Predictors of liver fibrosis were evaluated in women using a noninvasive index (FIB-4). HIV RNA levels were associated with increased FIB-4 in the absence of viral hepatitis, alcohol use, or antiretroviral therapy. These data complement evidence suggesting a potential relationship between HIV infection and hepatic fibrosis.
Background. FIB-4 represents a noninvasive, composite index that is a validated measure of hepatic fibrosis, which is an important indicator of liver disease. To date, there are limited data regarding hepatic fibrosis in women.
Methods. FIB-4 was evaluated in a cohort of 1227 women, and associations were evaluated in univariate and multivariate regression models among 4 groups of subjects classified by their human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection status.
Results. The median FIB-4 scores were 0.60 in HIV-/HCV- women, 0.83 in HIV-/HCV+ women, 0.86 in HIV+/HCV- women, and 1.30 in HIV+/HCV+ women. In the HIV/HCV co-infected group, multivariate analysis showed that CD4+ cell count and albumin level were negatively associated with FIB-4 (P <.0001), whereas antiretroviral therapy (ART) was positively associated with FIB-4 score (P =.0008). For the HIV mono-infected group, multivariate analysis showed that CD4+ cell count (P <.0001) and albumin level (P =.0019) were negatively correlated with FIB-4 score, ART was positively associated with FIB-4 score (P =.0008), and plasma HIV RNA level was marginally associated with FIB-4 score (P =.080). In 72 HIV mono-infected women who were also hepatitis B surface antigen negative, ART naive, and reported no recent alcohol intake, plasma HIV RNA level was associated with increased FIB-4 score (P =.030).
Conclusions. HIV RNA level was associated with increased FIB-4 score in the absence of hepatitis B, hepatitis C, ART, or alcohol use, suggesting a potential relationship between HIV infection and hepatic fibrosis in vivo. A better understanding of the various demographic and virologic variables that contribute to hepatic fibrosis may lead to more effective treatment of HIV infection and its co-morbid conditions.
Objectives: To compare the rate of hepatic fibrosis progression in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients, and to identify factors that may influence fibrosis progression.
Patients and methods: A total of 153 HCV infected and 55 HCV-HIV coinfected patients were identified from two London hospitals. Eligible patients had known dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver biopsy, which was graded using the Ishak score. Univariate and multivariate logistic regression analyses were used to identify factors associated with fibrosis progression rate and the development of advanced fibrosis (stages 3 and 4).
Results: The estimated median fibrosis progression rate was 0.17 units/year (interquartile range (IQR) 0.10–0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07–0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy were all independently associated with more rapid fibrosis progression. ALT was correlated with histological index (r=0.35, p<0.001). A CD4 cell count ⩽250×106/l was independently associated with advanced liver fibrosis (odds ratio 5.36 (95% confidence interval 1.26–22.79)) and was also correlated with a higher histological index (r=−0.42, p=0.002).
Conclusion: HIV infection modifies the natural history of HCV by accelerating the rate of fibrosis progression by 1.4 fold, and the development of advanced fibrosis threefold. A low CD4 cell count was independently associated with advanced disease and correlated with higher histological index, which suggests that early antiretroviral therapy may be of benefit in slowing HCV progression in coinfected patients.
human immunodeficiency virus; liver fibrosis; hepatitis C virus
To characterize predictors of isolated hepatitis B core antibody (anti-HBc) among human immunodeficiency virus (HIV)–infected and HIV-uninfected women, we compared 702 women with anti-HBc and hepatitis B surface antibody (anti-HBs) with 490 women with isolated anti-HBc (1.8% of whom had detectable hepatitis B virus [HBV] DNA). Factors independently associated with isolated anti-HBc without viremia were detectable hepatitis C virus (HCV) RNA, HIV positivity, history of injection drug use, >10 lifetime sex partners, and HIV RNA level >100,000 copies/mL. Anti-HBs levels were lower among anti-HCV–positive women. Isolated anti-HBc was rarely explained by occult HBV in this cohort but may be explained by the influence of viral coinfections on anti-HBs level or durability.
