Insight into the negative effect and lipid profile alterations in liver of mice exposed to methylimidazolium ionic liquids, a novel "green" solvent.

Background: Ionic liquids (ILs) have been recognized as potential environmentally friendly solvents; however, their potential toxicity to living organisms warrants thorough investigation, particularly for novel-generation ILs in mammalian models. Methods: In this study, we examined the hepatic effects and disruption of lipid metabolism in mice exposed to 1-heptyl-3-methylimidazolium chloride (C7[MIM]Cl), a novel ILs. After four weeks of oral administration at different dosages (2.38, 5.95, and 11.9 mg/kg b.w.), we conducted clinical chemistry analysis and histopathological examination of the liver to assess biochemical and structural changes. Results: The low-dose C7[MIM]Cl group exhibited a significant increase in alanine aminotransferase (ALT) levels, while aspartate aminotransferase (AST) levels were elevated in both low-dose and high-dose groups without statistical significance. Histopathological examination showed inflammatory cell infiltration and red blood cell aggregation in the livers of mice exposed to C7[MIM]Cl, particularly in the high-dose group. Oxidative stress levels showed moderate changes in response to C7[MIM]Cl exposure. Notably, hepatic biochemical parameters revealed a dose-dependent increase in triglycerides (TG) levels with statistically significant differences compared to the control group (P ≤ 0.01). Targeted lipidomic analysis revealed notable alterations in liver lipids of mice exposed to C7[MIM]Cl, with lysophosphatidylethanolamine (18:0), phosphatidylcholines (18:0), and phosphatidylcholines (19:0) identified as critical lipids associated with C7[MIM]Cl exposure. Furthermore, metabolic pathway analyses demonstrated significant disturbances in the glycerophospholipid metabolic pathway. Conclusion: These findings provide valuable insights into the hepatic effects of C7[MIM]Cl exposure and novel perspectives on the disruption of lipid metabolism underlying ILs toxicity.

Three-Level Hepatotoxicity Prediction System Based on Adverse Hepatic Effects.

Hepatotoxicity is a major cause of drug withdrawal from the market. To reduce the drug attrition induced by hepatotoxicity, an accurate and efficient hepatotoxicity prediction system must be constructed. In the present study, we constructed a three-level hepatotoxicity prediction system based on different levels of adverse hepatic effects (AHEs) combined with machine learning, using (1) an end point, hepatotoxicity; (2) four hepatotoxicity severity degrees; and (3) specific AHEs. After collecting and curing 15 873 compound-AHE pairs associated with 2017 compounds and 403 AHEs, we constructed 27 models with three end point levels with the random forest algorithm, and obtained accuracies ranging from 67.0 to 78.2% and the area under receiver operating characteristic curves (AUCs) of 0.715-0.875. The 27 models were fully integrated into a tiered hepatotoxicity prediction system. The existence of hepatotoxicity existence, severity degree, and potential AHEs for a given compound could be inferred simultaneously and systematically. Thus, the tiered hepatotoxicity prediction system allows researchers to have significant confidence in confirming compound hepatotoxicity, analyzing hepatotoxicity from multiple perspectives, obtaining warnings for the potential hepatotoxicity severity, and even rapidly selecting the proper in vitro experiments for hepatotoxicity verification. We also applied three external sets (11 drugs or candidates that failed in clinical trials or were withdrawn from the market, the PharmGKB (offsides) database, and an herbal hepatotoxicity data set) to test and validate the prediction ability of our system. Furthermore, the hepatotoxicity prediction system was adapted into a flow framework based on the Konstanz Information Miner, which was made available for researchers.

Statins and its hepatic effects: Newer data, implications, and changing recommendations.

