Standardization of terminology of virological response in the treatment of chronic hepatitis C: panel recommendations.

The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard-of-care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing terms and definitions must be updated, standardized and/or redefined for easier interpretation of data and effective communication among clinicians. A panel of experts in HCV infection treatment met on 3 December 2009. Goals of the panel were to evaluate terms and definitions used traditionally in treatment with peginterferon and ribavirin, to refine and clarify definitions of existing terms that have varying meanings and to propose new terms and definitions appropriate for novel treatment paradigms emerging with development of new agents. A number of recommendations were accepted unanimously by the panel. Adoption of these terms would improve communication among investigators, enhance comparability among clinical trials, facilitate development of therapeutic guidelines and provide a standardized terminology for use in clinical practice.

Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response.

Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B (IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10(-17), poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients (P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients (P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of <35%. IL28B polymorphisms are the only common genetic variants associated with pretreatment LDL-C in G1-HCV. LDL-C remains significantly associated with SVR for heterozygous IL28B genotype patients, where LDL-C and HCV RNA burden may identify those patients with high or low likelihood of cure with pegIFN/RBV therapy.

Diffusion-weighted MRI of the transplanted liver.

AIM: To assess the value of diffusion-weighted imaging (DWI) in evaluating parenchymal disorders following orthotopic liver transplantation (OLT). MATERIALS AND METHODS: This institutional review board-approved, retrospective study measured the hepatic apparent diffusion coefficients (ADC) in patients following OLT. Those with vascular complications or within 3 months of OLT were excluded. A single-shot echoplanar sequence with b values of 50, 400 (or 500), and 800 s/mm(2) was performed. Liver biopsy specimens [performed with a median of 17 days after magnetic resonance imaging (MRI)] were recorded for the presence and severity of parenchymal disorders, such as acute cellular rejection, and recurrence of fibrosis in all patients, and the recurrence of viral hepatitis in patients with hepatitis C. ADC values were measured blinded to histology in 41 patients (33 males) who had 56 MRI scans. RESULTS: There was a significant difference in ADC values associated with a histological abnormality seen on core biopsy [n=43, mean (SD) ADC of 0.91 (0.15)×10(-3) mm(2)/s] and those associated with no histological abnormality [n=13, mean (SD) ADC of 1.11 (0.17)×10(-3) mm(2)/s; (p=0.003)]. ADC values did not predict any of the individual parenchymal disorders on logistic regression analysis. When the ADC value was <0.99×10(-3) mm(2)/s, there was a sensitivity and specificity of 85% and 72%, respectively, in predicting a parenchymal disorder (area under ROC curve=0.84; 95% CI 0.72 to 0.92). CONCLUSION: ADC measurements may help in deciding which patients require core liver biopsy after OLT. However, ADC values are not likely to be reliable in differentiating between the various parenchymal disorders.

Predictors of outcome in patients with unresectable hepatocellular carcinoma receiving transcatheter arterial chemoembolization.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been shown to improve survival in patients with unresectable hepatocellular carcinoma (HCC). AIM: To identify pretreatment factors that predicts increased mortality in HCC patients receiving TACE. METHODS: Retrospective review of all patients who underwent TACE for HCC from January 1999 to November 2004. Patient demographics, aetiology of liver disease, laboratory and imaging data regarding tumour characteristics were obtained. RESULTS: Eighty-eight patients (57 +/- 1 years age) received 1-4 sessions of TACE (1.4 +/- 0.1). Tumour size was 3.3 +/- 0.2 cm (range 1-13 cm, median 3 cm) with mean number of lesions 1.9 +/- 0.1 (range 1-7). Mean model for the end stage liver disease score: 11 +/- 0.4; cancer of the liver Italian program score: 1.3 +/- 0.1. Survival post-TACE (excluding those underwent orthotopic liver transplantation) was 12 +/- 0.3 months. By multivariate analysis, tumour size (HR = 1.37, 95% CI: 1.11-1.68, P = 0.003), hypovascularity (HR = 12.62, 95% CI: 1.79-88.92, P = 0.01) and elevated international normalized ratio (HR = 1.46, 95% CI: 1.10-1.92 P = 0.008) are shown to be significant risk factors for increased mortality. CONCLUSION: TACE therapy leads to a mean survival of 12 months in patients not receiving orthotopic liver transplantation. Tumour size, hypovascularity on imaging, and elevated international normalized ratio are predictors of increased mortality after TACE therapy for HCC.

