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Biomedical subjects

C L Mendenhall

Publications and source records attributed to C L Mendenhall.

At least 19 recordsLinked to original sources
PubMed2001

Diagnostic status and treatment recommendations for Persian Gulf War Veterans with multiple nonspecific symptoms.

BACKGROUND: Unexplained symptoms have frequently been observed in deployed Persian Gulf War veterans (GWVs). Using factor analysis, the Centers for Disease Control and Prevention (CDC) has established criteria for Gulf War illness (GWI). We report here on the prevalence of GWI, identify comorbidities, and compare these with those of veterans without GWI. METHODS: GWVs who consented to complete questionnaires and laboratory measures were given complete physical and mental health examinations. Outcome measures included CDC criteria for GWI, the Medical Outcomes Study Short Form 36 (SF-36), clinical and laboratory evaluations, and structured psychiatric interviews. RESULTS: One hundred twenty GWVs were enrolled, and 89 received complete physical and mental health examinations; 83% met CDC criteria for GWI. Veterans with GWI (1) were older, (2) reported more combat exposure, (3) scored higher on measures of depression, post-traumatic stress disorder, and fibromyalgia, and (4) had poorer health-related quality of life. More than half had anxiety or depressive disorders, and 93% had at least one medical and/or psychiatric diagnosis. The SF-36 predicted mental health status with a positive predictive value of 81.58. By adding the Hamilton D rating for depression, the positive predictive value increased to 88.57. INTERPRETATION: The CDC criteria accurately identified GWVs negative for GWI. Most GWVs were positive for GWI. Neither CDC criteria nor CDC severity rankings distinguish between veterans with psychiatric syndromes and those without: both groups endorsed the same symptoms. More than half of those with GWI had a treatable anxiety or depressive disorder. The SF-36 was a valid predictor of mental health status, particularly when paired with the Hamilton depression interview.

Adult↗
PubMed1999

Cytokine response to BCG infection in alcohol-fed mice.

Alcoholics have increased susceptibility to infections including tuberculosis. Chronic alcohol treatment impairs host response to bovine mycobacterium infection from BCG. This study assesses the role of four cytokines (TNFalpha, IFNgamma, IL-4, and IL-10) in this impaired response. Twenty male C57BL/6 mice were pair-fed on the Lieber DiCarli control (LCD) or ethanol (LED) diets for 28 days. The LED treated subjects ate ad lib and consumed a mean of 13 g/kg/d of ethanol. After 14 days, based on body weight, subjects were randomly divided into four treatment groups of five each. Ten infected with 2x10(6) colony-forming units (CFU) of BCG by tail-vein. On day 28, the mice were sacrificed. Liver was cultured to determine the mycobacteria CFU/g tissue. Spleens were assayed for the levels of TNFalpha, IFNgamma, IL-4, and IL-10 mRNA relative to mRNA levels for a housekeeping gene using a quantitative reverse transcriptase PCR. Without BCG infection, only the mRNA for IFNgamma was increased by LED treatment, 51% (p = 0.0001). BCG infection significantly increased TNFalpha, IFNgamma, and IL-10 mRNA (p<0.0001). IL-4 mRNA decreased (p = 0.0006). Chronic LED plus BCG infection further increased TNFalpha (p = 0.002) and IFN-gamma (p = 0.04); IL-10 was unchanged, whereas IL-4 was marginally further decreased (p = 0.06). CFU/liver increased with LED (mean +/- SD, 72+/-33x10(5) vs. 39+/-17x10(5); p = 0.004). A significant direct correlation was observed between CFU and TNFalpha, r = 0.70, p = 0.03. In conclusion, BCG infection increases TNFalpha, IFNgamma, & IL-10 and decreases IL-4. CFU numbers correlate with mRNA for TNFalpha, and LED inhibits host containment of BCG infection as measured by liver CFU. This study could not identify cytokine alterations in either Th1- or Th2-type immune responses that might contribute to the impaired host response to the BCG infection.

