The utility of the 13C-galactose breath test as a measure of liver function.

BACKGROUND: The 13C-galactose breath test has been reported to be an accurate, non-invasive method for the assessment of liver function. AIMS: To determine the optimal doses of labelled and unlabelled carrier galactose necessary to perform the 13C-galactose breath test, to assess the utility of the 13C-galactose breath test in distinguishing between normal subjects and those with liver cirrhosis and to determine whether the 13C-galactose breath test can stratify patients with cirrhosis based on their Child-Pugh score. METHODS: Twenty-three control subjects and 30 patients with liver cirrhosis received fixed doses of unlabelled carrier galactose and labelled 13C-galactose. Breath samples were collected just before and at 30-min intervals up to 4 h after the ingestion of unlabelled carrier galactose and labelled 13C-galactose. Each sample was analysed for its 13CO2 content. RESULTS: Doses of 25 g/m2 of unlabelled carrier galactose and 100 mg of 13C-galactose had the greatest sensitivity (93%; 95% confidence interval, 76-99%) and specificity (87%; 95% confidence interval, 65-97%) for distinguishing between normal subjects and cirrhotics when the test was performed 2 h after ingestion. The 13C-galactose breath test was also able to distinguish between class A and class B or C cirrhotics. CONCLUSION: The 13C-galactose breath test is a useful non-invasive tool for distinguishing between healthy subjects and patients with liver cirrhosis and between cirrhotics with well-compensated liver disease and those with decompensated liver disease.

A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C non-responder to interferon monotherapy.

BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6-34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0-14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non-responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low.

Historical perspectives on the etiology of tuberculosis.

Robert Koch's 1882 demonstration that the tubercle bacillus was the true cause of tuberculosis established a new understanding of causation in medicine. This scientific breakthrough set in motion an etiological revolution with vast implications for the control of infectious disease, and its ramifications are still being felt today.

Outcome of de novo hepatitis C virus infection in heart transplant recipients.

The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 +/- 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P =.04) and high viral load at onset of acute liver disease (P =.02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P =.20). Development of ACH (P =.02) and MMF use (P =.0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.

Immunogenicity of hepatitis A vaccine in decompensated liver disease.

OBJECTIVE: Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepatitis A vaccine is recommended for patients with chronic liver disease. The aim of this study was to screen, immunize, and measure the safety and antibody response of the hepatitis A vaccine in liver failure and liver transplant patients. METHODS: This was a prospective immunization trial at a referral center for liver disease and liver transplantation. A total of 193 patients with severe chronic liver disease were screened and 24 patients were vaccinated. Sixteen end stage liver disease patients were compared with eight liver transplant patients. Hepatitis A vaccinations using 1440 ELISA units were given at 0 and 2 months. Serum hepatitis A antibody titers were measured after each vaccine dose. An antibody response > or = 33 mIU/ml was considered protective. RESULTS: Screening seropositive rate was 70 of 193 (36%) and 24 patients were available for vaccination. The median antibody titer was markedly lower in liver transplant patients, 0.0 mIU/ml compared to liver failure patients 34.7 mIU/ml (p < 0.001). Liver transplant recipients did not respond to the vaccine (0 of eight patients) compared with seven of 14 liver failure patients (seroconversion rate 50%, p = 0.02). CONCLUSIONS: Liver failure significantly reduces the antibody response to hepatitis A vaccine, and liver transplant recipients were unable to respond to the vaccine. Although this study was small, immunization should be considered early for susceptible patients with chronic liver disease because the development of liver failure may blunt the immunogenicity of the vaccine.

Listeria monocytogenes tricuspid valve endocarditis with septic pulmonary emboli in a liver transplant recipient.

Listeria monocytogenes has long been known as a pathogen of immunocompromised hosts, including solid organ and bone marrow transplant recipients. Its principal manifestations include bacteremia and meningitis. Endocarditis due to Listeria is far less common and in general affects the left side of the heart. We here report an unusual case of Listeria tricuspid valve endocarditis and septic pulmonary emboli in a sulfa-intolerant liver transplant recipient with a history of relapsing cytomegalovirus (CMV) hepatitis and an indwelling Hickman catheter. The literature on Listeria endocarditis and infections in transplant recipients is reviewed. The possible relationship between susceptibility to Listeria infection and the discontinuation of trimethoprim-sulfamethoxazole prophylaxis is of interest.