Hepatic adverse effects are one of the most commonly known adverse effects reported with statins. Frequently, fear of serious hepatic effects contributes to underutilization of statins as well as unnecessary discontinuation of its use among those indicated. There are changing data on the occurrence of these negative hepatic effects, recommendations on their actual risk, monitoring required, and safety of use in those with preexisting hepatic disorders. Based on reviewed literature, statins appear to be associated with a very low risk of true and serious liver injury. Unprecedented fears regarding hepatic adverse effects of statins among prescribers and patients can deny patients of the significant benefits of these agents. Routine periodic monitoring of liver function does not appear to detect or prevent serious liver injury and hence may not be indicated. But the potential of statins to cause significant and serious hepatic effects should not be overlooked in daily clinical practice. Statin use need not be avoided in patients with preexisting liver dysfunction such as nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, compensated cirrhosis, and compensated chronic liver disease if its use is clearly indicated. Physician's judgment based on the risk and benefit for an individual patient does matter when a strategy is chosen regarding the use of statins and monitoring patients while on statins.

Statin associated hepatic adverse effects: a retrospective review from a regional hospital in sultanate of oman.

OBJECTIVE: This study aimed at evaluating the prevalence, pattern and predisposing factors for hepatic adverse effects with statins in a regional hospital in Sultanate of Oman. METHODS: A retrospective review of the patient files in Department of Medicine during the year 2011 was done to evaluate any hepatic dysfunction possibly related to statins among the patients. For each case of suspected statin induced hepatic effect, additional details on temporal relationship, pattern of presentation, management, final outcome and any contributing factors were obtained. Difference in the occurrence of hepatic effects based on the patient demographics and drug characteristics was additionally evaluated. RESULTS: A total of 927 patients meeting the inclusion criteria were included for the study. Mean age of the evaluated patients was 63.1 ± 11.37 and median duration of use of statin in months was 22 (IQR, 43.25). In 40 (4%) of the 927 patients, there was presence of a hepatic effect considered to be statin related and only in 12 (1%) patients a significant transaminase rise (>3 times) was observed. Median duration of use of statin among those patients who developed suspected statin induced hepatic effects and those who did not was 45 (IQR,52) and 21 (IQR, 43) months, respectively and the difference observed was statistically significant. A significant difference in the prevalence of hepatic effects was observed only based on the duration of statin use. CONCLUSION: There was an infrequent occurrence of significant hepatic effects associated with statins in the study population. Our results support the latest recommendations including from United States Federal Drug Administration (US FDA) that statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of transaminases does not appear to detect or prevent serious liver injury in association with statins.

Neonatal cholestasis in Kashmiri children.

Neonatal cholestasis is prolonged elevation of conjugated serum bilirubin (more than 20% of total bilirubin) beyond first 14 days of life. After extensive evaluation a diagnosis of either biliary atresia or neonatal hepatitis is made in 70-80% of cases. Neonatal hepatitis and biliary atresia form a pathophysiologic process directed at various levels of the hepatobiliary tract. Inflammation in the bile duct epithelium may result in the sclerosis and obliteration of the bile ducts and manifest as biliary atresia. Primary hepatocellular inflammation is more likely to result in neonatal hepatitis. Half of the cases of neonatal hepatitis resolve without sequelae, while most of the biliary atresia cases require surgical intervention for repair or, ultimately, liver transplant.

Opportunistic hepatic infections in AIDS patients with fever of unknown origin.

The clinical features and histopathologic manifestations of hepatic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan remain unexplored. We report 28 AIDS patients (25 men, 3 women; mean age, 34 years) with fever of unknown origin who underwent 31 liver biopsies from December 1995 to May 1997. In most cases, the biochemical tests showed moderate to markedly elevated alkaline phosphatase concentrations, but normal or mildly elevated aminotransferase concentrations. The most common histopathologic finding was macrosteatosis, which was noted in 15 of the 28 patients. Another important histopathologic finding indicating the etiology of hepatic opportunistic infection was granuloma, which was found in 11 patients. Histochemical stain and culture of liver specimens yielded Mycobacterium avium complex (MAC) in eight patients, Mycobacterium tuberculosis in two patients, Histoplasma capsulatum in one patient, and cytomegalovirus in one patient with concomitant MAC infection. Therefore, a definitive diagnosis in AIDS patients with fever of unknown origin was made in 11 of the 28 cases with the assistance of liver biopsy. During follow-up, late extrahepatic involvement by the same infectious agents was found in six patients. Thus, hepatic manifestations could be a harbinger of disseminated opportunistic infections in AIDS patients.