Animals↗
PubMed1999

The antigenic heterogeneity of the bile duct epithelium in alcoholic liver disease. VA Cooperative Study Group 275.

The chronic alcoholic patient is usually immunosuppressed, but the significance of this phenomenon in terms of bile duct injury is unclear. The immunoreactivity of the bile duct cells was examined in a series of 69 frozen liver biopsy specimens obtained from patients with alcoholic liver disease, comprising 29 cases of cirrhosis, 26 of alcoholic hepatitis, 10 cases of alcoholic fatty liver, and 4 specimens from normal livers. Liver diseases such as primary biliary cirrhosis and human hepatic allograft rejection, known to have an autoimmune basis, share the characteristic feature of damage to the bile duct epithelial cells. In both instances the damage seems to be immune mediated, but the nature of the antigens involved is not established. We used the avidin-biotin-peroxidase complex method to test in alcoholic liver disease for the expression of a battery of surface antigen markers that have been incriminated in tissue injury and are usually present in lymphoid cells but also expressed by epithelium. In this study we investigated the expression of the following molecules: HLA class I (ABC) and class II (HLA-DR, HLA-DP, HLA-DQ), CD29, CD45RA, CD45RO, CD56, interleukin 1 (IL-I), IL-2, IL-4, interferon (IFN-gamma), tumor necrosis factor beta, and transforming growth factor beta1 (TGF-beta1). The bile duct epithelial cells strongly expressed HLA-ABC in all cases, CD56 in 47 of 55, IL-4 in 15 of 41, TGF-beta1 in 14 of 25, and CD29 in 4 of 25 cases. The other markers including IFN-gamma, HLA-DR, HLA-DP, and HLA-DQ were not expressed by bile duct cells. The expression of HLA class I agrees with previous observations while the absence of class II expression does not. The expression by the bile duct epithelium of CD56 confirms our own previous report. A new observation is the finding of molecules such as IL-4, TGF-beta1, and CD29 strongly expressed in the bile ducts cells. The presence of these molecules, taken together with the lack of IFN-gamma expression, contradicts previous speculations that attributed to IFN-gamma a role in the induction of major histocompatibility antigens and adhesion molecules in immune-mediated alcoholic liver disease.

Antibodies, Monoclonal↗
PubMed1998

Host response to mycobacterial infection in the alcoholic rat: male and female dimorphism.

Increased susceptibility to tuberculosis occurs in the alcoholic. One explanation for the altered susceptibility is a change in T-lymphocyte modulation. To evaluate this, 24 male and 24 female Sprague-Dawley rats were treated with either a Lieber-type liquid ethanol diet (LED) or an isocaloric control (LCD). After 2 weeks, half the subjects were infected with BCG (10(8) colony-forming units) and sacrificed after 42 days. Splenic helper (CD4) and suppressor/cytoxic (CD8) cells were quantitated by flow cytometry. By three-way analysis of variance, splenic cellularity was significantly increased by infection (p < 0.0001) but suppressed by LED (p = 0.0002). There was a marginal sexual difference (p = 0.065) with females exhibiting a 35% lower response while on alcohol. Examining lymphocyte subsets, the most significant changes were observed after infection (BCG) and alcohol treatment (LED). CD4 levels were diminished by LED (p = 0.0002) but markedly increased by infection (p < 0.0001), producing a highly significant interaction that affected both absolute number (p < 0.0001) and relative percent present (p = 0.0078). CD8 was influenced only by infection (p < 0.0001). This resulted in a infection-related increase in the CD4/CD8 ratio which was lower with LED (p = 0.0032). Splenic T-lymphocytes, predominately CD4, are involved in the host response to BCG hepatitis and are adversely influenced by LED, which may contribute to increased susceptibility.

Alcoholism↗
PubMed1997

Relationship between posttraumatic stress disorder and self-reported physical symptoms in Persian Gulf War veterans.

