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H J Alter

Publications and source records attributed to H J Alter.

At least 37 records · Page 2Linked to original sources

Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome.

Hepatitis C has emerged in recent years as the most common basis for liver disease in the United States, having infected an estimated 3.9 million people in this country and an estimated 170 million worldwide. Currently, it is the predominant reason for undergoing liver transplantation. The disease it causes is characterized by silent onset in most infected individuals, a high rate of viral persistence, and the potential for development of ever-worsening chronic liver disease, ranging from chronic hepatitis to cirrhosis and occasionally to hepatocellular carcinoma. Such progression, when it occurs, is also most commonly a silent process that may take 20-40, and occasionally even more, years to reach its end point. Because of these characteristics, it has been exceedingly difficult to accurately assess the natural history. Efforts to accomplish this have consisted of retrospective, prospective, and cohort studies. The most concerning data have derived from the retrospective study approach, generally performed at tertiary referral centers. Because these centers commonly attract persons with existing chronic liver disease, they have tended to describe a high rate of progression to cirrhosis and cancer. This "referral bias" is avoided in the prospective and cohort study approach, and data derived from these studies indicate a lower rate of progression and a correspondingly higher rate of either recovery or minimal liver disease. In this review, we briefly describe potential mechanisms of viral persistence; present detailed information on outcomes that have derived from retrospective, prospective, and cohort studies, involving both adults and children; examine the data regarding progression of fibrosis and of progression to hepatocellular carcinoma; consider cofactors that might enhance liver disease progression; and report the emerging data that suggest that spontaneous viral clearance may be higher than is currently believed. We conclude with the view that severe, life-threatening, progressive liver disease clearly occurs in a sizable minority (perhaps 30%) of chronically infected persons but speculate that fibrosis progression is neither linear or inevitable and hence that most hepatitis C virus carriers will have either a stable nonprogressive course or such indolent progression that they will die from an unrelated disease before the severe sequelae of hepatitis C become manifest or will have a sustained "curative" response to therapy. Although this view provides reasonable hope to the hepatitis C virus-infected individual, it does not deny the enormous burden this infection presents as the result of its high prevalence and global distribution. The sheer magnitude of the infected population will result in a large number with severe life-threatening liver disease even if the proportion of infected individuals that develop progressive disease is relatively small.

Acute Disease↗

Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis.

STUDY OBJECTIVE: Although several trials have been published evaluating intravenous magnesium sulfate as treatment for acute bronchospasm, its effectiveness for this indication remains unclear, prompting this meta-analysis. METHODS: All randomized controlled trials of adjuvant bolus intravenous magnesium sulfate for acute bronchospasm in the emergency department were eligible. Trials were identified using MEDLINE, EMBASE, bibliographies of selected articles, and review of abstracts of 4 scientific societies. Two reviewers abstracted data, one of whom was blinded to author and journal. Because studies used different spirometric outcome measures, effect size was calculated for each study by Hedges' method. The analysis used a fixed-effects model. One-way sensitivity analyses were performed to assess the influence of study quality and to search for publication bias. RESULTS: Abstracts from 210 articles were reviewed, yielding 40 trials, of which 9 were specific to bolus intravenous magnesium sulfate in the ED, in doses from 1.2 to 2 g, or an equivalent pediatric dose. Combined results across 9 studies including 859 patients showed a posttreatment effect size of 0.162 for patients treated with intravenous magnesium sulfate (95% confidence interval 0.028, 0.297; P =.02). In sensitivity analyses exploring the effects of study quality and publication bias, the summary effect ranged from 0.127 to 0.206. No serious adverse events were reported. CONCLUSION: Adjuvant bolus intravenous magnesium sulfate in acute bronchospasm appears statistically beneficial in improving spirometric airway function by 16% of a SD. Although the clinical significance of this is uncertain, given the safety of intravenous magnesium sulfate therapy and its relatively low cost, it should be considered, absent contraindications, in patients with moderate to severe acute bronchospasm.

Acute Disease↗

Prevalence of hepatitis G virus in patients with hemophilia and their steady female sexual partners.