PIP: AIDS patients are open to many opportunistic infections which often present as fever. The cases of 25 men and 3 women with AIDS of mean age 34 years, with fever of unknown origin who underwent 31 liver biopsies in Taiwan from December 1995 to May 1997, are presented. The biochemical tests most often showed moderate to markedly elevated alkaline phosphatase concentrations, but normal or mildly elevated aminotransferase concentrations. The most common histopathologic finding was macrosteatosis, noted in 15 of the 28 patients, while granuloma was found in 11 patients. The histochemical stain and culture of liver specimens yielded Mycobacterium avium complex (MAC) in 8 patients, Mycobacterium tuberculosis in 2 patients, Histoplasma capsulatum in 1 patient, and cytomegalovirus in 1 patient with concomitant MAC infection. A definitive diagnosis in AIDS patients with fever of unknown origin was therefore made in 11 of the 28 cases with the assistance of liver biopsy. During follow-up, late extrahepatic involvement by the same infectious agents was found in 6 patients. Hepatic manifestations could therefore be a harbinger of disseminated opportunistic infections in AIDS patients.

Chronic diseases and contraceptive use.

PIP: Barrier methods of contraception and natural family planning may pose unacceptable risks of unintended pregnancy for women with medical conditions in which pregnancy could be dangerous. Although more effective at preventing pregnancy, hormonal methods may affect the course of a chronic disease. The table that comprises this article outlines contraceptive choices and contraindications for women with the following diseases: breast cancer; endometrial, ovarian, and cervical cancer; deep venous thrombosis/pulmonary embolism; hypertension (past, moderate, or severe); diabetes (with and without vascular disease); liver disease; epilepsy; headache; and sickle cell disease.^ieng

Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a review of diagnosis and management.

Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a form of severe preeclampsia that threatens the gravida and her fetus. In this report, the diagnostic criteria and maternal and fetal risks of HELLP are defined. Prompt recognition and treatment in tertiary centers is emphasized, because the prognosis can be adversely affected by delayed or less than optimal diagnosis and treatment. Management guidelines are offered for treating this disorder. The potential roles of corticosteroids, plasmapheresis, and expectant management are critically evaluated. Subsequent pregnancy outcome, contraception, and preventative strategies are considered.

PIP: Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a form of severe preeclampsia which threatens the health and life of both pregnant women and their fetuses. Primary and consulting obstetricians therefore need to know how to recognize and treat the condition. The diagnostic criteria and maternal and fetal risks of HELLP are defined, with stress upon the prompt recognition and treatment of the condition in tertiary centers, because prognosis can be adversely affected by delayed or suboptimal diagnosis and treatment. Management guidelines are offered for treating the disorder, and the potential roles of corticosteroids, plasmapheresis, and expectant management are critically evaluated. Moreover, subsequent pregnancy outcome, contraception, and preventative strategies are considered.

Contraception in the patient with liver disease.

Selection of a method of contraception in patients with liver disease can be complicated. Tubal ligation should be considered in the setting of chronic liver disease for those patients who have completed families. Multiple reversible methods of contraception are currently available but may affect hepatic disease. Estrogen-containing contraceptive methods are contraindicated in patients with acute liver disease. Progestin contraceptives appear to be safe and multiple delivery systems are available. With rare exception, barrier methods and the intrauterine device may be offered as alternative methods.

PIP: Women with liver disease require careful contraceptive management. Of particular salience is the impact of sex steroids on liver function. If patients with chronic liver disease have completed their families, tubal ligation should be considered. Estrogen-containing oral contraceptives have been associated with cholestasis and development of hepatic adenoma and are contraindicated in women with acute liver disease. Progestin-containing hormonal methods appear to be safe, however. IUDs or barrier methods such as condoms and diaphragms can be selected, but they have lower efficacy rates.

Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol.

