Following are several published articles related to Hepatitis C that may be of interest to you.
BACKGROUND: No effective therapy exists for interferon non-responding chronic hepatitis C patients.
AIMS: Pilot study evaluating the potential efficacy and safety of triple antiviral therapy in interferon-alpha non-responders.
PATIENTS AND METHODS: Twenty consecutive adults with chronic hepatitis C who had failed to respond to a 6-month course of interferon alpha were randomly assigned to receive a combination of interferon alpha + oral ribavirin (double therapy), or the same combination + oral amantadine (triple therapy), for 6 months.
RESULTS: By the end of therapy, normal alanine transaminase (biochemical response) was obtained in 2 out of 10 patients on double therapy but in 7 out of 10 on triple therapy (p < 0.05), and negative serum hepatitis C virus (HCV) RNA (virological response) occurred in 1 out of 10 patients on double therapy but in 7 out of 10 patients on triple therapy (p < 0.01). Six months after therapy, biochemical response was sustained in 1 (double therapy) and 4 patients (triple therapy), respectively, and the virological response was sustained in no patient on double therapy but in 3 patients on triple therapy.
CONCLUSIONS: Triple antiviral therapy seems to be able to induce biochemical and virological responses in interferon alpha non-responders with chronic hepatitis C.
Very-low-fat Diet May Compromise Immunity but Increasing Fat in Diets May Maintain Immune System for Runners of 40 Miles per week
University at Buffalo
22-May-99
Trained runners who severely limit the amount of fat in their diets may be suppressing their immune system and increasing their susceptibility to infections and inflammation, a University at Buffalo study has shown. Trained runners who severely limit the amount of fat in their diets may be suppressing their immune system and increasing their susceptibility to infections and inflammation, a University at Buffalo study has shown.
In findings presented here today (May 22, 1999) at the fourth International Society for Exercise and Immunology Symposium, lead author Jaya T. Venkatraman, Ph.D., reported that running 40 miles per week on a diet composed of approximately 17 percent fat compromised the runners' immune response. The medium and high-fat diets, composed of approximately 32 and 41 percent fat respectively, left the immune system intact, and enhanced certain components, the findings showed. "The data suggest that higher-fat diets may lower the proinflammatory cytokines, free radicals and hormones, and may enhance the levels of anti-inflammatory cytokines," Venkatraman said. Venkatraman is an associate professor of nutrition in the Department of Physical Therapy, Exercise and Nutrition Sciences in the UB School of Health Related Professions.
Earlier studies published by a UB research group headed by David Pendergast, Ed.D., professor of physiology and biophysics, reported that competitive runners who increased the proportion of fat in their diets improved their endurance with no negative effect on weight, body composition, blood pressure, pulse rate or total cholesterol. (See editor's note) However, since a high level of fat was thought to be immunosuppressive, the researchers sought to determine if increasing dietary fat would compromise various elements of the immune system, while improving performance. "In general, moderate levels of exercise are known to enhance the immune system," said Venkatraman. "But high-intensity exercise and endurance exercise produce excess levels of free radicals, which may place stress on the immune system. "Since we have shown that athletes perform better on a higher-fat diet than on a low-fat diet, it was important to determine if the higher-fat diet would further compromise the immune system," she said. "We found that it did not, but the very-low-fat diet did." The study involved six female and eight male competitive runners who trained at 40 miles a week and were part of a larger performance study. They spent a month on their normal diets, followed by a month each on diets composed of approximately 17 percent, 32 percent and 41 percent fat. Protein remained stable at 15 percent and carbohydrates made up the difference. The immune status of the runners was obtained by analyzing concentrations of essential components of the immune system -- leukocytes, cytokines and plasma cortisol -- in blood samples taken before and after an endurance exercise test. The tests were conducted at the end of each four-week diet period.
Results showed that natural killer cells, a type of leukocyte and one of the body's defense mechanisms marshaled to fight infection, were more than doubled in runners after the high-fat diet, compared to the low-fat regimen. Levels of PGE2, inflammation-causing prostaglandins, increased after the endurance test and were higher when the runners were on the low-fat diet. This study is part of a larger investigation to determine the effects of dietary fat on performance, biochemical and nutritional status, and plasma lipids and lipoprotein profiles in distance runners being conducted by a study group composed of -- in addition to Venkatraman and Pendergast – Peter Horvath, Ph.D., associate professor in the UB Department of Physical Therapy, Exercise and Nutrition Sciences, and John Leddy, M.D., clinical professor of orthopedics and associate director of the UB Sports Medicine Institute.
BONE MARROW GIVES RISE TO FUNCTIONING LIVER CELLS
Bone marrow-derived cells give rise to fully functional liver cells, states a University of Pittsburgh study published May 14 in Science, yielding the first report that bone marrow-derived cells provide a lineage for cells of solid organs. 5/13/99
Bone marrow-derived cells give rise to fully functional liver cells, researchers at the University of Pittsburgh Medical Center have found through a series of transplant experiments, yielding the first report that such stem cells provide a lineage for cells making up solid organs. Study results, published in the May 14 issue of Science, suggest that bone marrow-derived cells could eventually repair or replace injured or diseased livers, reducing the need for transplantation. At a theoretical level, the findings disrupt the scientific dogma that plastic fetal cells are needed to generate the differentiated cells of adult organs.
"This is a critical paper that bridges a gap in our understanding of how the liver repairs itself under certain physiological conditions," said Bryon Petersen, Ph.D., research associate in pathology at the University of Pittsburgh's School of Medicine and lead investigator on the study. For more than 40 years, scientists have witnessed the appearance and proliferation of a distinctive group of cells, called oval cells, under special animal experimental conditions. Normally, healthy liver cells, or hepatocytes, regenerate an injured liver. But if hepatocyte division is suppressed experimentally and the liver is subsequently injured, oval cells appear on the scene. In this setting they proliferate, then transform into several types of functional liver cells, thus helping to repair the damaged organ. The origin of oval cells has remained controversial, although they are known to carry markers also seen on bone marrow cells. "Our animal experiments using cross-sex bone marrow transplants clearly show that bone marrow-derived cells eventually become fully functional liver cells, quite
probably through an intermediate oval cell," said Dr. Petersen. "The next step is finding the bone marrow stem cell giving rise to the oval cell or discovering the signal that the liver broadcasts to recruit such cells to the scene of injury."
Previous scientific reports have indicated that bone marrow cells give rise to two major tissue cell types -- mesenchymal cells that develop into bone and muscle and endothelial cells that form the lining of blood vessels. This report is the first to indicate that bone marrow cells give rise to the third tissue cell type, epithelial cells, which can develop into solid organs.
Ultimately, cultures of the malleable bone marrow stem cells could aid patients with fulminant hepatic failure, in which the liver is unable to repair itself, according to Dr. Petersen. Such cultures could also provide important reservoirs of cells that could be used for gene therapy to repair defective livers or to protect against viral infection. These cells could be transplanted back into the patient without risk of rejection.
As part of their research, the investigators took female rats and irradiated them to deplete their bone marrow. These females then received bone marrow from male rats of the same species. After nearly two months, the male/female mixtures, or chimeras, were treated with a chemical that prevents healthy liver cells from reproducing. One week later, the scientists chemically injured the liver. Fifteen days after the injury, the scientists removed the livers and probed them for a marker found only on the male Y chromosome. They located oval cells and hepatocytes that carried the marker. This discovery suggests that stem cells traveled from the bone marrow to the liver in response to injury and differentiated into oval cells, which in turn became functional hepatocytes.
Dr. Petersen and his colleagues repeated this experiment using another type of marker. In addition, they tested the hypothesis of bone marrow-derived hepatocytes by transplanting whole livers from one rat species without a specific tissue marker (L21-6-negative), into another rat species with the marker (L21-6-positive). After suffering an experimental injury, the transplanted L21-6-negative livers showed evidence of repair with L21-6-positive cells, suggesting they came from a source outside the liver.
Collaborators on the study include Bill Bowen; Ken Patrene; Wendy Mars, Ph.D.;
Art Sullivan, M.D.; Noriko Murase, M.D.; Sally Boggs, Ph.D.; Joel Greenberger, M.D.; and Judy Goff, Ph.D. All collaborators are with the University of Pittsburgh except Dr. Sullivan, who is with the department of hematology/oncology at McGill University in Quebec.
Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Patients with chronic HCV infection who had used intravenous drugs in the past had the greatest impairment in quality-of-life scores
Hepatology 1998 Jan;27(1):209-12
Foster GR, Goldin RD, Thomas HC Liver Unit, Imperial College School of Medicine at St
Mary's, St Mary's Hospital, London, England, UK.