All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

Simultaneous liver and pancreas transplantation in patients with cystic fibrosis.

BACKGROUND: Improved survival in patients with cystic fibrosis (CF) has led to an increased incidence of extrapulmonary complications of this disease. Of these, cirrhosis and pancreatic insufficiency, including CF-related diabetes (CFRD) and exocrine insufficiency, are significant causes of morbidity and mortality. Liver transplantation is the treatment of choice for cirrhosis in this setting, but the addition of an isolated simultaneous pancreas transplant in patients with CFRD has not been reported. METHODS: Two female patients with CF underwent simultaneous pancreas and liver transplantation. Both had pancreatic insufficiency, CFRD, cirrhosis, and preserved renal function. In each case, the liver and pancreas were procured from a single cadaveric donor. The liver transplant was performed first. A lower midline extension was added for improved exposure of the iliac vessels. The donor pancreas transplant was performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and early steroid withdrawal. RESULTS: Both patients recovered well with normal liver function, resolution of portal hypertension, and normal blood glucoses independent of insulin. As a result of the enteric exocrine drainage of the pancreas, they are now independent of supplemental pancreatic enzymes. CONCLUSIONS: Simultaneous liver and pancreas transplantation in CF patients provides the advantages of normalization of glucose and improved nutrition for patients requiring liver transplantation and should be considered in CF patients with CFRD who require liver transplants.

Induction of indoleamine 2,3-dioxygenase in vivo by IFN-con1.

Indoleamine 2,3-dioxygenase (IDO) activity as determined by increases in serum kynurenine was measured in a group of hepatitis C patients treated with consensus interferon (IFN-con1). Kynurenine levels increased significantly within 2 days of initiation of treatment but returned to normal values by week 4 after treatment. Although IDO is normally induced by IFN-gamma, no such IFN was detected by ELISA or biologic assays. Thus, consensus IFN induces low levels of IDO in vivo without an IFN-gamma intermediate.

Nonsteroidal anti-inflammatory drug-induced enteropathy: case discussion and review of the literature.

The adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract are well described. Evidence also shows that NSAIDs can be harmful to the small intestine. The use of NSAIDs has been associated with small intestinal strictures, ulcerations, perforations, diarrhea, and villous atrophy. Herein we present a case of NSAID-induced enteropathy with multiple diaphragm-like strictures that involved the distal 35 cm of ileum and review the literature of other cases of NSAID-induced enteropathy in which biopsy specimens were obtained for histologic analysis to rule out other causes. The prevalence of NSAID-induced enteropathy is unknown. Diagnosis can be made by endoscopy or at abdominal exploration. The role of radionuclide scans for diagnosis remains unclear. The pathogenesis is likely multifactorial. Mucosal diaphragms may be specific for NSAID-related disease. Treatment options for NSAID-induced enteropathy are discussed.

Acute hepatitis E by a new isolate acquired in the United States.

OBJECTIVE: To report the first case of acute hepatitis E by a novel isolate acquired in the United States and confirmed by nucleotide sequencing. MATERIAL AND METHODS: We describe the clinical manifestations and the results of associated laboratory studies in a man who was found to have acute hepatitis E infection. RESULTS: A 62-year-old man was hospitalized because of fever, abdominal pain, and jaundice. After an initial evaluation did not provide a cause, his serum was found to be positive for IgG anti-hepatitis E virus (HEV) by three antibody assays. Serum was also positive for HEV RNA by reverse transcriptase polymerase chain reaction (PCR). Sequencing results from the PCR products demonstrated substantial differences at the nucleotide level between this strain and the known Mexican and Burmese strains. CONCLUSION: On the basis of this initial report, HEV should be considered an etiologic agent in patients with acute non-ABC hepatitis in the United States.

Effect of food and food composition on alcohol elimination rates in healthy men and women.

Several studies have evaluated the effect of food on alcohol pharmacokinetics; however, most studies have used oral alcohol administration, which cannot separate the influence of food on absorption from its influence on alcohol elimination. Alcohol clamping uses intravenous alcohol and provides a direct measure of the alcohol elimination rate (AER). Two studies, using alcohol clamping at 50 mg %, were conducted to investigate the effect of food and food composition on AER (g/h) in healthymen and women. In the first study, 20 subjects underwent two clamping sessions, one after a 12-hour fast and another 1 hour after consuming a 530-calorie breakfast. In the second study, 8 subjects underwent four clamping sessions: one after a 12-hour fast and, in each of three "fed" sessions, 1 hour after a 550-calorie high-fat, high-protein, or high-carbohydrate breakfast. Comparison of AERs from the first study showed an average 25% increase following food compared to thatfollowingfasting. Men showed significantly higher AERs compared to women; however, the food effect was similar in both genders. In the second study, the AER showed a significant average 45% increase following the meal, regardless of composition, compared with that following fasting. These findings indicate that food intake results in increased alcohol elimination rates. The increase was similar for meals of different compositions, suggesting that the food effect is not due to specific interactions with meal constituents. Probable mechanisms for the increased alcohol elimination includefood-induced increases in hepatic blood flow and in the activity of alcohol-metabolizing enzymes.

Vaccination against hepatitis B in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: Most transplant centers in the United States immunize patients awaiting liver transplantation against hepatitis B to prevent acquisition of hepatitis B through transplantation (de novo hepatitis B). A recent study showed that only 16% of patients with cirrhosis awaiting liver transplantation responded to single-dose recombinant vaccine. METHODS: We studied the immunogenicity of double-dose recombinant vaccine in patients with cirrhosis awaiting liver transplantation. RESULTS: Over a 4-year period (January 1994 to December 1997), 140 patients with cirrhosis without past or current hepatitis B infection were given double-dose recombinant vaccine (40 microg of Engerix B; SmithKline Beecham, Philadelphia, PA) at 0, 1 to 2, and 2 to 4 months. Hepatitis B surface antibody (HBsAb) was measured 1 to 3 months after completing vaccination. The response rate was 37%. However, HBsAb titers became undetectable in 35% of the responders during the post-transplant follow-up period. One hundred and thirty-seven patients underwent 144 liver transplantation procedures during the study period, and 3 patients developed de novo hepatitis B (2.2%). Livers transplanted from hepatitis B core antibody (HBcAb)-positive donors was the source of de novo hepatitis B in all cases. Two of the 3 patients who developed de novo hepatitis B were immunized before transplantation and one of them was a responder. CONCLUSION: Although the response rate to double-dose recombinant vaccines is higher than the previously reported response to single-dose vaccine, it still is less than optimal.

The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites.

BACKGROUND: Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis. AIM: To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites. METHODS: All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume. RESULTS: A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25). CONCLUSIONS: Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites.

Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing. METHODS: A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh's Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/ fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity. RESULTS: Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10-42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively. CONCLUSIONS: SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.

Treatment of chronic hepatitis C in nonresponders to interferon monotherapy.

Sixty percent of patients fail to respond to interferon monotherapy. African-Americans with hepatitis C appear to respond less well to interferon monotherapy. Retreatment with a higher dose of consensus interferon for 48 weeks has led to a sustained virologic response rate of 13%. As a group, interferon nonresponders who breakthrough while on interferon monotherapy seem to have a more favorable response rate to a repeat course of treatment. Retreatment with interferon and ribavirin for 6 months in nonresponders led to a sustained virologic response rate of 21%. Preliminary results from two trials in the United States demonstrate similar treatment efficacy. There is now evidence that maintenance interferon therapy may also be beneficial in interferon monotherapy nonresponders.