Anticonvulsants that induce hepatic metabolism increase clearance of oral contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not metabolized in humans and has little liability for causing metabolic-based drug-drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50 microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent gabapentin administration did not alter the steady-state pharmacokinetics of either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.

PIP: Anticonvulsants that induce hepatic metabolism increase the clearance of synthetic estrogens and progestogens used in oral contraceptives (OCs), thereby potentiating contraceptive failure. In contrast, the anticonvulsant drug gabapentin is not metabolized in humans and has little liability for metabolic-based drug interactions. The present study sought to confirm whether concurrent administration of gabapentin would alter the pharmacokinetics of norethindrone acetate (2.5 mg) and ethinyl estradiol (50 mcg) in healthy US women. A total of 13 women were enrolled for three menstrual cycles each. Pharmacokinetic values did not change appreciably as a result of the addition of gabapentin. The rate and extent of absorption of both hormones were unaffected by the anticonvulsant. Gabapentin plasma concentration time profiles and pharmacokinetic values from this study were similar to historical values after administration of gabapentin alone. The observed lack of interaction between gabapentin and norethindrone acetate or ethinyl estradiol is consistent with the fact that gabapentin is not metabolized, is not an inducer or inhibitor of hepatic drug metabolizing enzymes, is absorbed via a specific transport system for amino acids, and is not bound to plasma proteins. Anticonvulsant drugs that do not interact with OCs should be considered for the treatment of epileptic women of childbearing age who are using this method of fertility control.

A prospective review of laparoscopic cholecystectomy in Brunei.

Brunei has a small population and a unique medical setup: The number of laparoscopic cholecystectomies (LCs) performed in our institution represents the total number of cases performed in this country. A prospective analysis of all the LCs performed in Brunei is presented. All 220 LCs performed between February 1, 1992, and November 30, 1996, were prospectively recorded on a detailed protocol. Analyses were made with respect to preoperative patient demography, intraoperative complications, and postoperative morbidity and mortality. Symptomatic gallstone disease was found to be common among the ethnic Nepalese population. In this series, nine patients required conversion to open surgery (4%). Acute cholecystitis comprised 21% of cases, and the mean operating time was longer in these cases (144.1 min) than in elective cases (101.2 min; P = 0.002). The overall morbidity was 5% with one ductal injury (0.5%). The mortality rate in this series was 0.5%. Our results of LC are favorable and comparable with those of published series. We conclude that LC has been successfully introduced into our institution. This study also represents an unofficial audit of the state of development of LC in Brunei.

PIP: Laparoscopic cholecystectomy for the treatment of gallstone disease has the advantages of a shorter postoperative stay, more rapid overall recovery time, and better cosmesis compared to open cholecystectomy. To assess the state of development of laparoscopic cholecystectomy in Brunei, a prospective review of all 220 such procedures performed at the RIPAS Hospital in Bandar Seri Begawan in 1992-96 was conducted. These cases represent the total number of procedures performed in Brunei to date. The standard four-portal technique was used with an open Hasson trocar placed at the umbilicus. 81 patients (37%) were male and 139 (63%) were female; the mean age of patients was 46 years. Indications for the procedure included biliary colic (130 cases), acute cholecystitis (47 cases), and obstructive jaundice caused by gallstones (26). The mean operating time was 109 minutes. 9 patients (4%) required conversion to open surgery. The overall morbidity rate was 5%, with one ductal injury (0.5%). Gallbladder perforation with leakage of bile and/or gallstones occurred in 17% of cases. There was 1 death in this series (0.5% mortality), involving an 87-year-old woman with postoperative bronchopneumonia. 57% of patients did not require any form of analgesia in the postoperative period. The mean hospital stay was 3 days.

Hemorrhage caused by ruptured liver cell adenoma following long-term oral contraceptives: a case report.

A 41-year-old woman who had taken oral contraceptives for 14 years was admitted to the hospital with pain in the left shoulder region and epigastrium arising after regurgitation. Sonography and CT revealed a ruptured liver tumor with sealed-off liver hemorrhage. The resected specimen revealed a ruptured and partially necrotic liver cell adenoma. This paradigmatic case illustrates a rare but well known entity: liver cell adenomas prone to necrosis and hemorrhage, requiring emergency intervention, in women on long-term oral contraceptive therapy.