The effects of chronic hepatitis C virus (HCV) infection, in the absence of cirrhosis, on patients' quality of life was assessed using the short form 36 (SF36) symptomatology questionnaire. Patients with chronic hepatitis C were polysymptomatic and had significant reductions in their SF36 scores for all of the modalities tested. Patients with chronic hepatitis B virus (HBV) infection showed a reduction in the SF36 scores that assessed mental functions, but they had no decrease in the scores that measured physical symptoms, indicating that the symptoms associated with chronic HCV infection are qualitatively different from those associated with chronic HBV infection. Patients with chronic HCV infection who had used intravenous drugs in the past had the greatest impairment in quality-of-life scores, but the reduction in quality-of-life scores was still found in patients who had never used drugs. The reduction in quality of life could not be attributed to the degree of liver inflammation or to the mode of acquisition of the infection. Hence, chronic infection with HCV per se gives rise to physical symptoms that reduce the quality of life of infected patients.
Pain or tenderness in in muscles or joints may be associated with HCV Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship.
Arch Intern Med 1997 Nov 24;157(21):2497-500
Buskila D, Shnaider A, Neumann L, Zilberman D, Hilzenrat N, Sikuler E
Department of Medicine B, Soroka Medical Center, Ben-Gurion University of the Negev, Beer
Sheva, Israel.
BACKGROUND: Fibromyalgia syndrome (FS) is a common disorder of diffuse pain in the muscles or joints accompanied by tenderness at specific tender points and a constellation of related symptoms. The potential role of infections in the pathogenesis of FS has only recently been investigated..
OBJECTIVES: To evaluate the prevalence of FS and to assess tenderness thresholds in patients infected with hepatitis C virus (HCV).
METHODS: The study included 90 patients with HCV, 128 healthy, anti-HCV-negative controls, and 32 patients with non-HCV-related cirrhosis. Tenderness was measured by manual palpation (18 tender points) and with a dolorimeter. Fibromyalgia syndrome was diagnosed according to the 1990 American College of Rheumatology criteria.
RESULTS: The diagnosis of FS was established in 14 patients (16%) with HCV, in 1 patient (3%) with non-HCV-related cirrhosis, and in none of the healthy controls (P < .001). Thirteen of the HCV-positive patients with FS were women. The patients with HCV had significantly (P < .01) more tender points (mean [+/- SD] 3.6 +/- 5.3) than the healthy controls (0.1 +/- 0.5) and the patients with non-HCV-related cirrhosis (1.2 +/- 2.7). Specifically, the patients with cirrhosis were most tender on both tenderness measures owing to the high proportion of women in this group. Patients with FS were significantly more tender than those without FS: their dolorimetry thresholds were 2.9 kg vs 6.0 kg (P < .001).
CONCLUSIONS: A high prevalence of FS was observed in patients infected with HCV, especially women. Recognizing FS in patients with HCV will prevent misinterpretation of FS symptoms as part of the liver disease and will enable the physician to reassure the patient about these symptoms and to alleviate them.
Small Study-- Hepatitis C virus infection and extrahepatic malignancies.
J Clin Gastroenterol 1997 Mar;24(2):87-9
Sikuler E, Shnaider A, Zilberman D, Hilzenrat N, Shemer-Avni Y, Neumann L, Buskila D
Department of Medicine B, Faculty of Health Sciences, Ben Gurion University of the Negev,
Beer-Sheva, Israel.
An association between chronic hepatitis C (HCV) infection and non-Hodgkin's lymphoma has been reported. We carried out this study to evaluate the possibility of an association between HCV infection and other extrahepatic malignancies. The medical records of 103 unselected, consecutively chosen, anti HCV-positive and 105 hepatitis B surface antigen (HBsAg)-positive patients attending liver clinic or hospitalized in the Department of Medicine were reviewed. Patients in whom anti-HCV positivity was detected after the malignancy was diagnosed were excluded. Malignancy rates in the general Israeli population were obtained from the Israeli cancer registry. The ages of anti-HCV-positive and HBsAg-positive patients were 54 +/- 16 (+/-SD) (range, 15-84) and 45 +/- 12 (range, 20-78) years, respectively; the male/female ratios were 50/53 and 73/32, respectively. Extrahepatic malignancies were found in 15 (14.6%) of the anti-HCV and in three (2.9%) of the HBsAg-positive patients. Thirteen of the malignancies were found among the 60 anti-HCV-positive patients aged > or =55 years old. Only one malignancy was found among the 28 HBsAg-positive patients of the same age group (p < 0.01). The rate of extrahepatic malignancies in these HCV-infected patients was significantly higher (p < 0.01) than expected in the general population. An association between HCV infection and extrahepatic malignancy may exist, but further prospective studies, including a large number of patients with HCV infection, will be necessary to define this observation.