Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis.

BACKGROUND: Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature. AIM: To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. METHODS: One hundred and eighty-six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages. RESULTS: The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III-IV) had more fragments than those with no or mild fibrosis (stages 0-II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis. CONCLUSIONS: Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a liver disease that, until recently, has been underrecognized as a common cause of elevated liver enzymes. This distinct clinical entity is characterized by liver biopsy findings similar to those seen in alcoholic hepatitis but in the absence of alcohol consumption sufficient to cause such changes. Patients with NASH are often middle-aged and obese, with coexisting diabetes or hyperlipidemia, but NASH also occurs in younger lean, otherwise healthy individuals and even in children. Although NASH is generally a benign disorder, it may be progressive, leading to cirrhosis and complications of portal hypertension. Liver biopsy remains the gold standard for diagnosis. Therapy for NASH remains poorly defined, although weight reduction and ursodeoxycholic acid may have a beneficial effect.

Indications for and outcomes of cholecystectomy: a comparison of the pre and postlaparoscopic eras.

PURPOSE: Examine changing patient characteristics and surgical outcomes for patients undergoing cholecystectomy at five community hospitals in 1989 and 1993. PROCEDURES: In a retrospective chart review, data were gathered regarding gallstone disease severity, type of admission, patient age, number of comorbidities, American Society of Anesthesiologists (ASA) Physical Status Classification, length of stay, and multiple outcomes of surgery. MAIN FINDINGS: The volume of nonincidental cholecystectomies increased 26%, from 1611 in 1989 to 2031 in 1993. Nearly all of the increase occurred among patients with uncomplicated cholelithiasis and with elective admissions. In 1993, lengths of stay were significantly shorter and percentages of complications were significantly lower for infectious, cardiac, pulmonary, and gastrointestinal complications when controlling for patient case-mix characteristics. There were more major intraoperative complications (unintended wounds or injuries to the common bile duct, bowel, blood vessel(s), or other organs) in 1993. CONCLUSIONS: Different types of patients underwent cholecystectomy in 1993 compared with patients in 1989, which supports the hypothesis of changing thresholds. Statements supporting the safety of cholecystectomy in the laparoscopic era were borne out when controlling for differences in patient characteristics.

What predicts gastroenterologists' and surgeons' diagnosis and management of common bile duct stones?

BACKGROUND: Because the literature suggests numerous indicators of common bile duct stones, we undertook a systematic assessment of physicians' judgments of the clinical utility of eight indicators: patient age, history of jaundice, history of pancreatitis, levels of serum alanine aminotransferase, alkaline phosphatase, amylase, and total bilirubin, and common bile duct diameter on ultrasonography. METHODS: Random samples of 1500 gastroenterologists and 1500 surgeons were sent a survey asking them to indicate the importance of each potential indicator of common bile duct stones, the likelihood of common bile duct stones for each of nine clinical vignettes, and whether they would order a preoperative ERCP. An abbreviated survey was sent to nonrespondents. RESULTS: Although there was substantial variation in the importances assigned to each indicator, the most important indicators were serum total bilirubin and diameter of common bile duct on ultrasound. The best predictors of the decision to order an ERCP were perceived likelihood of stones and specialty. The average threshold for ordering an ERCP was 37%. Respondents did not differ from nonrespondents in the perceived importance of the eight indicators. CONCLUSIONS: The substantial variation among gastroenterologists and surgeons regarding the optimal approach to common bile duct stones has clinical implications. Patients will receive varying recommendations for care, depending on whom they see.

Mortality and complications associated with laparoscopic cholecystectomy. A meta-analysis.

OBJECTIVE: The purpose of this study was to perform a meta-analysis of large laparoscopic cholecystectomy case-series and compare results concerning complications, particularly bile duct injury, to those reported in open cholecystectomy case-series. SUMMARY BACKGROUND DATA: Since the introduction of laparoscopic cholecystectomy in the United States, hundreds of reports about the technique have been published, many including statements about the advantages of laparoscopic cholecystectomy compared with those of open cholecystectomy. There is an unevenness in scope and quality of the studies. Nevertheless, enough data have accumulated from large series to permit analyses of data regarding some of the most important issues. METHODS: Articles identified via a MEDLINE (the National Library of Medicine's computerized database) search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes of cholecystectomy were abstracted and summarized across studies. RESULTS: Outcomes of laparoscopic cholecystectomy are examined for 78,747 patients reported on in 98 studies and compared with outcomes of open cholecystectomy for 12,973 patients reported on in 28 studies. Laparoscopic cholecystectomy appears to have a higher common bile duct injury rate and a lower mortality rate. Estimated rates of other types of complications after laparoscopic cholecystectomy generally were low. Most conversions followed operative discoveries (e.g., dense adhesions) and were not the result of injury. CONCLUSIONS: There is wide variability in the amount and type of data reported within any single study, and patient populations may not be comparable across studies. Except for a higher common bile duct injury rate, laparoscopic cholecystectomy appears to be at least as safe a procedure as that of open cholecystectomy.