PIP: Over 70% of women with liver cell adenomas are oral contraceptive (OC) users, with an average duration of OC use of 5-10 years. In these women, liver cell adenomas are prone to necrosis and hemorrhage. This paper presents the case of a 41-year-old Austrian woman who presented with an intrahepatic and subcapsular hematoma, with a focal capsular tear sealed off by a clot and the diaphragm. Histology revealed a 4.5 cm, partially necrotic liver cell adenoma. The woman had been taking OCs for 14 years. Young OC users with epigastric disorders should be evaluated routinely by ultrasound for liver lesions and resection of liver lesions should be considered to control hemorrhage.

[Diagnosis of schistosomiasis]. / Diagnostic des schistosomoses.

PIP: Schistosomiasis affects around 200 million persons in the world despite improved knowledge of its epidemiology and physiopathology and significant therapeutic advances. Reliable diagnosis at present is based on observation of the parasite eggs. Schistosoma mansoni causes hepatointestinal schistosomiasis, and S. haematobium causes genitourinary disease. Other species are less frequently observed. The parasites develop in the intrahepatic blood vessels. The females migrate to different parts of the body to lay their eggs, still in the blood vessels. The eggs of different species are of variable size, but all contain a larva called miracidium and all possess a spur. Precise diagnosis is based on the morphologic characteristics of the eggs. As the eggs block different organs, especially the liver, they cause inflammatory granulomas to form. The different species of schistosomas have different geographic distributions that depend partly on the distribution of their mollusk intermediate hosts. S. mansoni and S. haematobium are present in Africa and S. mansoni is also found in the Americas. The eggs of S. haematobium are present most frequently in the urine, while in other species they are found in the stool. The procedure for collecting and preparing the specimens is described. Rectal biopsies obtained during consultations can be examined immediately if facilities are available, and biopsies may also be taken during surgical procedures. The size, color, shape, shell, and spur of eggs of each species are described, and characteristics peculiar to each are noted.^ieng

The contraceptive choice for a Wilson's disease patient with chronic liver disease.

Preserved fertility status is frequently encountered in patients with Wilson's disease, and contraceptive counseling may, therefore, be a relevant issue. Yet, several contraceptive methods can adversely influence the hepatic function, and the efficacy of others may be affected by the liver disease. We describe a patient with Wilson's disease manifested by cirrhosis, portal hypertension, and bleeding esophageal varices who underwent termination of pregnancy at 9 weeks' gestation. Following the procedure, contraceptive advice was sought in order to postpone conception until portal hypertension was controlled and hepatic function improved. Intramuscular depot medroxyprogesterone acetate was administered and tolerated well by the patient. A detailed discussion of the contraceptive options for patients with chronic liver disease, in general, and Wilson's disease, in particular, follows the case report.

PIP: Although the fertility status of women with Wilson's disease may be preserved, contraceptive method choice is complicated by the tendency for some methods to have an adverse effect on hepatic function and, conversely, for liver disease to compromise the efficacy of some contraceptives. This paper presents the case of a 28-year-old woman diagnosed with Wilson's disease at 13 years of age. She presented to an Israeli hospital at 9 weeks' gestational age with bleeding esophageal varices, cirrhosis, and portal hypertension. Although the patient had been oligomenorrheic, with menses every 2-3 months, she had experienced 3 spontaneous first-trimester abortions. Due to the urgent need for a portal decompression shunt procedure and the risk of further bleeding, the patient opted to terminate the current pregnancy. To prevent conception until the patient's liver condition stabilized, she was injected with Depo-Provera and penicillamine treatment was resumed. Although IUDs and estrogen-containing oral contraceptives are relatively contraindicated in women with liver dysfunction, spermicide and barrier contraceptives are highly recommended and progesterone-only preparations can be safely prescribed.

Seroprevalence of hepatitis E virus in an adult urban population from Burundi.

