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Biomedical subjects

L B Seeff

Publications and source records attributed to L B Seeff.

At least 37 records · Page 2Linked to original sources
PubMed2000

Strategies for assessing the long-term consequences of Hepatitis C virus infection.

The entity of non-A, non-B (NANB) hepatitis was identified in the early 1970's in the course of studies of transfusion-associated hepatitis. It was first thought to be a mild illness because most persons identified with acute hepatitis lacked symptoms, had mild enzyme elevations, and were not jaundiced. It was only after realisation that enzyme elevations persisted in almost all affected persons, and that about 20% of those undergoing liver biopsy showed fibrosis and even cirrhosis, that concern began to grow. This escalated further when it became clear that another potential outcome was evolution to hepatocellular carcinoma, a process that could take 20 to 40 years to develop. The discovery of the hepatitis C virus (HCV) in 1989 proved revolutionary, indicating that most (80% or more) of the NANB hepatitis cases were caused by this virus, and reinforcing the evidence that the majority of those acutely infected developed persistent chronic disease that could culminate in cirrhosis and even cancer. The first efforts to assess the natural history were retrospective studies that confirmed the long duration of infection, but identified a high rate of liver disease progression. Because they were conducted in tertiary care centers, the majority of patients that they studied already had potentially severe disease when first seen. Subsequent prospective studies described a more benign outcome, but most were of relatively short duration and therefore could not provide the needed long-term outcome information. Recently, a series of retrospective-prospective (non-concurrent prospective) studies involving transfusion recipients, children, women, and persons with community-acquired HCV infection suggest that evolution to cirrhosis is highly variable (2 to 20% at 20 years) and that progressive disease may be limited and not universal. Recent data suggest also that spontaneous recovery from infection may be higher than previously believed.

Journal Article↗
PubMed1999

Natural history of hepatitis C.

It is now widely accepted that 85% or more of individuals with acute hepatitis C virus (HCV) infection progress to chronic hepatitis, and chronic hepatitis C is a known risk factor for cirrhosis and hepatocellular carcinoma (HCC). However, there has been much controversy about the inevitability of developing cirrhosis and HCC and the time frames in which they are likely to occur. Natural history studies have provided varying estimates of the risk of progression in chronic hepatitis C. Part of this variation may be a result of viral-specific, host, and/or environmental factors, but much of it undoubtedly is a result of the difficulties of doing natural history studies in this disease: acute onset is rarely identified, chronic infection is often asymptomatic, and the duration of disease is prolonged. Three types of studies--prospective, retrospective, and retrospective-prospective (nonconcurrent prospective)--have attempted to determine the clinical outcomes of chronic HCV infection and have provided widely varying estimates. The combined population data indicate that the disease progresses slowly over approximately 30 years, on average. Approximately 20% of infected individuals will progress to fibrosis and cirrhosis. Of these, approximately 20% will progress to HCC. The likelihood of progression appears to be independent of genotype or viral load but increases with alcohol intake, male sex, age over 40 years at infection, and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). Results of ongoing nonconcurrent studies are needed to determine disease progression in the third, fourth, and fifth decades of infection and to better define the factors that affect progression.

Adult↗
PubMed1997

Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial.

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.

Administration, Oral↗
PubMed1997

Natural history of hepatitis C.

Approximately 85% of persons with acute hepatitis C develop chronic hepatitis as determined by persistently abnormal serum enzymes and/or viremia (hepatitis C virus [HCV] RNA). Both the acute and chronic illnesses are predominantly asymptomatic. For this reason and because the chronic illness runs an extremely protracted course, it has been difficult to accurately define the frequency and rate of progression to symptomatic or end-stage liver disease, specifically cirrhosis and hepatocellular carcinoma (HCC). Three evaluation strategies have been used. The first, prospective studies beginning from disease onset, have identified over 8 to 14 year follow-up periods that morbidity (symptoms, cirrhosis) and mortality (hepatic failure, HCC) are modest in frequency. The second, prospective studies of subjects with already established chronic liver disease, have demonstrated high rates of development of cirrhosis, HCC, and mortality over relatively short follow-up periods. The third, retrospective/prospective (nonconcurrent prospective) studies, has consisted of follow-up of recipients of HCV-contaminated immunoglobulin and of transfusion recipients from five enzyme-monitored transfusion studies of the early 1970s. The former study identified no mortality, trivial morbidity, and minimal cirrhosis 17 years after infection. The latter, involving hepatitis cases and matched nonhepatitis controls studied over a 20-year period, demonstrated no increase in all-cause but a slight increase in liver-related mortality. Clinically evident chronic liver disease was noted to be minimal among those in follow-up with biochemically defined chronic hepatitis whose biopsy specimens showed no cirrhosis, but common among those with histologically detected cirrhosis. More than 90% of subjects with an original diagnosis of transfusion-related hepatitis C have remained positive for antibody to HCV (anti-HCV), most with persistent viremia. Two thirds of the anti-HCV-positive individuals have biochemically defined chronic hepatitis, whereas one third have persistently normal enzymes. Taken together, available data suggest that in the first two decades after infection, mortality and morbidity are modest in frequency. Both can be expected to increase as the disease advances to the third and fourth decades after acute infection, especially among those with established cirrhosis. The outcome among those with chronic hepatitis but without cirrhosis remains to be determined.

