The interaction of alcoholic liver disease and hepatitis C.

The following article reviews available data of the interaction of alcohol related liver disease and hepatitis C viral infection as well as special considerations for the treatment of these patients. Alcohol worsens the degree and accelerates the progression of hepatic injury, enhances the risk of developing hepatocellular carcinoma and decreases response to interferon therapy. Patients with hepatitis C should avoid alcohol ingestion.

A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults.

This study shows that two doses of a recombinant hepatitis B vaccine (10 micrograms or 20 micrograms of HBsAg per dose), administered 6 months apart to young, healthy adults, can induce an antibody (anti-HBs) response similar to that expected with the standard three-dose regimen of this vaccine given at intervals of 0, 1, and 6 months. While only 46-67% of the vaccinees displayed a protective anti-HBs titer of > or = 10 mIU ml-1 prior to the receipt of the second dose at 6 months, virtually all were primed as 97-99% of the subjects developed such a titer when tested a month after the second dose. Among vaccinees given 10 or 20 microgram doses, respectively, the secondary rise in antibody following the second dose yielded geometric mean titers (GMTs) of 1103 and 2538 mIU ml-1, respectively. The study further demonstrated that a two-dose regimen of vaccination induced strong immunologic memory for HBsAg, as a booster dose of vaccine given 2 years later resulted in a rapid and vigorous anamnestic antibody response.

Comparison of a rapid hepatitis B immunization schedule to the standard schedule for adults.

We report a prospective, randomized, single-blinded trial comparing immunogenicity of rapid (0, 1, and 2 months) versus standard schedule (0, 1, 6 months) hepatitis B vaccinations of healthy adults with recombinant hepatitis B vaccine (Engerix-B, 20 micrograms i.m.) (230 of 234) negative to hepatitis B were randomized and completed the study. Groups were similar in age, weight, race, and obesity rate, but the rapid schedule group had more women. Both groups reached > or = 100 mIU/mL at a similar rate, but a higher seroprotection rate at > or = 500 mIU/mL was reached by the standard schedule. No demographic variables influenced the effect of dose schedule on anti-hepatitis B titer. We conclude that rapid schedule vaccination gives a rate that is quicker than, and identical to, the rate of seroprotection of the standard schedule vaccination.

Pediatric rectal Dieulafoy's lesion.

Dieulafoy's lesions are an unusual cause of gastrointestinal hemorrhage. The overwhelming majority of lesions are found in the upper gastrointestinal tract, particularly along the lesser curvature of the stomach in the region supplied by the left gastric artery. Rectal Dieulafoy's lesions have never before been reported in the pediatric population, and our case represents only the third reported occurrence of a rectal Dieulafoy's lesion in the English medical literature. Successful treatment was administered, i.e., the combination of sclerotherapy followed by thermocoagulation. We therefore recommend that rectal Dieulafoy's lesion be included in the differential diagnosis of children with severe rectal bleeding and that management follow the same principles used to treat upper gastrointestinal tract Dieulafoy's lesions: injection therapy followed by heater probe coagulation.

Protein energy malnutrition in severe alcoholic hepatitis: diagnosis and response to treatment. The VA Cooperative Study Group #275.

BACKGROUND: Active nutrition therapy and the anabolic steroid oxandrolone (OX), in selected patients with severe alcoholic hepatitis, significantly improved liver status and survival. We report here on the changes in their nutritional parameters. METHODS: Protein energy malnutrition (PEM) was evaluated and expressed as percent of low normal in 271 patients initially, at 1 month and at 3 months. Active therapy consisted of OX plus a high caloric food supplement vs a matching placebo and a low calorie supplement. RESULTS: PEM was present in every patient; mean PEM score 60% of low normal. Most of the parameters improved significantly from baseline on standard care; the largest improvement seen in visceral proteins, the smallest in fat stores (skinfold thickness). Total PEM score significantly correlated with 6 month mortality (p = .0012). Using logistic regression analysis, creatinine height index, hand grip strength and total peripheral blood lymphocytes were the best risk factors for survival. When CD lymphocyte subsets replaced total lymphocyte counts in the equation, CD8 levels became a significant risk factor (p = .004). Active treatment produced significant risk factor (p = .004). Active treatment produced significant improvements in those parameters related to total body and muscle mass (ie, mid arm muscle area, p = .02; creatinine height index, p = .03; percent ideal body weight, p = .04). CONCLUSION: Deterioration in nutritional parameters is a significant risk factor for survival in severe patients with alcoholic hepatitis. This deterioration is reversible with standard hospital care. Active therapy further improves creatinine height index, mid arm muscle area and total lymphocyte counts. Hence, these later parameters appear to be the best indicators for follow-up assessments.