The prevalence of antibodies to the hepatitis E virus (HEV) was measured in a group of 129 adults from Bujumbura, Burundi, using an ELISA. The prevalence of anti-HEV IgG was 14%, much lower than that of hepatitis A virus (HAV) (97.7%). In addition to the lability of antibodies to HEV, this difference might be explained by the extensive availability of good-quality drinking water in the city. The presence of serologic markers of HBV (77.6%), HCV (27.1%), and human immunodeficiency virus (30.2%) was not associated with that of anti-HEV.

PIP: The seroprevalence of hepatitis E virus (HEV) was measured through use of data from a 1992-93 case-control study of patients with chronic liver diseases conducted at Kamenge University Hospital in Bujumbura, Burundi. 97.7% of subjects were anti-hepatitis A virus (HAV)-positive. In contrast, the seroprevalence of anti-HEV IgG was only 14%. Hepatitis B virus (HBV) markers were as follows: HBV surface antigen, 4.7%; antibody to HBV surface antigen, 55.8%; and antibody to HBV core antigen, 65.1%. The prevalence for all 3 HBV markers combined was 77.6%. No seropositivity was found for anti-hepatitis D virus among subjects positive for HBV surface antigen (4.7%) or for antibody to HBV core antigen (17.1%). 27.1% were anti-hepatitis C virus-positive. The prevalence of HIV was 30.2%. The presence of serologic markers of hepatitis A, B, and C virus was not associated with that of antibody to hepatitis E or HIV. Previous studies have found high rates of HEV in areas that have experienced high rainfall and flooding. The relatively low rate of HEV recorded in this study may reflect the fact that most Bujumbura residents use drinking water pumped from the middle of Lake Tanganyika and piped to taps near homes.

Spectrum of liver diseases in HIV infection.

BACKGROUND: Most earlier reports on the spectrum of liver diseases in HIV-infected individuals originated from the West. OBJECTIVE: To study the spectrum of liver diseases in HIV-infected individuals. METHODS: Seventy four consecutive HIV-positive patients (57 men; age range 23-75 years, mean 34) were studied prospectively with clinical evaluation, liver function tests, ultrasonography, radioisotope liver scan, markers of hepatitis B (HBV) and C (HCV) viruses, and liver histology whenever necessary. RESULTS: Thirty four patients (45%) were chronic alcoholics. Mean (SD) absolute lymphocyte count was 2521 (1271)/mm3; count < 2000/ mm3 was present in 20 patients. Serum bilirubin, transaminases and alkaline phosphatase levels were elevated in 13%, 13% and 24% of patients, respectively. Ultrasonography detected an abscess in two patients (tuberculous-1, amebic-1). Evidence of exposure to HBV was present in 81% (HBsAg-12, hepatitis B core and/or surface antibody-48); anti-HCV antibody was positive in 29.7%. Five patients with liver tuberculosis (granuloma-4, abscess-1) had AFB either in liver tissue or lymph nodes. CONCLUSION: Chronic alcoholism, HBV and HCV infection, hepatic tuberculosis, and evidence of other liver disease were common in patients with HIV infection.

PIP: A prospective study of 74 consecutive HIV patients (mean age, 34 years) at a public hospital in Mumbai, India, found evidence of hepatitis B and C virus, hepatic tuberculosis, and other liver disease. Clinical evaluation, liver function tests, ultrasonography, radioisotope liver scan, hepatitis B and C virus markers, and liver histology were performed. 34 patients (45%) were classified as chronic alcoholics on the basis of a history of consumption of at least 80 g of alcohol daily for at least 5 years and test findings. 59 (80%) had a history of multiple sex partners or encounters with commercial sex workers. 12 patients (16%) were hepatitis B surface antigen-positive and 22 (30%) were positive for hepatitis C virus antibody. Bilirubin, transaminases, and alkaline phosphatase were elevated in 13%, 13%, and 24%, respectively. Liver cirrhosis was present in 5 patients. Hepatitis B virus was detected in 4 patients and dual hepatitis B and C infection was found in another patient. Finally, 5 patients had liver tuberculosis. The mean absolute lymphocyte count was 2521/cu. mm; only 20 had a count indicative of immunosuppression (2000/cu. mm). These findings confirm that hepatic effects are a major feature of HIV infection in India.

