HCV-positive subjects was significantly higher than that of the TTV DNA-positive subjects, most of whom had normal ALT levels. The TTV genotype distributions of these 2 distinct areas differed. These results suggest that TTV infection is widespread with a geographical genotypic distribution independent of HCV infection and that the ALT abnormalities are not attributable to TTV but to HCV infection in the general population.

Relationship of TT virus infection with prevalence of hepatitis C virus infection and elevated alanine aminotransferase levels

A novel DNA virus, TT virus (TTV), was identified in a Japanese patient with posttransfusion hepatitis. The epidemiology and etiological role of this virus have not been elucidated. We investigated the epidemiology of TTV infection in hepatitis C virus (HCV) high endemic and low endemic areas, R town and M town, respectively. The seroprevalence, potential risk factors, and laboratory features of TTV in relation to those of HCV were analyzed. TTV DNA was detected using a seminested polymerase chain reaction and the TTV genotypes were determined by a direct sequencing method. TTV DNA was detected in 16.1% of the subjects in R town and 17.5% of those in M town. The TTV DNA positivity rates of the 2 areas did not differ significantly. A history of blood transfusion was not a specific risk factor for TTV infection. The mean serum alanine aminotransferase (ALT) level of the anti-HCV-positive subjects was significantly higher than that of the TTV DNA-positive subjects, most of whom had normal ALT levels. The TTV genotype distributions of these 2 distinct areas differed. These results suggest that TTV infection is widespread with a geographical genotypic distribution independent of HCV infection and that the ALT abnormalities are not attributable to TTV but to HCV infection in the general population. J. Med. Virol. 58:235–238, 1999. © 1999 Wiley-Liss, Inc.

Efficacy and safety of simvastatin for high-risk hypercholesterolemia

Ten years′ experience of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk patients is reported. All patients started with 20 mg simvastatin/day. The simvastatin dose was increased to 40 mg in 22 patients. Fourteen patients needed further addition of cholestyramine. Simvastatin reduced plasma cholesterol by 33% after 1 month and was further reduced after adjustment of the lipid-lowering treatment. The mean reduction in plasma cholesterol varied between 30% and 35% in 2 to 10 years. Low-density lipoprotein cholesterol demonstrated mean reductions of 34% to 42%. Mean plasma triglycerides were reduced by 26% after 1 month and by 1% to 19% the following years. High-density lipoprotein (HDL) cholesterol increased initially by 8% and remained elevated at 7% to 11% during the first 6 years, but then dropped slightly below baseline. HDL 2 cholesterol increased by 9% to 25% the first 6 years and then decreased. HDL 3 cholesterol showed a persistent elevation during simvastatin treatment. About half of the subjects had minor transient but clinical insignificant increases in creatine kinase. No cases of myopathy were seen. Mean serum aspartate aminotransferase and alanine aminotransferase increased significantly but within the normal ranges during the 10 years. The tolerability and compliance of simvastatin treatment was excellent as judged from patients’ reports and from analyses of low-density lipoprotein cholesterol. This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long-term treatment of hypercholesterolemic patients at risk.

GB virus C/hepatitis G virus infection in patients on continuous ambulatory peritoneal dialysis.

GB virus C or hepatitis G virus (GBV-C/HGV) can be transmitted parenterally, very likely sharing common routes of transmission with hepatitis C virus (HCV). Patients on maintenance haemodialysis have been shown to be at increased risk of the novel GBV-C/HGV infection. Whether continuous ambulatory peritoneal dialysis (CAPD) can reduce the risk of GBV-C/HGV infection as demonstrated for HCV remains unknown. Serum GBV-C/HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) with nested primers derived from the 5'-untranslated region (5' UTR) of the viral genome. We investigated the prevalence of GBV-C/HGV viraemia in 60 patients on CAPD and the possible routes of transmission. One hundred healthy adults were selected as controls. The prevalence of GBV-C/HGV viraemia in CAPD patients was 23.3%, compared with 1% of healthy adults (P<0.05). Compared with patients without hepatitis B virus (HBV), HCV or GBV-C/HGV infection (n=39), those with GBV-C/HGV infection alone (n=11) have received more blood transfusions (mean 18.9 units vs 6.8 units, P<0.05). There were no significant differences between the viraemic and nonviraemic groups with respect to age, gender, duration of CAPD, duration of previous haemodialysis, previous history of surgery and co-infection with HBV or HCV. Three of the 11 (27.3%) patients with GBV-C/HGV infection alone had elevated serum alanine aminotransferase (ALT) level, and the frequency was significantly higher than that of patients negative for the viraemia (0%, P<0.05). In addition, the mean serum ALT level was also higher in the group with GBV-C/HGV infection compared with those without HBV, HCV and GBV-C/HGV infections (22.3+/-16.9 U/l vs 14.0+/-6.8 U/l, P<0.01). Patients on CAPD are at increased risk of GBV-C/HGV infection, and the risk parallels the number of previously transfused units of blood.

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients.

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.

Relationships between serum aminotransferase levels, liver histologies and virological status in patients with chronic hepatitis C in Taiwan.