BACKGROUND: While prior studies show that combat veterans with posttraumatic stress disorder (PTSD) report more physical symptoms than veterans without PTSD, the link between PTSD and somatic complaints in Persian Gulf War veterans (PGWVs) is yet to be evaluated. METHODS: A questionnaire booklet was completed by 188 PGWVs, of whom half were patients in a veterans health screening clinic and half were non-treatment-seeking volunteers on active duty. The booklet included the Combat Exposure Scale, the Mississippi Post-Traumatic Stress Disorder Scale (MPTSD), and a subjective symptom-based health questionnaire. RESULTS: The 24 PGWVs (12.8%) with PTSD (MPTSD score > or = 116) reported more combat exposure (P = .02) and a greater number of physical symptoms (P = .001) than other PGWVs. Fatigue, nausea, muscle aches, dizziness, back pain, stomach ache, and numbness were much more likely to be reported by those with PTSD (MPTSD score > or = 116) than by those without PTSD (MPTSD score < or = 95). CONCLUSIONS: Physicians examining PGWVs should be alert to the possibility of PTSD in this group and that those with PTSD are more likely to report physical symptoms that may overlap with those in Persian Gulf syndrome. Consequently, mental health screening is essential, since for those veterans with PTSD diagnosis of other coexisting conditions may be confounded and early effective treatment of their PTSD may be delayed. Also, given the increased reporting of certain symptoms by those with PTSD, those seeking the cause of Persian Gulf syndrome should control for PTSD when determining the symptom cluster that may constitute this condition.

Adult↗
PubMed1997

I: the effects of recombinant human insulin-like growth factor-1 on nutritional recovery in the malnourished alcoholic rat.

BACKGROUND/AIMS: Alcoholics with severe liver disease (ALD) typically demonstrate the findings of protein calorie malnutrition. Such an occurrence might be anticipated with insulin-like growth factor-1 (IGF-1) deficiency. Furthermore, serum levels of IGF-1 are frequently very low in patients with alcoholic liver disease. The present study was undertaken to evaluate in an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1. METHODS: Controlled injury was induced by 14 days of calorie restriction and alcohol feeding (phase 1), which induced a 9% loss of body mass. Changes were compared with pair-fed, calorie-restricted controls that lost 7.8% of body mass and to unrestricted control rats that gained 28% above their pretreatment body mass during the same period. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1. RESULTS: Liver injury was minimal, but protein calorie malnutrition was moderately severe after phase 1 treatments. During recovery (phase 2), continuous consumption of alcohol--even in the presence of high calories and IGF-1 treatment--produced an incomplete nutritional recovery and, compared with normal rats, was associated with lower serum IGF-1 levels. The group treated with all three modalities (high calories, IGF-1, and abstinence from ethanol) had the most rapid and complete restoration of body weight. CONCLUSIONS: Recovery of nutritional status in the malnourished rat correlates significantly with serum IGF-1 levels. In the absence of ethanol and with sufficient caloric intake, IGF-1 treatment increased serum IGF-1 concentrations and accelerated nutritional recovery. Even with adequate calories, ethanol negated this recovery and was associated with lower serum IGF-1 concentrations. Further studies, both basic and clinical, are needed to better understand the mechanisms involved and to establish whether in patients with severe liver disease IGF-1 treatment would produce an accelerated improvement in nutritional status and improve both morbity and mortality. These animal studies suggest that this is the case.

Alcohol Drinking↗
PubMed1997

II: the effects of recombinant human insulin-like growth factor-1 on immunological recovery in the malnourished alcoholic rat.

