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ABSTRACT: The aim of this study was to determine if there is an association between non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS). NAFLD and PCOS are both known to be associated with metabolic syndrome/insulin resistance.
Fourteen consecutive female patients of reproductive age (20-45) either with liver biopsy proven NAFLD (50%) or abdominal ultrasound (US) consistent with steatosis together with elevated ALT levels (50%) were screened for PCOS using 2003 Rotterdam consensus meeting criteria. Other causes of hyperandrogenism were excluded. All subjects underwent relevant questionnaire and clinical exam together with hormonal assays, pelvic (1) or transvaginal US (13) and were screened for evidence of the metabolic syndrome.
Ten out of fourteen women matched 2003 Rotterdam consensus meeting diagnostic criteria for PCOS (71%). Eight women suffered from oligo/amenorrhoea, nine women manifested presence of hyperandrogenism and six had history of infertility. Seven women had evidence of biochemical hyperandrogenism with low SHBG, raised free testosterone and elevation of serum LH concentration. Seven women fulfilled US criteria for PCOS. Three of ten patients with PCOS also had type 2 diabetes mellitus. Women with PCOS and NAFLD had higher triglyceride and cholesterol and lower HDL level than group without PCOS. Five patients with NAFLD and PCOS had documented fibrosis on liver biopsy, indicative of more advanced liver disease.
Despite limitations of the study due to the sample size, we found evidence of PCOS in the majority of subjects with NAFLD. Women with NAFLD should be routinely screened for presence of PCOS, diabetes mellitus and metabolic risk factors for cardiovascular disease. Equally, women with PCOS should be screened for NAFLD. Evaluation for liver disease should be considered at an earlier age in some women with PCOS particularly those with an evidence of metabolic syndrome.
Journal of Gastroenterology and Hepatology 03/2009; 24(2):243-7. · 2.87 Impact Factor
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ABSTRACT: Serum concentrations of alpha-fetoprotein (AFP), variably elevated during liver injury, have been suggested to be of prognostic importance in acute liver failure (ALF), higher values being associated with improved outcome. Using a nephelometric assay, we measured AFP in sera obtained on admission from 206 patients prospectively enrolled in the US ALF Study, and on day 3 in 162 of these patients. The AFP ratio was defined as the day 3 AFP concentration divided by that observed on day 1. Median (range) admission serum AFP in all patients was 8.1 (1-1,811) ng/mL and increased to 17.6 (1.1-1,162) ng/mL on day 3 (P < 0.001). Higher absolute levels were not associated with improved outcome. In fact, admission AFP levels were lower in survivors not receiving transplants than in those who died or were transplanted (P < 0.001), whereas there was no difference between the 2 groups on day 3 (P = 0.34). However, a rise in AFP values between day 1 and day 3 indicated a better prognosis: the AFP ratio was 2.2 (0.11-22.1) in spontaneous survivors and 0.87 (0.11-16.4) in nonsurvivors (P < 0.001). An increasing AFP level indicated by an AFP ratio >or=1 was observed in 70 of 98 (71%) survivors, whereas a ratio <1 was observed in 51 of 64 (80%) nonsurvivors. In conclusion, AFP values change dynamically during ALF. In this large prospective study, higher absolute values of AFP did not predict a favorable outcome, but a rising level of AFP over the first 3 hospital days frequently indicated survival.
Liver Transplantation 12/2006; 12(12):1776-81. · 3.39 Impact Factor
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Anne M Larson,
Julie Polson,
Robert J Fontana,
Timothy J Davern,
Ezmina Lalani,
Linda S Hynan,
Joan S Reisch,
Frank V Schiødt, George Ostapowicz,
A Obaid Shakil,
William M Lee
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ABSTRACT: Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.
Hepatology 01/2006; 42(6):1364-72. · 11.66 Impact Factor
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Takeji Umemura,
Eiji Tanaka, George Ostapowicz,
Kevin E Brown,
Stefan Heringlake,
Nicolaos C Tassopoulos,
Richard Y-H Wang,
Anthony E T Yeo,
J Wai-Kuo Shih,
Koji Orii,
Neal S Young,
Angelos Hatzakis,
Michael P Manns,
William M Lee,
Kendo Kiyosawa,
Harvey J Alter
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ABSTRACT: SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects. SENV was detected in 54 (22%) of 248 patients with acute or chronic non-A-E hepatitis, 9 (35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 (24%) of 621 control subjects with liver disease and 76 (10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated.
The Journal of Infectious Diseases 12/2003; 188(10):1545-52. · 6.41 Impact Factor
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George Ostapowicz,
Robert J Fontana,
Frank V Schiødt,
Anne Larson,
Timothy J Davern,
Steven H B Han,
Timothy M McCashland,
A Obaid Shakil,
J Eileen Hay,
Linda Hynan,
Jeffrey S Crippin,
Andres T Blei,
Grace Samuel,
Joan Reisch,
William M Lee
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ABSTRACT: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition.
To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure.
Prospective cohort study.
17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group.
308 consecutive patients with acute liver failure, admitted over a 41-month period.
Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission.
73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not.
Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.
Annals of internal medicine 01/2003; 137(12):947-54. · 16.73 Impact Factor
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ABSTRACT: Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B. (HEPATOLOGY 2001;33:972-976.)
Hepatology 03/2001; 33(4):972 - 976. · 11.66 Impact Factor
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ABSTRACT: Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver-assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver-support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.
Journal of Gastroenterology and Hepatology 04/2000; 15(5):480 - 488. · 2.87 Impact Factor