In patients with chronic hepatitis C, the relationships between serum alanine aminotransferase (ALT) levels, histological liver injury and serum hepatitis C virus (HCV) RNA titres remain controversial. To evaluate these relationships, 93 Chinese patients with histological diagnosis of chronic hepatitis C were enrolled for this study. Serum ALT levels, HCV-RNA titres and HCV genotypes were examined. The histology was evaluated according to a modified histological activity score based on the degree of periportal necro-inflammation, intralobular necro-inflammation, portal inflammation, total necro-inflammation and fibrosis. The mean serum ALT level was significantly higher in patients with severe intralobular necro-inflammation activity than in patients with mild or no activity (P = 0.013). However, scores of intralobular activity were only weakly correlated with serum ALT levels (r = 0.27) and could not be used to adequately predict ALT values. Serum ALT levels showed no significant correlation with the scores of portal inflammation, periportal necro-inflammation, total necro-inflammation and fibrosis. Also, there was no significant difference in the mean serum ALT level among different serum HCV-RNA levels and HCV genotypes. Serum HCV-RNA titres and genotypes showed no significant correlation with liver histology and serum HCV-RNA titres were only weakly correlated with the total necro-inflammatory score (r = 0.27). In conclusion, although serum ALT levels were higher in patients with more severe intralobular necro-inflammatory activity, the correlation was not strong enough to adequately predict ALT values. Serum HCV-RNA titres and genotypes also showed no significant correlation with serum ALT levels and liver histologies.

Acetylcysteine Therapy for Chronic Hepatitis C

This trial reports the 6-month results of a pilot study using lymphoblastoid interferon alpha (IFNalpha) and acetylcysteine (N-acetylcysteine) separately and in combination in patients with chronic hepatitis C, genotype 1b, who were nonresponders to previous treatment with recombinant IFNalpha alone. 21 patients were randomly divided into three groups of seven each. Group A was treated with lymphoblastoid IFNalpha 6MU three times a week for 6 months; group B received the same schedule of lymphoblastoid IFNalpha as group A plus acetylcysteine 1200 mg/day per os in two administrations, and group C received only acetylcysteine 1200 mg/day per os in two administrations. Mean serum alanine aminotransferase (ALT) levels at 6 months in groups A and B, but not in group C, were significantly lower than baseline values (p < 0.05 and p < 0.03, respectively). Two patients in group A (28.6%) and three in group B (42.9%), but none in group C, had normalised ALT levels at 6 months. During follow-up, levels flared in one group A and in one group B patient. Thus, at the end of follow-up one group A and two group B patients were sustained responders. At the end of therapy and follow-up, hepatitis C virus (HCV)-RNA was negative in one patient in group A and two patients in group B. As no serious adverse effects were observed, therapy was never interrupted or suspended. Acetylcysteine alone had no effect on hepatic cytolysis and viral replication; lymphoblastoid IFNalpha showed a modest, but better, response than recombinant IFNalpha, and the combination therapy, although in a limited number of patients, appeared to be more efficient than lymphoblastoid IFNalpha alone.

Endoscopic Dilatation of Dominant Strictures in Primary Sclerosing Cholangitis

Background and Study Aims: In a subgroup of patients, primary sclerosing cholangitis (PSC) is complicated by high-grade focal strictures of the bile ducts, and this can have an unfavourable influence on the natural course of the disease. The aim of this study was to evaluate the efficacy and safety of endoscopic treatment in this selected patient group. Patients and Methods: Twelve symptomatic patients with primary sclerosing cholangitis and major ductal strictures were included in a prospective study of endoscopic treatment. All patients were managed by repeated angioplasty-type balloon dilation and nasobiliary catheter perfusion. A minimum of two treatment sessions was used, and therapy was continued until satisfactory reopening of the strictures was obtained. Routine endoscopic follow-up was performed after three, six, 12,18, and 24 months, and then at yearly intervals. The efficacy of therapy was assessed by evaluating clinical symptoms, laboratory data, and cholangiograms. Results: The long-term follow-up averaged 23 months (range: 12-50 months). Two to nine (mean:- three) treatment sessions were required to obtain satisfactory reopening of major biliary strictures. Eight patients showed considerable and sustained improvement. The mean serum bilirubin, alkaline phosphatase, γ-glutamyl-transpeptidase, and alanine aminotransferase levels fell significantly by 73% (P= 0.0164), 46% (P= 0.0022), 55% (P=0.0022), and 58% (P=0.0022), respectively. The average radiographic stricture score before treatment was 3.2 4-0.7 (mean 4-SD), and after treatment decreased to 1.9 4- 0.8 (P= 0.0033). Three patients required liver transplantation seven, 12, and 40 months after the initiation of endoscopic treatment, due to a deterioration in hepatic function or an inability to exclude complex biliary malignancy. No major procedure-related side effects were observed. Conclusions: Our results suggest that the endoscopic treatment of PSC patients with dominant bile duct strictures is effective, safe, and well-tolerated. However, it is important not to overlook the potential development of cholangiocarcinoma.

Therapeutic misadventures with acetaminophen: Hepatoxicity after multiple doses in children

We compiled reports of acetaminophen hepatotoxicity after multiple overdoses from published cases, cases reported to the Food and Drug Administration, and cases from Children's Hospital Medical Center, Cincinnati, Ohio. Forty-seven children (age range, 5 weeks to 10 years) received 60 to 420 mg/kg/day for 1 to 42 days; 52% had received adult preparations of acetaminophen. The mean peak serum aspartate aminotransferase level was 10,225 IU/L ( n = 45), and the mean serum alanine aminotransferase level was 7355 IU/L ( n = 31), which were significantly higher (both p < 0.001) than the mean serum aspartate aminotransferase level of 3500 IU/L and alanine aminotransferase level of 3098 IU/L found in children ( n = 12) with non-acetaminophen-associated hepatic failure. Serum acetaminophen levels for which an estimate of time from last dose could be calculated were available for 30 patients, of which 22 levels were greater than the toxic range described for acute ingestion. Twenty-four of 43 patients (55%) died, with an additional three surviving after orthotopic liver transplantation. Parents should be advised about the potential hepatotoxicity of acetaminophen when given to ill children in doses exceeding weight-based recommendations. (J Pediatr 1998;132:22-7)