Pretreatment with methylprednisolone to prevent ERCP-induced pancreatitis: a randomized, multicenter, placebo-controlled clinical trial.

OBJECTIVE: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP). Uncontrolled data suggest a lower incidence of pancreatitis in patients with a history of iodine sensitivity when given pretreatment with corticosteroids. We conducted a clinical trial to assess the efficacy of a commonly prescribed corticosteroid, methylprednisolone, to prevent ERCP-induced pancreatitis. METHODS: Patients were entered into a randomized, multicenter, double-blind, placebo-controlled study of intravenous methylprednisolone (125 mg) versus a saline placebo immediately before the ERCP. All patients were evaluated for early and late complications. RESULTS: Two hundred eighty-six patients were randomized. Thirty-one randomized patients were excluded for technical reasons at the time of ERCP. Overall, the incidence of pancreatitis was 16 of 129 (12.4%, 95% CI: 6.7-18.1%) in the methylprednisolone group and 11 of 126 (8.7%, 95% CI: 4.4-15.1%) in the placebo group, which was not significantly different (p = 0.34). Although there was a higher rate of sphincterotomy performed in the methylprednisolone group compared to the control group (31.8% vs 16.8%, p = 0.005), the incidence of pancreatitis was not different when patients undergoing sphincterotomy were analyzed separately (13.6% in the methylprednisolone group and 9.6% in the placebo group,p = 0.50). There was no significant difference between the two groups for those with ERCP-induced pancreatitis in hospital length of stay (p = 0.22), days of parenteral analgesia (p = 0.09), or days of parenteral nutrition (p = 0.15). CONCLUSION: Intravenous methylprednisolone is not beneficial in preventing ERCP-induced pancreatitis.

A prospective, double-blind trial of somatostatin analog (octreotide) versus glucagon for the inhibition of small intestinal motility during endoscopic retrograde cholangiopancreatography.

BACKGROUND: Glucagon is effective when used as an antimotility agent during ERCP, but at high doses it may cause nausea and vomiting. Octreotide acetate, a long-acting synthetic analog of somatostatin, inhibits contractility of the small intestine and is generally well tolerated. The purpose of this study was to determine if octreotide given prior to ERCP reduced the requirement for glucagon and enhanced patient tolerance for the procedure. METHODS: Patients undergoing ERCP (n = 100) performed for a variety of indications (but not sphincter of Oddi manometry) were randomly assigned to receive normal saline solution or octreotide at a total dose of 25 micrograms, 50 micrograms, or 100 micrograms diluted in normal saline solution prior to the procedure. Glucagon was subsequently administered (as needed, to inhibit intestinal motility) by endoscopists who were blinded to the test substance given prior to the procedure. RESULTS: For all treatment groups, the dose of glucagon required to inhibit intestinal motility in patients who received octreotide prior to the procedure was not significantly different from the dose administered to patients who received normal saline solution. There was no significant difference in the incidence of nausea and vomiting when individual test groups were compared to the control group. CONCLUSION: Nausea and vomiting after ERCP were uncommon in all treatment groups. Administration of octreotide prior to ERCP did not significantly reduce the dose of glucagon required to inhibit intestinal motility. Tolerance for ERCP was similar for patients given octreotide when compared with those given glucagon to inhibit small intestinal motility.

The prevalence of coronary artery disease in liver transplant candidates over age 50.

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

Colectomy in patients with inflammatory bowel disease and primary sclerosing cholangitis.

PURPOSE: The aim of this study was to assess risk factors for early postoperative death in patients with primary sclerosing cholangitis who are undergoing colectomy. METHODS: The charts of 24 patients with primary sclerosing cholangitis who underwent colectomy between 1972 and 1990 at the Cleveland Clinic Foundation were reviewed. Clinical and laboratory data were collected and compiled to determine preoperative factors that might be helpful in predicting early postoperative death. RESULTS: The only factor that predicted a poor outcome was cirrhosis at the time of surgery. Three of 8 patients with cirrhosis and 0 of 16 patients without cirrhosis had an early postoperative death (P < 0.05, Fisher's exact test). CONCLUSION: We conclude that establishing whether or not patients with inflammatory bowel disease and primary sclerosing cholangitis have cirrhosis is helpful in determining the risk of colectomy.