Chronic Disease↗
PubMed1997

The natural history of chronic hepatitis C virus infection.

In conclusion, the natural history of chronic HCV infection has not yet been fully defined. Current data suggest that the process runs an indolent course during the first two decades after initial infection, accounting for modest morbidity and mortality. Serious sequelae are more likely to emerge as the disease process enters the third and fourth decades after infection. These sequelae will presumably be concentrated among those whose liver biopsies display features of cirrhosis, but seem less likely to effect those with liver biopsy evidence of chronic hepatitis alone unless their disease advances to cirrhosis. The frequency of progression from chronic hepatitis to cirrhosis as the disease process enters the third decade remains to be determined. Associated chronic alcoholism appears to be an important additive factor, but other factors that might promote disease progression need to be defined. It seems probable that end-stage liver disease will result in only a proportion of infected individuals. If so, the challenge is to learn how to determine for each individual during the course of their chronic illness what outcome can be expected.

Disease Progression↗
PubMed1997

Prevalence of hepatitis C virus associated cryoglobulinemia at a veterans hospital.

OBJECTIVE: To prospectively evaluate the prevalence and clinical spectrum of cryoglobulinemia in a population infected with the hepatitis C virus (HCV). METHODS: Inpatients and outpatients at the Veterans Affairs (VA) Medical Center were recruited for study. Sixty-nine patients with HCV and 68 anti-HCV negative, age and sex matched controls were evaluated for the prevalence of cryoglobulinemia. Clinical and laboratory profiles were obtained in all patients and rheumatologic complaints were sought in 58 anti-HCV positive patients. RESULTS: Twenty-nine (42%) of 69 anti-HCV positive patients and no controls had cryoglobulinemia (p < 0.001). A history of intravenous drug abuse and excessive alcohol ingestion was more prevalent in the anti-HCV positive group compared to controls, (p < 0.001 and p = 0.02, respectively), but was unrelated to the presence or absence of cryoglobulinemia. Of 58 anti-HCV positive patients evaluated for rheumatologic complaints, 12 (21%) reported symptoms; 9 (41%) of 22 with cryoglobulinemia and 3 (8%) of 36 without cryoglobulinemia (p < 0.01). No patient had vasculitis. Antinuclear antibody (ANA) and rheumatoid factor (RF) were evaluated in 19 anti-HCV positive patients with cryoglobulinemia. About one-half were positive for ANA or RF, fewer than 50% of whom had rheumatologic symptoms. Nineteen of the 29 patients with cryoglobulinemia were available for followup after one year. Ten of 19 revealed only trace (< 5%) cryoglobulinemia; 7 were type III, one type I, and none were type II. The character of the remaining 2 cryoglobulins was unknown. Twenty-five liver biopsy specimens were available for review; there were no histological differences between patients with and without cryoglobulinemia. CONCLUSION: The prevalence of HCV related cryoglobulinemia at a VA hospital was 42% and was most often of the type III variety. Although mild rheumatologic symptoms were common in HCV infected patients with cryoglobulinemia, no specific syndrome denoted its presence. The absence of any specific rheumatologic disease in this cohort implies that the pathogenesis of diseases such as essential mixed cryoglobulinemia is multifactorial and that low levels of type III cryoglobulinemia in HCV infected patients are not specific for the diagnosis.

Biopsy↗
PubMed1996

The natural history of chronic hepatitis C infection.

Hepatitis C is among the most common causes of chronic liver disease affecting approximately 1% of the world's population. End-stage hepatitis C virus (HCV)-related chronic liver disease is the leading indication for orthotopic liver transplantation worldwide. Despite these facts, many questions regarding the natural history of HCV infection remain unanswered. Is progression to end-stage liver disease inevitable? Over what time period does it occur? If progression is not inevitable, can we identify those persons destined to have end-stage liver disease and possibly prevent or slow progression?