Hepatitis C (HCV) genotype and viral titer distribution among Argentinean hemophilic patients in the presence or absence of human immunodeficiency virus (HIV) co-infection.

Hepatitis C (HCV) infection is frequent among hemophilic patients treated with non-inactivated factor-concentrates. Both HCV genotype and viral load have been suggested to be important prognostic markers of disease progression and treatment outcome. In addition, co-infection with the human immunodeficiency virus (HIV) has been associated with increased level of HCV replication and higher risk of developing liver failure. Thus, HCV genotype, viral load, and HIV co-infection are important factors in HCV infection. Using restriction fragment length polymorphism analysis (RFLP) and the branched-DNA (bDNA) assay, we retrospectively investigated the HCV genotypes and viral loads present in 59 Argentinean hemophiliacs, in the presence or absence of HIV infection. HCV genotype 1 was the predominant viral variant detected among HIV-negative (HIV-) (76%) and HIV-positive (HIV+) (82.5%) patients, followed by genotypes 3 (10.4%), 2 (2%) and a small proportion of multiply co-infected patients including genotypes 4 and 5 (6.25%). HIV+ patients had higher plasma HCV RNA levels than HIV- patients (88.4 +/- 16.5 x 10(5) Eq/ml vs. 24.7 +/- 10(5) Eq/ml) (P < 0.001); however, no correlation between HCV replication and level of immune suppression, evaluated by CD4+ T-cell measurement, was observed among HIV+ patients (r = 0.017). Abnormal and higher ALT levels were more frequently detected among HIV+ (93%; 123.6 +/- 15.7 U/liter) than HIV- (41%; 70.2 +/- 24.2 U/liter) patients (P < 0.001; P < 0.05). Although we were able to confirm previous reports suggesting the existence of increased HCV replication in HIV/HCV co-infected hemophiliacs, our data did not support the conclusion that HIV-induced immune suppression is directly responsible for this phenomena. It is possible that other factors induced by HIV are responsible for the increased levels in HCV replication observed.

PIP: Hepatitis C virus (HCV) infection is widespread among hemophiliacs treated with non-inactivated factor concentrates. The HCV genotypes and viral loads present in 59 hemophiliacs from Argentina were investigated through use of restriction fragment length polymorphism analysis and the branched DNA assay. 30 subjects were also infected with HIV. In both HIV-positive and HIV-negative hemophiliacs, HCV genotype 1 was the predominant viral variant (82.5% and 76%, respectively), followed by genotypes 3 and 2. HIV-positive hemophiliacs had significantly higher mean HCV viral loads than HIV-negative hemophiliacs; however, there was no association between HCV replication and the level of immune suppression as evaluated by CD4 T-cell measurement. Although HCV replication was increased in individuals co-infected with HCV and HIV, the data did not support the hypothesis that HIV-induced immune suppression is directly responsible for this finding. A study currently underway is investigating a possible correlation between infecting HCV genotype or pre-existing viral load and the severity of disease as assessed by liver histology or treatment outcome.

Combined oral contraceptives and liver disease.

Although some information is available about the risk of liver tumors associated with combined oral contraceptive use, little is known about the relationship with other hepatic problems. Data from two large long-term observational studies, the Royal College of General Practitioners (RCGP) Oral Contraception Study and the Oxford-Family Planning Association (Oxford-FPA) Study, were used to examine this issue. Observations accumulated over a period of up to 27 years were available for each study. The incidence of liver disease in each study was low. There was no evidence of an increased risk of serious liver disease overall among current or former pill users. The RCGP study found a modest increased risk of mild liver disease associated with oral contraceptive use which declined after four years of use and after cessation of use. This increased risk occurred in women who had used oral contraceptives containing more than 50 micrograms of estrogen.

[The effect of hormonal contraception on liver function]. / Vliv uzívání hormonální kontracepce na jaterní funkce.

PIP: Doing a liver test before the use of OCs is advisable for women who face risks, those with previous history of liver disease and familial benign hyperbilirubinemia. For those women who have a negative anamnesis with regard to each of these risk factors, it is not necessary to carry out a liver test before prescribing OCs. The risk of worsening latent chronic hepatitis is very small, and the occurrence of subsequent liver lesions is extremely rare. It is sufficient to carry out the test in women at risk after 3 months and after 1 year of OC use. This applies to patients with intensified cholestatic reactions, which have been asymptomatic, as well as to patients with latent chronic liver disease. The liver test needs to be repeated at regular intervals only when the following clinical symptoms are present: dyspepsia, pruritus, and icterus. Benign and malignant liver tumors cannot be confirmed by liver tests; therefore, there is no justification for this. On the other hand, it is believed that the very low incidence of liver tumors in a small group of women who continue to use OCs for more than 8 years would meet the indication for liver examination. Absolute contraindications for the use of OCs with regard to liver function are considered only for liver disease with prolonged higher liver test values, cholestatic jaundice in pregnancy, and liver tumor.^ieng

[Intestinal parasitosis and hepatic cirrhosis]. / Parasitoses intestinais e cirrose hepática.

The authors describe their experience, in a prospective survey, with the prevalence rates of intestinal parasites in patients with hepatic cirrhosis admitted to the Gastroenterology Unit of University Hospital of Federal University in Juiz de Fora, Brazil, whose fresh stools were examined by Hoffman-Pons-Janner, Baermann-Moraes and Willis methods. They compare the results of stool exams with two control groups and look for a relation with cirrhosis' etiology. A higher prevalence of some parasites was observed in cirrhosis than in people with other digestive diseases (group I). mainly for the Strongyloides stercoralis, found in 40.2%, chiefly in alcoholic cirrhosis. Oddly no one of the group I admitted in the same period had strongyloidiasis. Another group including all the people who had stool samples examined in the same period at the hospital had 1.91% of that helmintic infection (group II). A comparison is also made with the prevalence in schoolchildren between the ages of 7 and 14 studies eight years before (13.16%). Other parasites were also observed in different incidence between those with cirrhosis and the other groups and the results are presented. They conclude that hepatic cirrhosis must be included in the list of conditions which increases the risk of Strongyloides stercoralis infection.

PIP: In a prospective study conducted between July 1995 and June 1996 the prevalence of intestinal parasites is described in 35 (32 male, 3 female) patients with hepatic cirrhosis, aged 13-77 years, who had been admitted to the gastroenterology unit of the Federal University in Juiz de Fora, Brazil. The causes of cirrhosis were: alcohol (19 cases), hepatitis B virus (HBV) (3 cases), hepatitis C virus (HCV) (5 cases), HBV and HCV (2 cases), cryptogenetics (3 cases), Wilson's disease (1 case), biliary cirrhosis (1 case), and Gaucher's disease (1 case). Another 45 patients who were hospitalized during this period served as controls (Group I). Group II was comprised of 1411 persons who underwent parasitological tests during December 1995 and May 1996. Comparison was also made with 7371 tests performed in children aged 7-14 years who had been studied in 1988. Stools were examined by the Hoffman-Pons-Janner, Baermann-Moraes, and Willis methods. The results of stool exams were compared with those of the two control groups. A higher prevalence of some parasites was observed in cirrhosis patients than in patients with other digestive diseases (Group I). Of the 35 cirrhosis patients, 19 presented with positive parasite tests. Strongyloides stercoralis was found in 40.2%, chiefly in alcoholic cirrhosis patients, which was significant when compared to the other two control groups, but not significant when compared to the patients with nonalcoholic cirrhosis (4 cases of strongyloidiasis out of 16 patients). None of the 45 patients in Group I had strongyloidiasis. Group II (including all the people who had stool samples examined during the same period in the hospital) had a 1.91% rate of helminthic infection. A rate of 13.16% was found in the children's group.