BACKGROUND/AIMS: Immunological abnormalities are frequently observed in alcoholics with severe liver disease and are typically in association with immune abnormalities. Concomitantly, serum levels of insulin-like growth factor-1 (IGF-1) are frequently very low in these patients. Because IGF-1 is known to modulate both nutrition and immune status, the present study was undertaken to evaluate an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1. METHODS: Controlled injury was induced by 14 days of calorie restriction and alcohol feeding that resulted in a 9% loss of body mass. Changes were compared with normal unrestricted control rats that gained 28% above their pretreatment body mass during the same period. Immunological impairment was assessed using thymus and spleen mass, cellularity and spleen T-lymphocyte function. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1. RESULTS: The thymus was most severely affected, losing 52.3% of its mass and 55.7% of its cellularity. The spleen was diminished, losing 31.2% of its mass and 41.9% of its cellularity. All of the spleen T-lymphocyte subsets were diminished, with CD5 affected the least (37.1 %) and CD8 affected the most severely (51.7%). During recovery, only the group treated with high calorie intake, no alcohol intake, and IGF-1 (group 8) had complete restoration of all immunological parameters, including a recovery of T-lymphocyte function. Continuous consumption of alcohol, even in the presence of high calories and IGF-1, produced an incomplete recovery. CONCLUSIONS: Cessation of alcohol coupled with high calorie nutrition and IGF-1 treatment produced an accelerated improvement in host immunity. These animal studies suggest that IGF-1 is efficacious for this condition and supports the need for additional clinical studies.

Alcohol Drinking↗
PubMed1997

Effects of recombinant human insulin-like growth factor-1 and recombinant human growth hormone on anabolism and immunity in calorie-restricted alcoholic rats.

UNLABELLED: Patients with severe alcoholic liver injury exhibit very low serum insulin-like growth factor-1 (IGF-1) concentrations, along with many of the symptoms that might occur with an IGF-1 deficiency state (including severe protein calorie malnutrition and immunosuppression). This study was performed to assess the effects of recombinant human (rh) IGF-1 and/or rh growth hormone (rhGH) on anabolism and immunity in the calorie-restricted, immunosuppressed alcoholic rat. METHODS: Undernutrition was induced by calorie restriction such that each animal consumed 40% of ad libitum-fed controls. Alcohol was administered orally in the diet such that the mean daily intake was 9.4 g/kg/day. rhIGF-1 was administered by continuous subcutaneous infusion (380 micrograms/day) using a 14-day miniosmotic pump; rhGH was given by subcutaneous injections (400 micrograms/day). Matching placebo groups were also studied. RESULTS: On this regimen, ad libitum-fed controls were well nourished and increased body weight 34%, whereas Restricted controls lost 7.7% and Restricted alcohol-fed rats lost 15.2%. Significant but incomplete reversal of undernutrition was achieved with hormone therapy. Best improvement was obtained with combined therapy: rhIGF-1 + rhGH (p < 0.005; placebo versus active treatments). Immunologic impairment was observed to be severe in both thymus and spleen. The most severe changes were seen in thymi of the calorie-restricted, alcohol-fed rats, wherein 98% of the T lymphocytes were lost. rhIGF-1 treatment, but not rhGH, produced significant improvements in thymus. This was most pronounced in control rats (p < 0.005). Splenic T lymphocytes were less impaired and were more responsive to rhIGF-1 treatment; there was a maximum loss of 71% of T cells in Restricted, alcohol-fed rats. rhIGF-1 treatment completely restored splenic cellularity, as well as each of the T lymphocytes studied: CD5, CD4, and CD8. Functional status of splenic T lymphocytes was assessed by blast transformation after concanavalin A stimulation. Calorie restriction did not impair significantly this function in controls [Lieber-DeCarli control diet (LCD)]. However, it was significantly impaired in the Restricted, alcohol-fed rats (p = 0.003). In the presence of continued calorie restriction and alcohol, this function was not restored with either hormone (rhIGF-1 and/or rhGH). Their role in facilitating functional recovery after calories is restored, and alcohol is discontinued is under investigation.

Alcoholism↗
PubMed1997

A four-year review of patients with hepatitis C antibody in Department of Veterans Affairs facilities.

Hepatitis C virus [HCV] has recently been recognized as an emerging pathogen of surprising proportions. The clinical liver illness associated with HCV infection can be minimal or none, but in a notable number of persons it can ultimately cause debilitating chronic liver disease, fibrosis, cirrhosis, and hepatic failure, and it is likely related to an increased incidence of hepatocellular carcinoma. From 1991 to 1994, an annual electronic census was sent to 168 Veterans Health Administration facilities requesting serologic data on HCV in patients seen in Department of Veterans Affairs facilities. Response rate to the mandatory survey was 100%. In 1991, 6,612 individual patients were reported as positive for HCV antibody in the Department of Veterans Affairs system. This increased yearly from 1992 to 1994 with 8,365, 14,097, and finally 18,854 persons, respectively. This represents an increase of more than 285% during the 4-year period. Increases in HCV antibody for the same period were seen in all major regions of the United States and in the specified large metropolitan areas. In the New York area and in coastal California, this trend of new case identification may have plateaued during 1993 and 1994. Overall, total patients seen nationally in the Veterans Health Administration increased by only 4.87% during the same period, 1991 to 1994. Thus, the increase in persons positive for HCV antibody is not based on work load alone. The impact of HCV disease on patient well-being and health care costs cannot be overestimated.

Hepatitis C↗
PubMed1996

Erythropoietin and cytokine levels in the anemia of severe alcoholic liver disease.

PURPOSE: The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD. METHODS: sEPO, serum TNF-alpha, and serum gamma-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls). RESULTS: Mean hemoglobin (Hgb) was 11.2 +/- 0.3 g/dl for LD patients versus 11.4 +/- 0.4 g/dl for controls (p = 0.84). sEPO levels measured by ELISA were 29.6 +/- 4.1 units/liter in LD patients versus 25.4 +/- 5.4 units/liter in controls (p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly (p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN was not detected. CONCLUSIONS: These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.

Anemia↗
PubMed1996

Human hepatocyte growth factor in alcoholic liver disease: a comparison with change in alpha-fetoprotein. Department of Veterans Affairs Cooperative Study Group 275.

To evaluate the hepatic regenerative response in patients with alcoholic liver disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis were analyzed for hepatocyte growth factor (HGF) and alpha-fetoprotein (AFP). HGF concentration was elevated above healthy controls in 95% of the patients (median level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites, encephalopathy, AST bilirubin, and protime) all showed a more significant correlation with HGF concentrations than those of AFP. Patients with HGF levels below the mean (4 ng/ml) exhibited significantly better survival (median survival = 35 months vs. 8.5 months for those with HGF > or = 4 ng/ml; p = 0.007). Serum HGF levels were associated with various specific histologic features of alcoholic hepatitis that included, but were not exclusively related to, necrosis.

Energy Intake↗
PubMed1995

Protein consumption and hepatic encephalopathy in alcoholic hepatitis. VA Cooperative Study Group #275.

OBJECTIVE: Patients with alcoholic hepatitis frequently have moderate or severe malnutrition. Dietary protein intake may be restricted in these patients because of concurrent hepatic encephalopathy. To further evaluate the relationship between dietary protein intake and hepatic encephalopathy in alcoholic hepatitis, we evaluated prospectively gathered data from a study of 136 placebo-treated patients with moderate or severe alcoholic hepatitis conducted at eight Department of Veterans Affairs Medical Centers. METHODS: Physical examination, laboratory tests, and grade of hepatic encephalopathy were recorded at entry and every seventh day for the first 28 days of study. Average daily protein intake was calculated from dietary evaluation obtained by a registered dietitian at entry and again three times a week. RESULTS: Sixty-three percent of patients had hepatic encephalopathy at entry. Hepatic encephalopathy decreased over time. Time dependent regression analysis found low protein intake, along with high blood urea nitrogen (BUN) and high serum creatinine, to be independently associated with worsening hepatic encephalopathy. Similar analysis found low BUN and less malnutrition at entry into the study to be independently associated with improved hepatic encephalopathy. Higher protein intake was associated with improved hepatic encephalopathy in univariate (p = 0.01), but not multivariate, analysis. CONCLUSION: In patients with alcoholic hepatitis who can be treated with standard anti-encephalopathy medications (e.g., lactulose and neomycin), low protein intake is associated with worsening hepatic encephalopathy while a higher protein intake correlates with improvement in hepatic encephalopathy.

