OBJECTIVE:To determine whether isoform separation of carbohydrate-deficient transferrin (CDT) is of value in the diagnosis of alcoholic liver disease (ALD) and is specific to ALD when compared with other liver diseases.PATIENTS AND METHODS:During 1995 and 1996, 47 patients with ALD were evaluated with CDT at the Mayo Clinic in Rochester, Minn. The diagnosis of ALD was based on biochemical and histological analyses and on a history of drinking that exceeded 5 years with an average alcohol intake of more than 60 g/d. Disease controls included nonalcoholic steatohepatitis (NASH) (n = 26) and other liver disease (n = 22). Normal controls (n = 21) were healthy individuals without liver disease. Transferrin isoforms were quantified by densitometry of Coomassie-stained transferrins after affinity purification and isoelectric focusing. The pentasialo, tetrasialo, trisialo, disialo, monosialo, and asialo isoforms were quantified as percentages of total band densities.RESULTS:Receiver operating characteristic (ROC) curves were constructed for each isoform. The curves for total desialated isoforms (sum of disialo, monosialo, and asialo) displayed the best relationship between sensitivity and specificity with an ROC-area under the curve (AUC) of 0.922. The ROC-AUC values for individual transferrin isoforms in ALD vs NASH for pentasialo, tetrasialo, trisialo, disialo, monosialo, and asialo were 0.806, 0.917, 0.885, 0.933, 0.804, and 0.785, respectively. Only 58% of patients with ALD were detected at a specificity that excluded ALD in 84% of those who did not have it.CONCLUSION:Within alcohol ingestion times reported to us, no associations with recent drinking were observed. Alcohol as a cause of liver disease is not perfectly established by CDT analysis, although a high total CDT value favors ALD over NASH.

Liver biopsy remains an important diagnostic tool in the management of liver disease. Complications, though infrequent, are potentially disastrous. Risks and discomfort can be minimized with good technique, although prospective data to prove the superiority of one method over another are often lacking. Image direction is preferred in all cases, as is a transjugular approach when bleeding risks are judged to be high. Bleeding is essentially a random event. Outpatient liver biopsy is appropriate in almost every instance if immediate hospitalization facilities are available. It should be more widely practiced. Liver biopsies should only be done if, after thoughtful assessment, benefits are thought to exceed risks.

This document presents the official recommendations of the American Gastroenterological Association (AGA) on the evaluation and management of occult and obscure gastrointestinal bleeding. It was approved by the Clinical Practice and Practice Economics Committee on May 16, 1999, and by the AGA governing board on July 18, 1999.

Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non-progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non-progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.

Nonalcoholic steatohepatitis (NASH) is a reasonably well‐defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non‐progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non‐progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.

The risk of complications from percutaneous liver biopsy is low, but discomfort is common and complications require hospitalization in approximately 4% of patients. The optimal method of performing these biopsies is unknown. The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle. Between 1992 and 1994 836 patients were entered into a randomized study (489 in Rochester, MN; 347 in Barcelona, Spain). Patients were randomized immediately prior to liver biopsy into four groups: Trucut needle, or automatic biopsy needle, and with or without ultrasonography. Fisher's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications. The four biopsy groups were well-matched at entry with respect to age, sex, underlying liver disease, hemoglobin, prothrombin time, and platelet count. The use of ultrasound was associated with a decreased rate of hospitalization for pain, hypotension, or bleeding (2 vs. 9, P < .05). No difference in safety was found between the two types of needles. The number of passes needed to obtain specimens was similar for all four groups. The average length of the specimen was slightly greater with ultrasonographic-guided biopsies (1.7 mm vs. 1.6 mm, P < .05) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle (1.7 mm vs. 1.5 mm, P < .05), but this did not seem to be clinically important. The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy. The type of needle appears to offer little difference in safety or yield of diagnostic tissue, The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications. The value of this benefit must be weighed against the added cost of ultrasonographic guidance.

Non-alcohol-induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible Liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty-four patients received 13 to 15 mg/kg/d of UDCA for 12 months, Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months, Twenty-five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological. grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry, Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid-lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1-year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.

A 3-yr-old child underwent biopsy of a nonresectable liver cell adenoma. She was well thereafter, but at the age of 22 yr, she underwent orthotopic liver transplantation because the lesion had grown. The alpha-fetoprotein level was 4,300. The specimen showed poorly differentiated hepatocellular carcinoma in a noncirrhotic liver. At this writing, the patient is well 32 mo after transplantation.

Objectives.-To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests.Design.-A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia.Setting.-Communities, primary care centers, referral centers.Participants.-Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years.Interventions.-Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject.Main Outcome Measure.-Sensitivity of fecal blood tests for colorectal neoplasia.Results.-In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11 % by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant.Conclusions.-Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive.

A 63-year-old woman presented in May 1991 for evaluation of abdominal pain and fever.Her prior health had been excellent.She was American but had lived in Pakistan from 1957 to 1975, India from 1981 to 1982, and Egypt from 1989 to 1991.While abroad, she lived in developed areas, received recommended vaccines, and had no obvious infectious exposures.In February 1991, while living in Cairo, she developed upper abdominal pain, chills, night sweats, and recurrent fevers to 102'F.She had no diarrhea, jaundice, rash, joint pain, or pulmonary symptoms.Stool examination and a serological test showed no evidence of amebiasis, but Giardia lamblia was found in

To assess the contribution of fecal blood testing to cancer detection in a clinical practice setting, we studied records from 160 patients with both a new tissue diagnosis of colorectal adenocarcinoma and a preceding stool blood test (HemoQuant, Mayo Medical Laboratories, Rochester, Minn) determination. In this group, 71% had suggestive colorectal symptoms (particularly stool changes, overt bleeding, and abdominal pain) or anemia at presentation, and 29% were asymptomatic. Fecal blood levels remained normal in more than 40% of both symptomatic and asymptomatic patients. In only 26 patients (16% overall) was an abnormal fecal blood level the sole heralding feature, but this subset of patients had a more favorable stage. Fecal blood levels were higher with advanced, larger, and more proximal tumors and with stools collected before purgation. We conclude that, in the practice setting, fecal blood level elevation alone is an uncommon but important manner of colorectal cancer presentation, most cancers present with symptoms, and fecal blood levels are often normal in both symptomatic and asymptomatic patients.

The assumption that asymptomatic colorectal cancers bleed provides the rationale for widespread stool screening. The authors studied 12 patients with unoperated colorectal cancer but without colorectal symptoms and six healthy volunteers as laboratory controls. All stools were collected for 2 weeks and analyzed by the HemoQuant and Hemoccult tests. In controls, the mean HemoQuant value was 0.7 mg hemoglobin (Hb)/g stool (range, 0.1-1.8) and all stools were Hemoccult-negative. In cancer patients, the mean HemoQuant was 3.3 mg Hb/g (range, 0.3-13.2); stools were within the normal HemoQuant range (less than 2 mg Hb/g) in 38% and negative by Hemoccult in 70%. The mean cancer detection rate testing a single stool per patient was 57% for HemoQuant and 25% for Hemoccult (P less than 0.001). The detection rate rose testing multiple stools and was maximal with five stools at 83% for HemoQuant compared to 31% for Hemoccult (P less than 0.001). The authors conclude that fecal blood levels are commonly normal with asymptomatic colorectal cancer. Although higher with HemoQuant than Hemoccult, cancer detection rates by fecal blood testing appear to be lower than previously reported.

Nine thousand two hundred twelve liver biopsies were performed according to a defined protocol, and data were prospectively recorded to identify risk factors for major bleeding. There were 10 fatal and 22 nonfatal hemorrhages (0.11% and 0.24%, respectively). By comparison with a control group that did not hemorrhage, malignancy, age, sex, and the number of passes were the only predictable risk factors. The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4%; for nonfatal hemorrhage, 0.57%. In patients undergoing liver biopsy for nonmalignant disease, the risks are 0.04% and 0.16%, respectively.

Severe hepatic venous outflow obstruction and its manifestations often are recorded under the label "Budd-Chiari syndrome." Unfortunately, this label is ambiguous; it does not clearly identify the site of the lesion (hepatic veins versus inferior vena cava), its morphologic features (thrombotic versus nonthrombotic), or its cause. In the literature, implied or expressed definitions vary. Use of a standardized topographic and pathogenetic classification of hepatic venous outflow obstruction would enable investigators to group patients with comparable conditions, as required for therapeutic trials, prognostic evaluations, and studies of pathogenetic pathways. Review of our own cases revealed that hepatic venous outflow obstruction involving large hepatic veins is usually thrombotic and that isolated obstruction of the inferior vena cava or of small hepatic veins is usually nonthrombotic. Application of such a classification seems feasible and may yield useful results.