BACKGROUND: Hepatitis G virus (HGV), also known as GB virus C, is a newly discovered Flavivirus that is transmissible by blood transfusion and other possible routes. OBJECTIVE: To study the risk of sexual transmission of HGV in female sexual partners of men with hemophilia (n = 161 couples). METHODS: Blood samples obtained from 11 medical centers were analyzed for (1) HGV RNA by polymerase chain reaction; (2) antibodies to HGV by enzyme immunoassay; and (3) other viruses and T-cell counts by routine laboratory tests. Subjects completed a questionnaire that assessed sexual intercourse frequency, number of sexual partners, condom usage, sexually transmitted diseases, illicit drug usage, and needlestick or broken-glass injuries. RESULTS: The HGV infection (RNA +/- antibody positive) prevalence was 48% among men and 21% among women. Prevalence of hepatitis C virus, hepatitis B virus, and HIV among men was 99%, 94%, and 86%, compared with 3%, 11%, and 12% among women, respectively. The odds ratio for HGV infection for women with an HGV-positive male sexual partner was 2.14 (P = 0.06) without adjustment, and 2.77 (P = 0.03) with adjustment for other variables, none of which were independently significant. CONCLUSION: These results suggest a low level of HGV sexual transmission.

Antibodies, Viral↗

Seroprevalence of hepatitis C virus in the general population of northwest Tanzania.

Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.

Adolescent↗

The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology.

Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.

Adolescent↗

Characterization of the humoral and cellular immune responses against hepatitis C virus core induced by DNA-based immunization.

Hepatitis C Virus (HCV) causes most cases of posttransfusion hepatitis. Chronic HCV infection is highly related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Current therapies are only minimally effective and no vaccine has been developed. DNA-based immunization could be of prophylactic and therapeutic value for HCV infection. By intramuscular inoculation in BALB/c mice with an HCV recombinant plasmid pCI-HCV-C, we found significant levels of IgM antibody, but no significant IgG rise. After boost the immunized mice with recombinant HCV-core protein (cp1-10; 1-164aa), the anticore IgG, verified by Western-blotting, rose rapidly, which was two weeks earlier than that with control plasmid. Spleen cells from pCI-HCV-C immunized mice gave higher proliferation index (PI) than control (P < 0.05). The PI of cp1-10 boosted mice was even higher. Proliferation blocking assay with mAb proved the responding cell to be of CD4+ CD8- phenotype, supporting specific priming of T helper cells. A 51Cr-releasing CTL assay specific for HCV-core was developed, and a specific CTL response against HCV-core was demonstrated in both pCI-HCV-C immunized mice and mice boosted with cp1-10. Strong cytotoxic activity against peptide-pulsed p815 cells (H-2d), but not EL-4 cells (H-2b), suggested MHC class I restriction of the CTL activity. Blocking of CTL with mAb proved the effector cells to be of CD4- CD8+. Three CTL epitopes in HCV-core protein were demonstrated. We failed to detect CTL when immunized only with core protein. The results suggested that vaccination with HCV-core derived DNA sequences could be an effective method to induce humoral and cellular immune responses to HCV.

Animals↗

Expression and characterization of HIV type 1 envelope protein associated with a broadly reactive neutralizing antibody response.

We have studied envelope protein from a donor with nonprogressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus NA. DNA was extracted from lymphocytes, which had been collected approximately 6 and 12 months prior to the time of collection of the cross-reactive serum, and env genes were synthesized, cloned, expressed on pseudoviruses, and phenotyped in NA assays. Two clones from each time point had identical V3 region nucleotide sequences, utilized CCR5 but not CXCR4 for cell entry, and had similar reactivities with reference sera. Analysis of the full nucleotide sequence of one clone (R2) demonstrated it to be subtype B and have normal predicted glycosylation. R2 pseudovirus was compared with others expressing env genes of various clades for neutralization by sera from U.S. donors (presumed or known subtype B infections), and from individuals infected with subtypes A, C, D, E, and F viruses. Neutralization by the U.S. sera of R2 and other clade B pseudoviruses was low to moderate, although R2 was uniquely neutralized by all. R2 was neutralized by 3/3, 3/3, 2/5, 5/8, and 3/4 clade A, C, D, E, and F sera, respectively. R2 and a clade E pseudovirus were neutralized by largely complementary groups of sera, potentially defining two antigenic subgroups of HIV-1. The results suggest that the epitope(s) that induced the cross-clade reactive NA in donor 2 may be expressed on the R2 envelope.