Helicobacter pylori is a risk factor for hepatic encephalopathy in acute alcoholic hepatitis: the ammonia hypothesis revisited. The Veterans Administration Cooperative Study Group No. 275.

OBJECTIVE: To determine whether infection with Helicobacter pylori is a risk factor for portosystemic encephalopathy in patients with acute, moderate or severe alcoholic hepatitis. DESIGN: Prospective, multicenter cohort study. SETTING: Eight Veterans Affairs Hospitals. PATIENTS: A cohort of 273 male patients enrolled in a Department of Veterans Affairs Cooperative Study performed to evaluate the efficacy of oxandrolone in combination with nutritional supplementation in moderate or severe alcoholic hepatitis. MEASUREMENTS: Admission serum IgG antibody titers against H. pylori by a specific and sensitive ELISA, demographic characteristics of patients, degree of protein calorie malnutrition, presence of ascites, bilirubin level, and known risk factors for hepatic encephalopathy (gastrointestinal bleeding, azotemia, hepatorenal syndrome, infection, and severity of disease); outcome was the presence of portosystemic encephalopathy. RESULTS: Of 188 patients with decompensated alcoholic hepatitis available for analysis, 117 (62.2%) had encephalopathy. Ninety-two (78.6%) of these were infected with H. pylori, compared with 62% of patients without encephalopathy (p = 0.013). In a step-wise regression model, H. pylori was an independent risk factor (relative risk: 2.4, 95% CI: 1.2-4.8) adjusting for ascites and protein-calorie malnutrition. CONCLUSIONS: Patients with acute, moderate or severe alcoholic hepatitis have a high H. pylori infection rate (as determined by serology), and those infected are at higher risk for portosystemic encephalopathy.

Increased plasma interleukin-8 concentrations in alcoholic hepatitis.

Patients with alcoholic hepatitis often have hepatic polymorphonuclear leukocyte infiltration and neutrophilia. Interleukin-8 is a cytokine that stimulates neutrophil chemotaxis and release of lysosomal enzymes. It is made by several types of cells, including fibroblasts, Kupffer cells and hepatocytes. In this study, serial plasma interleukin-8 concentrations were measured with enzyme-linked immunosorbent assay in 40 consecutive patients with moderate-to-severe alcoholic hepatitis over a 6-mo period. Two control groups included 10 patients without clinically important liver disease admitted for treatment of alcohol dependence and 12 healthy male volunteers. The mean plasma interleukin-8 level on admission was markedly increased: 695 +/- 146 pg/ml in the alcoholic hepatitis patients. The alcohol-dependent control group and the normal volunteer controls had mean interleukin-8 concentrations of 106 +/- 28 pg/ml and 10 +/- 5 pg/ml, respectively. Initially increased interleukin-8 levels in alcoholic hepatitis patients decreased to a mean of 182 +/- 42 pg/ml over the first month; levels had decreased further to 124 +/- 79 pg/ml after 6 mo. Increased interleukin-8 concentrations in patients with alcoholic hepatitis suggest a role for interleukin-8 in the neutrophilia and hepatic polymorphonuclear leukocyte infiltration of alcoholic hepatitis.

Bilateral photon deficient area along lateral abdominal wall in a Tc-99m DTPA renogram. A sign of massive ascites.

A patient with congestive heart failure and hepatic and renal dysfunction underwent Tc-99m DTPA renal scintigraphic studies in which persistent cardiac blood pool activity, hepatic arterialization, and a longitudinal photon deficient area in each side of the abdominal wall were observed. The increase in hepatic artery inflow was believed to be due to a decrease in portal inflow of the liver. The elevation of portal pressure secondary to heart failure is attributable to the decrease in portal inflow of the liver; this phenomenon could account for the hepatic arterialization. Progressive renal dysfunction with high body background resulted in demonstrable ascites as photon deficient areas. Scintigraphic findings of hepatic arterialization plus an abdominal photon deficient area reflect severe heart failure and renal dysfunction.

A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study.

A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen.