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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

New England Journal of Medicine, Volume 388, Issue 1, Page 55-69, January 2023.

Journal of Medical Virology, Accepted Article.

IntroductionAn estimated 290 million people are living with hepatitis B virus (HBV) worldwide; in Spain, the prevalence of hepatitis B virus surface antigen (HBsAg) is 0.4%. In our setting, many HBsAg-positive individuals are not linked to care, which implies a barrier to receiving treatment and controlling the infection. The main objective of this project is to evaluate the performance of a programme designed to achieve appropriate linkage to specialist care of HBsAg-positive individuals, newly tested or previously tested and lost to follow-up.Methods and analysisThis is a retrospective and prospective study in which all HBsAg-positive cases recorded in the microbiology database will be identified. The retrospective phase will include cases detected between 2018 and 2020, and the prospective phase will run from January 2021 to June 2022. The project will be carried out in a tertiary university hospital covering the northern health area of Barcelona with a catchment population of 450 000 inhabitants and 16 affiliated primary care centres. The central laboratory detects approximately 1200 HBsAg-positive individuals every year; therefore, we expect to identify around 4000 patients over the duration of the project. The medical records of HBsAg-positive individuals will be consulted to identify and retrieve those who have not been appropriately linked to care. Candidates will be contacted to offer specialist disease assessment and follow-up. A website will be created to provide HBV-related information to primary care physicians, and a mobile phone application will be available to patients to improve the linkage circuits and ensure follow-up continuity.Ethics and disseminationThe Vall d’Hebrón Hospital Ethics Committee (PR(AG)201/2021) and the Spanish Agency of Medicines and Medical Devices approved this study. The findings will be disseminated through peer-reviewed publications and conference presentations. This programme could increase the number of HBsAg-positive individuals properly linked to care and achieve better HBV monitoring, which will have a positive impact on WHO’s viral hepatitis elimination goals.…

ABSTRACTBackgroundChronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in NAs successfully treated patients.MethodsA series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from NAs successfully treated patients. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated.ResultsThree out of six successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated from approximately 7.42 weeks to infinite. Moreover, hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA (rcDNA) in four out of seven liver needle biopsies.ConclusionsWe therefore conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas the greatest amount of cccDNA reservoir persists over time.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Due to acceptable safety and tolerability, RO7020531 should continue to be developed for the treatment of patients with chronic HBV infection.

Abstract Background Although the prevalence of hepatitis B in Guangzhou, China, is high, the epidemiological trends are not well-documented. We aimed to analyse newly reported hepatitis B cases in Guangzhou between 2009 and 2020 to explore the epidemiological trends and provide insights for the development of control measures. Methods Information on the population and new cases of hepatitis B in Guangzhou between 2009 and 2020 was obtained from the China Information System for Disease Control and Prevention, which was used to calculate the annual notification rates of hepatitis B by sex, age group (0–9; 10–19; 20–29; 30–39; 40–49; 50–59; ≥ 60 years), and location (urban or rural). Joinpoint regression analysis was used to analyse the temporal trends and calculate the average annual percentage change (AAPC) and annual percentage change (APC) for each identified trend line segment. Results Between 2009 and 2020, 287,034 new cases of hepatitis B were cumulatively reported. The average annual notification rate was 181.13/100,000, and the notification rate showed a long-term downward trend during the period 2009–2020, with an annual decrease of 6.30% (APC − 6.30%; 95% CI − 7.56 to − 5.02%). Men had a significantly higher notification rate than women; however, the sex ratio decreased from a maximum of 2.34 in 2010 to a minimum of 1.54 in 2020. A downward trend in the notification rate was observed in urban areas and an upward trend was observed in rural areas, with an increase in the rural/urban ratio from 0.46 in 2012 to 1.57 in 2020. The notification rate for all age groups showed a decreasing trend from 2009, with the exception of the 50–59 years and ≥ 60 years groups, whose notification rates began to decrease from 2014 and 2015, respectively. Conclusions Although the overall notification rate of hepatitis B in Guangzhou decreased annually, it remained high. Further, in rural areas, the notification rate has been increasing, and effective measures should be taken to control hepatitis B infection in Guangzhou. …

Journal of Medical Virology, Accepted Article.

Abstract Introduction To monitor Sweden’s progress towards the WHO goal of eliminating viral hepatitis, we estimated the prevalence, notification rate, and liver-related morbidity and mortality for diagnosed hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 2015 and 2018. Methods We identified cases of hepatitis B and C within the National System for Notifiable Diseases and obtained data on treatment and whether the case was deceased or not. We calculated prevalence, notification rates per 100,000, and proportion of newly diagnosed cases of hepatitis with liver disease at the time of diagnosis, and proportion of all deceased cases who died from liver disease. We calculated Poisson 95% confidence intervals (CIs) around the notification rates and Wilson 95% CIs around prevalence and mortality estimates. Results In 2015 and 2018, the prevalence of diagnosed HBV infections was 0.20% [95% CI: 0.19–0.20] and 0.21% [0.20–0.21]. Notification rates per 100,000 for HBV infections were 13.02 [12.32–13.76] and 7.71 [7.18–8.27]. HBV liver-related morbidity was 2.65% [1.90–3.68] and 2.16% [1.35–3.43]. HBV liver-related mortality was 20.00% [14.81–26.44] and 17.95% [13.20–23.94]. In 2015 and 2018, the prevalence of diagnosed HCV-infections was 0.24% [0.24–0.25] and 0.18% [0.18–0.19]. Notification rates per 100,000 for HCV infections were 15.92 [15.14–16.73] and 13.05 [12.36–13.77]. HCV liver–related morbidity was 8.14% [6.89–9.60] and 3.90% [2.99–5.08]. HCV liver–related mortality was 27.08% [24.54–29.77] and 26.90% [24.12–29.88]. Conclusions All indicators decreased or remained stable between 2015 and 2018, indicating progress in the elimination of viral hepatitis, especially for HCV infection. …