Blood Urea Nitrogen↗
PubMed1995

Alcohol modulation of immune function: clinical and experimental data. Veterans Affairs Cooperative Study Groups 119 and 275.

In both animal and human studies, ethanol seems to modulate host immune function. In a variety of animal studies, ethanol has been shown to decrease lymphocyte function and number. In human studies of patients with alcoholic hepatitis, these abnormalities were also seen with specific correlation with protein malnutrition. Hepatic pathological lesions were also correlated with lymphocyte subset infiltration. However, peripheral blood lymphocytes did not correlate consistently with hepatic histopathology.

Animals↗
PubMed1994

Phospholipid antibodies in alcoholic liver disease.

Alcoholic liver injury has been reported to be directed preferentially against the proteins of the cell membrane, sparing the phospholipids. However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases. We undertook this investigation to determine whether antiphospholipid antibodies were present in the serum of patients with alcoholic liver disease. We investigated seventy long-term alcoholic patients (> 80 gm ethanol/day for > 1 yr) and 8 normal nonalcoholic controls by means of enzyme-linked immunosorbent assay to determine whether serum antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid. Group 1 comprised alcoholic patients with normal liver function (n = 13), group 2 comprised alcoholic patients with abnormal liver function (n = 16), group 3 comprised patients with alcoholic hepatitis or cirrhosis (n = 41) and group 4 comprised nonalcoholic controls (n = 8). The antibody prevalence was 15% in group 1, 31% in group 2, 81% in group 3 and 0% in group 4. In group 3, 20 of 41 patients had antibodies against several cell membrane phospholipids (i.e., phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin and phosphatidylinositol). The antiphosphatidylethanolamine isotype was IgA or IgM in 25 of 41 of these patients. Both IgA (p < 0.01) and IgM (p < 0.008) antiphosphatidylethanolamine correlated significantly with disease severity. Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity.

Adult↗
PubMed1993

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.

Alcohol Drinking↗
PubMed1993

Relevance of anti-HCV reactivity in patients with alcoholic hepatitis. VA cooperative Study Group #275.

From 8 Department of Veterans Affairs Medical Centers, 296 patients with varying degrees of alcoholic liver disease were tested for hepatitis C (HCV) infection using an EIA and RIBA 2. A high frequency of positive response was observed with 13.9% reactive to both and an additional 4.4% positive only to RIBA 2 (total 18.3%). An evaluation of known risk factors (injection drug use and prior blood transfusions) failed to account for the mode of transmission in 42.6% of the HCV+ patients. The clinical severity of the liver disease and degree of liver pathology were nearly identical in HCV+ vs. HCV- patients. However, the process was accelerated in the HCV+ patients occurring at a 12.8% younger age (p < 0.0001) with a 43% increase in ALT (p = 0.05). The most striking differences were observed in immune parameters. In peripheral blood, total lymphocyte counts were increased 20% (p = 0.01) accompanied by a 56% increase in B cells (p = 0.01) and a 35% elevation of IgG levels (p = 0.0001) in HCV+ patients. T cell changes consisted of a 50% increase in CD8 cells (p = 0.047). However, lymphocyte infiltration into liver was not significantly different (HCV+ vs. HCV-) for any of the subsets studied (CD4, CD8, B cells, NK cells). The combined presence of HCV and alcohol injury did not significantly increase mortality but did significantly increase the number of hospitalizations from 2.4 to 4.0 per year (p = 0.0005).

Hepacivirus↗
PubMed1993

Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275.

BACKGROUND: The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury. METHODS: Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue. RESULTS: Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies. CONCLUSIONS: The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD.

CD3 Complex↗