Predictors of common bile duct stones prior to cholecystectomy: a meta-analysis.

BACKGROUND: The decision of whether or not to investigate for common bile duct stones before cholecystectomy utilizes clinical, laboratory, and radiologic information (indicators). There is tremendous individual variation among clinicians in the criteria used for making this decision. Our aim was to perform a meta-analysis of published data to estimate the performance characteristics of the most commonly used preoperative indicators of common bile duct stones. METHODS: Using predetermined exclusion criteria, we selected articles from a MEDLINE search and bibliographic review. Weighted averages were used to determine summary sensitivity, specificity, and positive and negative likelihood ratios for each indicator for stones. RESULTS: From 2221 citations identified, 22 studies met inclusion criteria. The 10 indicators examined were reported in a common fashion in three or more articles, and could be assessed preoperatively. Seven exhibited a specificity greater than 90%. Indicators with positive likelihood ratios of 10 or above were cholangitis, preoperative jaundice, and ultrasound evidence of common bile duct stones. Positive likelihood ratios for dilated common bile duct on ultrasound, hyperbilirubinemia, and jaundice ranged from almost 4 to almost 7. Elevated levels of alkaline phosphatase, pancreatitis, cholecystitis, and hyperamylasemia exhibited positive likelihood ratios of less than 3. CONCLUSIONS: This meta-analysis has identified indicators for duct stones and ranked them according to likelihood ratios. These findings can be applied as guidelines for whether to investigate for duct stones before cholecystectomy.

Black pigment gallstones with cholesterol gallstones in the same gallbladder. 13 cases in a surgical series of 1226 patients with gallbladder stones.

We studied 1312 consecutive patients who underwent surgery for gallstones in the biliary tract at one university hospital in Siena, Italy, with a systematic classification of gallstones found within the gallbladder. Of these patients, 1226 were found to have gallbladder stones; 94 of these had black pigment gallstones. Of these, 13 patients were found to have black pigment gallstones and cholesterol gallstones within their gallbladder. They all had multiple black pigment gallstones, usually very small (all < 6 mm diameter), in association with larger cholesterol stones in the gallbladder lumen. The cholesterol gallstones were single in seven cases, double in two cases, and multiple in four cases. All 13 of these patients with black pigment stones in association with cholesterol stones had histologic evidence of either adenomyomatosis or Rokitansky-Aschoff sinuses in the gallbladder wall. In nine of the 13 patients, the black pigment stones were located both in the gallbladder lumen and in close association with the gallbladder wall (in areas of adenomyomatosis or in Rokitanski-Aschoff sinuses). In the other four patients, the stones were found in close association with the gallbladder wall alone and not freely mobile within the gallbladder lumen. It is concluded that cholesterol stones and black pigment stones may be found in the same gallbladder. This association is infrequent with an incidence of 13 of 1226 (1.06%) in our series. There appears to be some relationship between the formation of the black pigment stones and the presence of adenomyomatosis or Rokitanski-Aschoff sinuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin A hepatotoxicity: a cautionary note regarding 25,000 IU supplements.

Vitamin A hepatotoxicity has been reported at doses exceeding 50,000 IU/day. At 25,000 IU vitamin A per day, although elevated liver enzymes may be seen, hepatotoxicity is rare. We report a case of severe hepatotoxicity associated with the habitual daily ingestion of 25,000 IU of vitamin A bought as an over-the-counter dietary supplement. With the general availability of high-dose supplements and recent literature emphasizing the importance of vitamin A adequacy, the potential for vitamin A hepatotoxicity may increase. Health professionals should remain aware of the potential for vitamin A hepatotoxicity and elicit a vitamin A history in all patients being evaluated for liver dysfunction.

Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.

BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.

Ursodiol for hepatobiliary disorders.

PURPOSE: To explain the rationale supporting the use of ursodiol (ursodeoxycholic acid) for the treatment of patients with cholesterol gallstones and chronic liver diseases and to describe the results obtained in clinical trials. DATA SOURCES: Personal databases of the authors and MEDLINE were used to identify relevant English-language articles. STUDY SELECTION: Randomized controlled trials evaluating ursodiol for the treatment of patients with cholesterol gallstones and chronic liver diseases were emphasized. DATA SYNTHESIS: Ursodiol is at least as effective as chenodiol (chenodeoxycholic acid) for the dissolution of cholesterol gallstones and is associated with fewer adverse effects. Ursodiol desaturates bile, solubilizing cholesterol from the stone surface. The diameter of the largest stone is the most important determinant of successful dissolution. Dissolution with ursodiol is effective for approximately 30% to 50% of stones smaller than 20 mm in diameter, with the best results for small, buoyant stones. A meta-analysis of randomized trials with ursodiol found that the dissolution rate was 37% for patients treated with ursodiol at doses of more than 7 mg/kg per day or of more than 500 mg/d for at least 6 months. Maintenance therapy is effective for prevention of gallstone recurrence. Ursodiol also improves biochemical markers of cholestasis and inflammation when used to treat cholestatic liver diseases. By displacing potentially hepatotoxic bile salts, it appears to interrupt the cycle of cholestatic injury. It may also exert hepatoprotective membrane-stabilizing or immunomodulatory effects (or both). Improvements in laboratory variables are limited to the treatment period, with relapses after withdrawal of therapy. Pruritus may be markedly relieved in individual patients treated with ursodiol. CONCLUSIONS: Ursodiol is a safe and effective therapy for the treatment of patients with cholesterol gallstones. Although treatment with ursodiol leads to improvement in biochemical markers for cholestatic liver diseases, whether it alters the natural history of these disorders is the subject of ongoing trials.

Chronic hepatitis C. Advances in diagnostic testing and therapy.

The methods for diagnosing hepatitis C virus infection have been evolving since the first-generation enzyme-linked immunosorbent assay antibody test was devised in 1989. In addition to assaying for serum antibodies against viral proteins, serum and liver tissue can be tested for viral RNA, evidence of ongoing viral replication. The improving ability to diagnose hepatitis C has furthered the understanding of the natural history of this infection. Acute hepatitis C results in chronic elevations of serum transaminase levels following nearly one half of cases. Cirrhosis complicates approximately 20% of chronic infections. Long-standing chronic hepatitis C may play a role in the pathogenesis of hepatocellular carcinoma. Sustained normalization of serum transaminase levels, often accompanied by a decrease in or disappearance of viral RNA, occurs in approximately 25% of patients with chronic hepatitis C who are treated with a 6-month course of recombinant interferon alfa. This treatment can occasionally be complicated by hematologic, endocrinologic, and psychiatric adverse effects but is usually fairly well tolerated. Whether interferon therapy will diminish the risk of cirrhosis or carcinoma is not yet known. This article reviews the diagnosis of chronic hepatitis C infection as well as the mechanisms of action, efficacy, and adverse effects associated with interferon alfa therapy.

Improved results of extracorporeal shock wave lithotripsy with the Dornier MPL 9000 for single gallstones.

Our aim was to compare the results of extracorporeal shock wave lithotripsy with the Dornier MPL 9000 for patients with single radiolucent gallstones less than or equal to 20-mm diameter using higher power (kV) and more shock waves during lithotripsy with our results during the Dornier National Biliary Lithotripsy Study using lower power and fewer shock waves. Nineteen patients were treated at higher power (mean +/- SE, 21.0 +/- 0.4 kV) vs 11 patients at lower power (18.8 +/- 0.5 kV). In the higher power group, the actuarial rate for complete clearance of gallstone fragments was 39 +/- 9%, 63 +/- 9% and 78 +/- 9% after 6 weeks, 3- and 6-months follow-up, respectively, versus only 19 +/- 12% after 6 months in the lower power group. We conclude that the use of higher power and more shock waves during extracorporeal shock wave lithotripsy with the MPL 9000 results in fragment clearance rates over 6 months for patients with single gallstones that are significantly higher than those previously achieved in the Dornier National Biliary Lithotripsy Study.