Amino Acid Sequence↗

Transfusion-associated TT virus infection and its relationship to liver disease.

TT virus (TTV) has been proposed as the causative agent of non-A to E hepatitis. We studied the association between TTV viremia and biochemical evidence of hepatitis in blood donors and prospectively-followed patients. TTV was found in 7.5% of 402 donors and in 11.0% of 347 patients before transfusion. The rate of new TTV infections was 4.7% in 127 nontransfused, and 26.4% in 182 transfused patients (P <.0001). The risk of infection increased with the number of units transfused (P <.0001). The rate of new TTV infections in 13 patients with non-A to E hepatitis (23.2%) was almost identical to the rate in 124 patients who were transfused, but did not develop hepatitis (21.8%). Of 45 patients with acute hepatitis C, 40.0% were simultaneously infected with TTV. TTV did not worsen the biochemical severity (mean ALT: 537 in TTV+; 550 in TTV-) or persistence of hepatitis C. In non-A to E cases, the mean ALT was 182 in those TTV-positive and 302 in TTV-negatives. No consistent relationship between alanine transaminase level and TTV DNA level was observed in 4 patients with long-term, sequential samples. Of 21 viremic subjects, 67% cleared TTV within 5 years (38% in 1 year); 33% were viremic throughout follow-up extending to 22 years. We conclude that TTV is a very common, often persistent infection that is transmitted by transfusion and by undefined nosocomial routes. We found no association between TTV and non-A to E hepatitis and no effect of TTV on the severity or duration of coexistent hepatitis C. TTV may not be a primary hepatitis virus.

Blood Donors↗

Redefining the HIV-infectious window period in the chimpanzee model: evidence to suggest that viral nucleic acid testing can prevent blood-borne transmission.

BACKGROUND: Although it is rare, blood-transmitted HIV infection can occur when a donor presents in the window period between HIV-1 exposure and the first appearance of detectable p24 antigen. STUDY DESIGN AND METHODS: To study this seronegative window period, a chimpanzee (X034) was inoculated with 38 median tissue culture infective doses of HIV-1 IIIB; serum and peripheral blood mononuclear cells were obtained one to two times per week for 12 weeks and then biweekly for 12 weeks. Infectivity was monitored by the detection of serum HIV RNA, cell-associated HIV DNA, p24 antigen, and anti-HIV and by co-culture methods. RESULTS: No HIV markers were noted until 5 weeks after inoculation, at which time virus was isolated and HIV RNA and DNA were detected in plasma and cells, respectively. Anti-HIV and HIV p24 antigen were not present until 8 weeks after inoculation. Plasma and cells obtained from Chimpanzee X034 3 or 4 weeks after exposure were then sequentially inoculated into a second chimpanzee (X176); no HIV infection was observed in this animal during serial follow-up for 24 weeks after each inoculation. In contrast, when the fifth-week HIV-1 RNA- and DNA-positive sample was inoculated, Chimpanzee X176 was unequivocally infected with HIV-1. CONCLUSIONS: Nucleic acid testing narrowed the seronegative window by 3 weeks (37%). More important, there was no demonstrable infectivity in either plasma or peripheral blood mononuclear cells obtained before molecular markers were detectable. This suggests that the infectious window may be considerably shorter than the total window as measured from exposure and that nucleic acid testing might not only shorten the seronegative window, but totally prevent transfusion-transmitted HIV infection.

Animals↗

Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus.

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.

Adult↗

Health status disparities among public and private emergency department patients.