EDITORIAL…

ObjectivesEliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is central to WHO’s target of reducing hepatitis B infection in children to <0.1% by 2030. While Nigeria accounts for 8.3% of the global burden, interventional studies on prevention of MTCT of HBV are hardly available. This study aimed to assess the impact of prevention of MTCT interventions on vertical transmission of HBV among pregnant women in Nigeria.DesignA prospective cohort study.SettingA University Teaching Hospitals Complex in Nigeria between 2015 and 2021.Participants10 866 pregnant women and their pre-existing children.InterventionsEligible pregnant women were screened for HBsAg using chromatographic immunoassay (Micropoint, USA). HbsAg-positive women had HBV serological assay done and their pre-existing children were screened. Women with HBV DNA ≥2 00 000 IU/mL and those positive for hepatitis B e-antigen (HBeAg) had 300 mg/day of Tenofovir Disoproxil Fumarate (TDF) in the third trimester. The newborns had hepatitis B vaccines and HB immunoglobulin (HBIG) administered, followed by testing for HBsAg at 9 months postnatally.Primary outcome measuresPrevalence of chronic hepatitis B infection in pregnancy, and the incidence of MTCT of HBV.ResultsOverall, 395 women had chronic HBV infection, giving a prevalence of 3.64%. Their mean age was 31.51±5.71 years, with a median parity of 1.2. Thirteen women (5.2%) were positive for HBeAg, seven (3.1%) of the 225 pre-existing hepatitis B-exposed children were HbsAg positive and 17 women had prenatal TDF. Overall, 376 women completed the study, with mean birth weight of 3.21±1.86 kg and perinatal mortality rate of 29.2/1000 births. Hepatitis Bvaccine-HBIG combination was administered to 260 newborns, while the others had hepatitis B vaccine alone. All the children tested negative to the HbsAg at 9 months.ConclusionEliminating MTCT of HBV infection through validated protocols in low and middle income countries with the highest burden of chronic HBV infections is feasible. National scale-up of such protocols is recommended.…

New England Journal of Medicine, Ahead of Print.

by Bayan Othman, Muna Barakat, Amin Omar, Amani Al-Rawashdeh, Yazan Qashou, Rafat Zrieq, Mohammad A. A. Al-Najjar

This study aimed to assess the knowledge, practices, and beliefs among the Jordanian population regarding hepatitis B virus (HBV) infection. A cross-sectional questionnaire was designed and used to recruit participants from October 5th through December 12th. Statistical analysis was conducted using SPSS. Descriptive statistical analysis was used to analyse the sociodemographic data, the Shapiro-Wilk test was used to assess the normality, Cronbach’s α was used to evaluate the reliability of the questionnaire and Point-biserial correlation was used to figure out whether there is an association between Score of knowledge and the dichotomous variables. A random sample of 432 participated in the study. The majority were females (n = 310, 71.8%), the mean age was 21 (42.0%) years,416 (96.3%) were urban inhabitants and most of them (n = 351, 81.3%) had bachelor’s degree. School/university (n = 280, 64.8%) were reported as a major source of information followed by TV/internet/social media 276 (63.9%). The total mean (± SD) of knowledge score regarding HBV infection symptoms, transmission modes and treatment was found 12.28 ± 3.2. Participants’ knowledge regarding symptoms including nausea, vomiting and loss of appetite was 73 (16.9%). More than 80% had good knowledge regarding the complications of HBV infection. Only 100 participant reported vaccination (23.1%) against the virus. Poor knowledge and low vaccination rate against HBV were found thus implementing comprehensive educational program for people highlighting the importance of vaccination against the virus is crucial.

Journal of Medical Virology, Accepted Article.