Ethanol and human saliva: effect of chronic alcoholism on flow rate, composition, and epidermal growth factor.

Parotid saliva samples from 24 alcoholic subjects without evidence of cirrhosis were analyzed for changes in flow rate, composition, and epidermal growth factor (EGF) secretion. Mean (+/- SE) stimulated parotid saliva flow rate (ml/min/gland) was significantly (p less than 0.01) lower in alcoholic subjects than in matched control subjects. Reduction in parotid saliva flow rate was associated with significant (p less than 0.05) decrease in total protein and amylase secretion in this group of patients. In addition, secretion of immunoreactive EGF, a specific salivary protein, was also markedly reduced (p less than 0.05) in alcoholic patients. None of the parotid saliva samples from the alcoholic subjects had detectable bioactivity of EGF in saliva. These data suggest that chronic alcohol ingestion is associated with significant changes in parotid saliva secretion and its composition, which may perpetuate and compound ethanol-induced injury to the upper gastrointestinal tract.

Endoscopic esophageal manometry.

OBJECTIVE: We performed through-the-scope-manometry of the esophagus on 12 patients referred for esophageal symptoms. METHODS: A 3-lumen polyvinyl tube was passed through the biopsy channel of a standard video-endoscope. All patients underwent esophagogastroduodenoscopy with through-the-scope-manometry as well as a conventional laboratory-based manometric study; the sequence of the procedures was randomized. RESULTS: Mean lower esophageal sphincter pressure was 18 +/- 11 mm of mercury by both methods. In the lower esophagus, mean wave amplitude was 60 +/- 25 mm of mercury by through-the-scope manometry and 82 +/- 28 by laboratory testing. In the upper esophagus, mean wave amplitude was 50 +/- 26 mm of mercury by through-the-scope manometry and 63 +/- 20 by laboratory testing. Wave duration tended to be lower by through-the-scope manometry than by laboratory testing in the lower and upper esophagus. In nine patients with normal esophageal motility, 54% of swallows resulted in a peristaltic wave by the endoscopic study versus 100% for the laboratory test. CONCLUSION: Through-the-scope-manometry was able to accurately measure lower esophageal sphincter pressure compared with laboratory-based manometry. Peristaltic wave amplitude by through-the-scope manometry was reduced compared with laboratory-based manometry, most likely because of the use of dry swallows. Through-the-scope-manometry has promise as a screening test for esophageal motility disorders.

Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes.

Glycodeoxycholate (GDC) induces apoptosis in hepatocytes by a mechanism associated with DNA cleavage by endonucleases. In many models of apoptosis, proteolysis is required prior to DNA cleavage. Our aims were to determine if enhanced proteolysis is a mechanism causing GDC-mediated apoptosis. In cultured rat hepatocytes exposed to 50 microM GDC for 4 h, nonlysosomal proteolysis increased by 65% compared with controls. The serine protease inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK; 100 microM) reduced cell death from apoptosis by 75% after 4 h of treatment with GDC. TLCK also inhibited DNA fragmentation. There was a twofold increase in nuclear serinelike protease activity during GDC-induced apoptosis accompanied by a 2.5-fold reduction in nonnuclear serine protease activity, suggesting translocation of the protease from the cytosol to the nucleus. Zn2+, an inhibitor of apoptosis, also inhibited nonlysosomal proteolysis and nuclear serinelike protease activity. These novel data suggest that nonlysosomal serinelike protease activity contributes to hepatocyte apoptosis. These data may be important in understanding apoptosis in other cell types and in providing insight into the mechanisms of liver injury during cholestasis.