OBJECTIVE: To explore whether patients in a public ED had poorer health than patients in a private ED, the authors compared the physical and mental health statuses of patients seeking emergency care. METHODS: A cross-sectional observational study of all adult patients, regardless of acuity, seen during two 24-hour periods in spring 1997 in an urban county trauma center (68,000 annual visits) and a private community ED (35,000 annual visits). Scores on the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scales of the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) were compared between sites, with published national norms, and with hospital admission. RESULTS: Of 571 eligible patients, 392 (69%) completed the SF-12. Patients in the public ED had a mean PCS score of 40.1, compared with 43.7 for patients in the private ED, for a difference of 3.6 points (p < 0.01; 95% CI = 0.9 to 6.1). After controlling for age, sex, ethnicity, triage acuity, ambulance arrival, and insurance status, this difference increased to 3.9 points (p = 0.02; 95% CI = 0.7 to 7.0). The mean MCS score among public ED patients was 44.1, compared with 46.5 in the private ED population, for a difference of 2.4 (p = 0.08; 95% CI = -0.3 to 5.0); after adjustment this difference increased to 2.5 (p = 0.15; 95% CI = -0.9 to 5.8), but remained statistically not significant. While all scores were significantly lower than national norms (mean PCS 50.1, mean MCS 50.0), patients in the public ED scored consistently lowest. PCS score was significantly inversely correlated with admission, with each point decrease in PCS score increasing the odds of admission by 0.05 (95% CI = 0.01 to 0.08), and conferring an odds ratio of 5.1 (95% CI = 1.2 to 21.1) for admission among the 25th percentile for PCS scores. CONCLUSIONS: Patients seeking care in the public ED had lower adjusted physical health status scores than comparable patients obtaining care in a private ED. The SF-12 is sufficiently responsive to detect hypothesized differences between ED populations, and correlates well with admission decisions.

Adult↗

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection.

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

Adult↗

Past and present hepatitis G virus infections in areas where hepatitis C is highly endemic and those where it is not endemic.

We reported previously on an area in Japan where over 30% of the inhabitants were positive for hepatitis C virus (HCV) antibody. In the present study, clinical features of hepatitis G virus (HGV) infection in this area of high endemicity were compared to those in an area where HCV is not endemic. A total of 400 individuals were selected randomly from those who were medically screened for liver disease in 1993; 200 were from the high-endemicity area, and the other 200 were from the no-endemicity area. HGV RNA was measured by reverse transcription and PCR with primers in the 5' noncoding region. Antibody to HGV envelope protein E2 was measured by an enzyme-linked immunosorbent assay. Prevalence of any HGV marker in the high-endemicity area (32%) was significantly (P < 0.0001) higher than that in the no-endemicity area (6%); similar differences, 32% versus 3% (P < 0.0001), had been observed for HCV markers (HCV RNA and HCV antibody). In areas of both high and no endemicity, HCV markers were significantly more prevalent in individuals with any HGV marker than in those without HGV markers, and age-specific prevalence of HGV markers was distributed similarly to that of any HCV marker. Among possible routes of HGV transmission that were analyzed, folk medicine was significant in the high-endemicity area, but blood transfusion was the major route in the no-endemicity area. The rate of accompanying viremia in HGV infection (15%) was significantly lower than that in HCV infection (78%) (P < 0.0001). In conclusion, HGV infection was highly prevalent in the area of high HCV endemicity and was closely associated with HCV infection. HGV seemed to be transmitted via the practice of folk medicine as well as blood transfusion. HGV resulted in a chronic carrier state less frequently than did HCV.

Adolescent↗

The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease.

BACKGROUND: The role of hepatitis G virus (HGV) in transfusion-associated infection and its relation to liver disease are not well understood. METHODS: Serum samples collected between 1972 and 1995 from 357 transfusion recipients, 157 controls who did not receive transfusions, 500 randomly selected volunteer blood donors, and 230 donors of blood received by HGV-infected patients were tested for HGV RNA by qualitative and quantitative polymerase-chain-reaction assays. Samples obtained before transfusion and serially after transfusion from 79 of the 81 transfusion recipients who had transfusion-associated non-A, non-B hepatitis were available for testing. RESULTS: Of the 79 patients with transfusion-associated hepatitis, 63 (80 percent) had infections related to the hepatitis C virus (HCV) and 3 had preexisting HCV and the cause of their acute hepatitis could not be determined; of the remaining 13 patients, 3 had acute HGV infection, and 10 were infected with unidentified agents. Six of the 63 patients with HCV infection who were tested (10 percent) were also infected with HGV. The three patients infected only with HGV had mild hepatitis (mean peak alanine aminotransferase level, 198 U per liter; none had jaundice); the levels of alanine aminotransferase and HGV RNA were not well correlated. The combined HCV and HGV infections were no more severe than HCV infections alone; the alanine aminotransferase values paralleled the levels of HCV RNA, but not those of HGV RNA. There were 35 HGV infections among the 357 transfusion recipients; only 3 had hepatitis with HGV as the sole viral marker. One of the 157 controls and 7 of the 500 randomly selected blood donors (1.4 percent) had detectable HGV RNA. In all eight instances in which a transfusion recipient had acute HGV infection after transfusion and samples from all donors could be tested, at least one HGV-positive donor was identified. CONCLUSIONS: HGV was common in a group of volunteer blood donors, and it can be transmitted by transfusion. Most HGV infections were not associated with hepatitis. HGV did not worsen the course of concurrent HCV infection. No causal relation between HGV and hepatitis has been established.