Abstract Background Hepatitis B virus (HBV) infection is a global public-health problem. Since the introduction of an effective vaccine, the epidemiology of HBV infection is changing. We aimed to estimate the prevalence of HBV infection in the Gulf Cooperation Council (GCC) region and delineate any variation in member-countries, special sub-groups, and over time. Methods This is a systematic review and meta-analysis to review studies of HBV prevalence in the GCC region. Databases were searched and all studies from inception to July 31st, 2021, were considered for inclusion. The pooled HBV prevalence was analyzed using the random-effect model after assessment for heterogeneity. True prevalence was adjusted using the Rogan-Gladen estimator. Pre-defined subgroup analysis was performed, and publication bias was assessed. Results Overall, 99 studies (n = 1,944,200 participants) met the inclusion criteria. The overall HBV apparent prevalence was 3.05% (95% CI 2.60, 3.52) and the true prevalence was 1.67% (95% CI 1.66, 1.68). The apparent prevalence varied between subgroups. Over time, the apparent prevalence of HBV infection has declined from 9.38% (95% CI 7.26, 11.74) before 1990 to 1.56% (95% CI 1.07, 2.12) during the period 2010 to 2020. Conclusion Over the last four decades the overall prevalence of HBV infection in the GCC region has decreased from high- to low-endemicity level. However, due to poor methodology of the included studies, further high-quality community-based studies are needed to obtain more precise estimate of HBV infection in this region. …

A major hurdle in the long-term treatment of chronic hepatitis B (CHB) patients is to maintain viral suppression in the absence of drug resistance. To date, no evidence of resistance to tenofovir disoproxil fumarate (TDF) has been observed. A cumulative evaluation of CHB patients who qualified for resistance surveillance over 8 years of TDF treatment was conducted. Patients in studies GS-US-174-0102 (HBeAg-) and GS-US-174-0103 (HBeAg+) were randomized 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF through year 8. Population sequencing of HBV pol/RT was attempted for all TDF-treated patients at baseline and, annually if viremic, at discontinuation, or with addition of emtricitabine. Overall, 88/641 (13.7%) patients qualified for sequence analysis at one or more time points. The percentage of patients qualifying for sequence analysis declined over time, from 9 to 11% in years 1-2 to <4% over years 3-8. Forty-one episodes of virologic breakthrough (VB) occurred throughout the study, with most (n=29, 70%) associated with nonadherence to study medication. Fifty-nine per cent of VB patients with an opportunity to resuppress HBV achieved HBV DNA resuppression. A minority of patients who qualified for sequencing had polymorphic (41/165, 24.8%) or conserved (17/165, 10.3%) site changes in pol/RT, with six patients developing lamivudine and/or ADV resistance-associated mutations. No accumulation of conserved site changes was detected. The long-term treatment of CHB with TDF monotherapy maintains effective suppression of HBV DNA through 8 years, with no evidence of TDF resistance or accumulation of conserved site changes.

In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.

Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections.

Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection.

The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.

Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin.

Patients with cirrhosis resulting from chronic hepatitis C virus (HCV) infection are at risk of life-threatening complications, but consistently achieve lower sustained virological response (SVR) than patients without cirrhosis, especially if treatment has previously failed. We assessed the efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir, with and without ribavirin.

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.

Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.

In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin.

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis.

All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment.

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.

A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare.

Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.

Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase.

The diagnosis and treatment of hepatocellular carcinoma (HCC) have witnessed major changes over the past decade. Until the early 1990s, HCC was a relatively rare malignancy, typically diagnosed at an advanced stage in a symptomatic patient, and there were no known effective palliative or therapeutic options. However, the rising incidence of HCC in several regions around the world coupled with emerging evidence for efficacy of screening in high-risk patients, liver transplantation as a curative option in select patients, ability to make definitive diagnosis using high-resolution imaging of the liver, less dependency on obtaining tissue diagnosis, and proven efficacy of transarterial chemoembolization and sorafenib as palliative therapy have improved the outlook for HCC patients. In this article, we present a summary of the most recent information on screening, diagnosis, staging, and different treatment modalities of HCC, as well as our recommended management approach.

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV).

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count 50 g/d), CD4 count ( PMID: 10498659

Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression.

Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.

We measured antibody (anti-HCV) to hepatitis C virus, which causes non-A, non-B hepatitis, by radioimmunoassay in prospectively followed transfusion recipients and their donors. Of 15 patients with chronic non-A, non-B hepatitis documented by liver biopsy, all seroconverted for the antibody; of 5 with acute resolving non-A, non-B hepatitis, 3 (60 percent) seroconverted. The development of anti-HCV was delayed (mean delay, 21.9 weeks after transfusion, or 15 weeks after the onset of clinical hepatitis) and took approximately one year in one patient. Antibody has persisted in 14 of the 15 patients with chronic disease (mean follow-up, greater than or equal to 6.9 years; maximum, greater than or equal to 12), but has disappeared in the 3 with acute resolving disease after a mean of 4.1 years. Anti-HCV was detected in samples of donor serum given to 14 (88 percent) of the 16 anti-HCV-positive patients for whom all donor samples were available. Only 33 percent of the anti-HCV-positive donors tested had an elevated serum concentration of alanine aminotransferase; 54 percent were positive for antibody to the hepatitis B core antigen (anti-HBc). We conclude that hepatitis C virus is the predominant agent of transfusion-associated non-A, non-B hepatitis and that screening of donors for anti-HCV could prevent the majority of cases of the disease. "Surrogate" assays for anti-HBc and alanine aminotransferase would have detected approximately half the anti-HCV-positive donors involved in the transmission of hepatitis that we identified.