Management of variceal bleeding in the 1990s.

BACKGROUND: Variceal bleeding is a common and serious problem. OBJECTIVE: To review the current management of patients with variceal bleeding. SUMMARY: Therapeutic options now include pharmacologic reduction of portal hypertension, endoscopic obliteration of varices, placement of decompressive shunts (both surgical and percutaneous), and liver transplantation. Each of these options may be required in different settings. A nonselective beta blocker can prophylactically reduce the risk of an initial bleed. Acute variceal bleeding is best managed by endoscopic sclerosis. Selection of therapy to prevent recurrent bleeding should be based on a full evaluation of the risk of bleeding and of liver failure. CONCLUSIONS: Successful management requires a multidisciplinary team, full patient evaluation, and selection of appropriate therapy.

Hemorrhagic ascites secondary to endometriosis.

Ascites secondary to endometriosis is extremely uncommon, but curable. We therefore report hemorrhagic ascites in a young woman with this disorder, and provide a literature review and summary of clinical features. The pathogenesis of ascites in this setting is unknown.

Effects of wheat, rice, corn, and soybean bran on 1,2-dimethylhydrazine-induced large bowel tumorigenesis in F344 rats.

This study was designed to determine the relative effects of four dietary brans on large bowel tumorigenesis in rats treated with 1,2-dimethylhydrazine (DMH). Four-week-old F344 rats were fed a 20% bran (either wheat, rice, corn, or soybean) semisynthetic diet or a no-fiber-added control diet for life. All rats except for one control diet for life. All rats except for one control group were infected with DMH (2SC doses; approximately 150 mg/kg body weight) at 8 and 10 weeks of age. Two additional groups were fed the control diet and then at 4 and 18 weeks, respectively, after the second DMH dose, were fed the wheat bran diet. All surviving rats were killed 9 months following the first DMH dose. Survival was increased in all groups receiving bran diets. Large bowel tumor incidences in the DMH group were as follows: control, 95%; wheat, 75%; rice 86%; corn, 100%; soybean, 84%; wheat after 4 weeks, 62% (lower than control group, p less than 0.05); wheat after 18 weeks, 84%. All but one of the DMH groups had approximately two tumors/tumor-positive rat; the corn group had four. The effect of bran on large bowel carcinogenesis appears to depend both on the source of bran and when it is fed in relation to tumor initiation.

Von Willebrand syndrome induced by a Bothrops venom factor: bioassay for venom coagglutinin.

Hereditary deficiency of the macromolecular Factor VIII complex results in classic von Willebrand disease in man and animals, a bleeder state characterized by loss of the multiple biologic activities associated with the Factor VIII complex, including the platelet-aggregating von Willebrand factor. The bleeding time is also long. Venom coagglutinin, a Bothrops factor that causes platelet aggregation in vitro, depletes the plasma of its von Willebrand factor. The rate of platelet aggregation is a function of the amount of the coagglutinin present. Based on this observation, a sensitive and quantitative assay for the venom coagglutinin was developed. We administered the purified Bothrops factor to normal pigs and dogs and induced a von Willebrand syndrome similar to the inherited disease. The plasma von Willebrand factor was severely depleted; the antihemophilic factor and the Factor VIII-related antigen were not depleted as much. The bleeding time was normal. During the induction phase of the syndrome, transient thrombocytopenia with a long bleeding time occurred. The pig was less sensitive than the dog to the effect of coagglutinin. The severity of the syndrome is determined by the amount of venom coagglutinin administered. It is suggested that the syndrome could be induced in any mammalian species because the plasma of all mammals tested in vitro is sensitive to the venom factor. This model provides another avenue for the study of the heterogeneity of the Factor VIII complex and the pathophysiology of its components.