Acute Disease↗

Humoral immune response to the E2 protein of hepatitis G virus is associated with long-term recovery from infection and reveals a high frequency of hepatitis G virus exposure among healthy blood donors.

The second envelope protein (E2) of the hepatitis G virus (HGV) was expressed in Chinese hamster ovary (CHO) cells and showed a molecular weight of approximately 60 to 70 kd, with 15 to 25 kd of the size contributed by N-linked glycosylation. An enzyme-linked immunosorbent assay (ELISA) using HGV-E2 was developed to test for antibodies to this protein (anti-E2) in human sera. High sensitivity was achieved by developing monoclonal antibodies (mAbs) to HGV-E2, which were used as capture antibodies in the ELISA. Our studies revealed that 16% of healthy Spanish blood donors were exposed to HGV, indicating that additional routes of viral transmission besides parenteral exposure might exist. An even higher prevalence of exposure to HGV (52%-73%) was found in several groups at risk of parenteral exposure to infectious agents, i.e., intravenous drug users, transfusion history, hemophiliacs, and hepatitis C virus (HCV)-positive patients. Most anti-E2-positive patients were HGV-RNA-negative and vice versa, indicating an inverse correlation of these two viral markers. A panel of 16 posttransfusion patients followed for up to 16 years revealed that patients who develop an anti-E2 response become HGV-RNA-negative, while patients who do not develop anti-E2 are persistently infected. Immunity to HGV seems to be long-lasting, because circulating antibody to E2 could still be detected 14 years after seroconversion. Sequence comparisons showed that E2 is highly conserved among isolates collected worldwide, indicating that immune escape variants are not common in HGV infections. This reflects on a molecular level why HGV infections usually are cleared spontaneously by the host. However, possible mechanisms of HGV persistence, as found in some patients, remain to be elucidated.

Amino Acid Sequence↗

Hepatitis C in asymptomatic blood donors.

Among 248 asymptomatic blood donors positive for antibody to hepatitis C virus (anti-HCV) enrolled in a long-term prospective study, 86% had chronic HCV infection and 14% appeared to have recovered as assessed by serial determinations of serum alanine aminotransferase (ALT) levels and HCV RNA by polymerase chain reaction. Established parenteral risk factors for HCV transmission were identified in 75% of donors. In addition, there was a strong independent association between HCV positivity and cocaine snorting, suggesting that shared snorting devices may be a covert route of parenteral transmission. Ear piercing in males was also significantly associated with transmission. There was no evidence for sexual spread. Although the majority of HCV carriers had both biochemical and histological evidence of chronic viral hepatitis, the extent of liver injury was generally mild. Among a larger population of 280 HCV RNA-positive donors, 17% had repeatedly normal ALT levels, 45% had levels that did not exceed twice, and only 22% had levels that exceeded five times the upper limit of the normal range. Among 81 patients who underwent liver biopsy, only 13% had evidence of severe hepatitis (8%) or cirrhosis (5%), despite a duration of infection that generally exceeded 15 years. No severe histological lesions were observed in blood donors with chronic HCV infection who had repeatedly normal ALT levels. In both donors and blood recipients, the frequency of severe morbidity or mortality related to HCV infection was less than 10% during the first two decades of infection. Further long-term studies are required to see if the progression to severe outcomes continues to accrue at this slow pace or whether it accelerates during subsequent decades.

Blood Donors↗