Measurement of liver volume using spiral CT and the curved line and cubic spline algorithms: reproducibility and interobserver variation.

BACKGROUND: The purpose of this article was to evaluate the accuracy and reproducibility of spiral computed tomography (CT) and the curved line and cubic spline algorithms in measuring liver volume. METHODS: Spiral CT was performed in phantoms, cadaveric liver specimens, and 35 live human subjects (19 healthy volunteers and 16 patients). Images were transferred to a workstation, and volumes were measured by two observers. One observer repeated the measurements at a separate sitting. RESULTS: The correlation between the CT measurement and the gold standard measurement of the cadaveric livers was very strong (r = 0.94). For the live human subjects, the intraobserver and interobserver correlations were extremely high (r = 0.999 and 0.997, respectively). The mean difference in liver volume measurements between the separate observations was 1%. CONCLUSION: The accuracy and reproducibility of this method of assessing liver volume are very high.

Screening for hepatocellular carcinoma in patients with advanced cirrhosis.

OBJECTIVE: Most available data on screening for hepatocellular carcinoma (HCC) in patients with cirrhosis originate from Asia and Europe. These data may not be applicable to patients from the United States because of geographic variation in the underlying etiology and other factors. Our aim was to assess the risk of HCC in U.S. patients with cirrhosis undergoing standardized screening. METHODS: All cirrhotic patients evaluated for liver transplantation at our institution from January 1, 1994-December 31, 1997 were included in this study. The screening strategy included initial screening, which was offered to all patients and consisted of alpha-fetoprotein (AFP), abdominal ultrasound, and computed tomography (CT) scan, and extended screening, which was performed only on transplant-eligible patients and consisted of semiannual AFP and ultrasound. RESULTS: During the study period, 285 patients with cirrhosis were evaluated for transplantation and underwent initial screening. Of these, 166 were eligible for transplantation and underwent extended screening during a median follow-up of 15 months (range 6-42 months). Twenty-seven HCC were found, 22 during initial screening and five during extended screening. The cancer-free proportions of the cohort who underwent extended screening at 1, 2, and 3.5 yr were 98.6% +/- 1.4%, 96.4 +/- 1.8%, and 77.1% +/- 1.7%, respectively (mean +/- SE). Hepatitis C, either alone or in part, was the etiology in 63% of patients with HCC. The sensitivity of CT scan (88%) was significantly higher than AFP >20 ng/ml (62%) and ultrasound (59%) for detecting HCC (p < 0.001). CONCLUSIONS: In patients with established cirrhosis, the risk of detecting HCC is maximal at the baseline screening (7%). Hepatitis C was the most common etiology for cirrhosis in study. In U.S. patients with established cirrhosis, CT scan exhibited higher sensitivity for detecting HCC than ultrasound or AFP.

Gender differences in alcohol metabolism: relationship to liver volume and effect of adjusting for body mass.

BACKGROUND & AIMS: Alcoholic liver disease purportedly develops more readily in women than in men. Some studies have demonstrated faster rates of alcohol elimination in women. This study examined whether gender differences in alcohol metabolism are related to differences in liver volume and/or differences in lean body mass. METHODS: Ten men and 10 women had alcohol elimination rates determined by clamping of the breath alcohol concentration at 50 mg/dL by means of a constant rate of intravenous infusion of 6% ethanol. Liver volume was determined by computed tomography. RESULTS: Mean alcohol elimination rate and mean computed liver volume were not significantly different in men and women. Lean body mass was 42% greater in men than in women. Consequently, the calculated alcohol elimination rate and liver volume per kilogram of lean body mass were 33% and 38% higher in women than in men, respectively. When the alcohol elimination rate was calculated per unit liver volume, no gender-related difference was found. CONCLUSIONS: Women have greater clearance of ethanol per unit lean body mass, confirming previous oral alcohol administration studies. Women have approximately the same liver volume as men, explaining the equivalent alcohol elimination rates seen when men and women are compared on the basis of liver size.