Disease Progression↗
PubMed1996

New hepatitis A vaccines and their role in prevention.

The hepatitis A virus (HAV) accounts for 20 to 25% of clinically apparent hepatitis cases worldwide. It generally causes mild to moderately severe acute illness. The serological prevalence of this virus is high in underdeveloped countries where poor sanitary conditions facilitate the spread of the virus. The Sentinel Counties studies of the Centers for Disease Control in the US have identified a number of factors associated with the acquisition of HAV, including household members, homosexual men, children and caretakers in day-care facilities who come into contact with individuals who are incubating or in the early phases of HAV infection. Poor sanitary conditions, international travel and intravenous drug use promote the transmission of the virus. However, in 40% of cases, no risk factor can be identified. Immune globulin (IG), once used exclusively for the prevention of HAV infection, acts by provoking passive-active immunity. It prevents clinical disease but permits subclinical disease to develop. Unfortunately, IG provides protection for only 3 to 6 months, necessitating repeat inoculation for exposure extending over 180 days. More recently, a number of live-attenuated and formalin-inactivated HAV vaccines have been developed and studied. The vaccines are well tolerated and highly immunogenic, with only mild local adverse reactions. The suggested dose and schedule is 720 ELISA units of inactivated vaccine injected intramuscularly at 0, 1 and 6 months. A single intramuscular dose of 1440 ELISA units followed 6 to 12 months later by a further injection has also been approved by the FDA and is available in several European countries. 90% of vaccines achieve protective levels of anti-HAV after the first injection. Routine use of the HAV vaccine for pre-exposure prophylaxis is expected to replace IG in healthy adults travelling to endemic areas, children in day-care centres, military personnel, homosexual men, healthcare workers and residents in institutions for the mentally disabled.

Cost-Benefit Analysis↗
PubMed1995

Hepatotoxicity of analgesics and anti-inflammatory agents.

Nearly all analgesic and anti-inflammatory agents have the potential for hepatic injury. Most nonsteroidal anti-inflammatory drugs (NSAIDs) produce injury in an unpredictable fashion by way of an idiosyncratic (immunologic versus metabolic) mechanism, whereas acetaminophen and aspirin are more predictable because they produce injury in a dose-dependent manner by way of intrinsic toxicity. Both acetaminophen and aspirin may produce hepatotoxicity despite therapeutic intent. This article discusses specific NSAIDs available in the United States and abroad and their associated hepatotoxicity and carefully considers acetaminophen-related hepatotoxicity reviewing risk factors for injury, clinical features, prognosis, and management.

Analgesics↗
PubMed1993

Mortality follow-up of the 1942 epidemic of hepatitis B in the U.S. Army.

The hypothesis that adult infection with the hepatitis B virus in the United States leads to a carrier state with a high risk of primary liver cancer was tested in two ways: (a) a cohort mortality study of U.S. Army veterans given yellow fever vaccine contaminated with hepatitis B virus in 1942 and controls and (b) a case-control study comparing veterans with hepatocellular carcinoma in Veterans Affairs hospitals with matched controls with respect to receipt of contaminated vaccine in 1942. Three groups totaling 69,988 men were the subjects of the cohort study: group 1 comprised men hospitalized with hepatitis in 1942, group 2 comprised men subclinically infected in 1942 and group 3 comprised controls who entered service after the contaminated vaccine was discontinued. Hepatocellular carcinoma cases (n = 24) and control subjects (n = 63) derived from Veterans Affairs hospital discharge files were the subjects of the case-control study. Group comparisons of death rates from liver cancer were refined by expert review of records to select hepatocellular carcinoma from among all causes of death so diagnosed in the cohort study. Slightly excess mortality was found for hepatocellular carcinoma in group 2 (subclinical hepatitis B) but not for group 1 (overt hepatitis B) compared with group 3 (controls) (p = 0.08). Mortality from nonalcoholic chronic liver disease was less in group 2 than in group 3. In the case-control study, the relative risk for hepatocellular carcinoma conferred by receipt of contaminated vaccine was estimated as 3.3 (p = 0.06). We conclude from the cohort study that immunocompetent adult males rarely become carriers after hepatitis B virus infection, probably far less often than the frequently assumed rate of 5% to 10%. The small excess liver cancer mortality seen in the cohort study and the results of the case-control study are consistent, nevertheless, with the now well-established etiological role of hepatitis B virus infection in liver cancer.

Adult↗
PubMed1992

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease.

Alcoholism↗