Background & Aims
Prior studies suggest the rate of liver fibrosis progression is slower in African-Americans (AA) than Caucasian-Americans (CA) with chronic hepatitis C virus (HCV) infection.
Using a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use.
The distribution of Ishak fibrosis stages were 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%) and 5/6 (6.3%), and was similar in AA and CA (p= 0.22). After adjusting for biopsy adequacy, AA had a 10% lower rate of fibrosis progression than did CA, but the difference was not statistically significant (hazard ratio = 0.90, 95% confidence intervals = 0.72, 1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4 and 5/6 were 59.3%, 28.8% and 4.7%. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort, and 74 and 83 years for CA and AA, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score.
The rates of fibrosis progression were slow and did not appear to differ substantially between AA and CA.
AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions.
METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCV-RNA were included. Markers of fibrosis progression were assessed.
RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and 4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) > 25. Fibrosis progression correlated with the time interval between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression (P = 0.003). Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI > 25 and the time interval between 2 biopsies.
CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI > 25.
Hepatitis C virus; Liver fibrosis; Liver biopsy; Alanine-transaminase; Body mass index
Substance abuse remains one of the major threats to adolescent health in Western cultures. The study aim was to ascertain the extent of association between pubertal development and early adolescent substance use.
The design was a cross-sectional survey of 10- to 15-year-old subjects in the states of Washington, United States, and Victoria, Australia. Participants were 5769 students in grades 5, 7, and 9, drawn as a 2-stage cluster sample in each state, and the questionnaire was completed in the school classrooms. The main outcomes of the study were lifetime substance use (tobacco use, having been drunk, or cannabis use), recent substance use (tobacco, alcohol, or cannabis use in the previous month), and substance abuse (daily smoking, any binge drinking, drinking at least weekly, or cannabis use at least weekly).
The odds of lifetime substance use were almost twofold higher (odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.4-2.1) in midpuberty (Tanner stage III) and were threefold higher (OR: 3.1; 95% CI: 2.4-4.2) in late puberty (Tanner stage IV/V), after adjustment for age and school grade level. Recent substance use was moderately higher (OR: 1.4; 95% CI: 1.0-1.9) in midpuberty and more than twofold higher (OR: 2.3; 95% CI: 1.7-3.3) in late puberty. The odds of substance abuse were twofold higher (OR: 2.0; 95% CI: 1.2-3.2) in midpuberty and more than threefold higher (OR: 3.5; 95% CI: 2.2-5.4) in late puberty. Reporting most friends as substance users was more likely in the later stages of pubertal development, a relationship that accounted in part for the association found between later pubertal stage and substance abuse.
Pubertal stage was associated with higher rates of substance use and abuse independent of age and school grade level. Early maturers had higher levels of substance use because they entered the risk period at an earlier point than did late maturers. The study findings support prevention strategies and policies that decrease recreational substance use within the peer social group in the early teens.
puberty; substance abuse; smoking; alcohol consumption; cannabis; adolescence
Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.
Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3–4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1–1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52–72 weeks (from time of viral response +48 weeks) (group B, n = 31).
Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8–12 weeks, and late virologic response from 16–24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.
Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.
Consensus interferon; Hepatitis C; Ribavirin; Veterans Affairs
To measure Hepatitis C Virus (HCV) prevalence, incidence, and initiation of HCV therapy in a representative HIV-infected cohort of the urban poor.
The Research and Access to Care for the Homeless (REACH) Cohort is a systematic sample of HIV-infected marginally housed individuals identified from single-room occupancy hotels, homeless shelters, and free lunch programs in San Francisco.
Two hundred forty-nine participants with 28.9 months (median) of follow-up were studied. Mean age was 44 (range 24 to 75, standard deviation 8.4) years. Eighty-two percent were male, 43% were African-American, 64% were lifetime injection drug users, and 24% had been on the street or in a shelter in the prior month.
We measured HCV testing and treatment history with structured interviews; additionally, participants were tested for HCV antibodies (EIA-2) with RNA viral load confirmation.
At baseline, 172 (69.1%) were HCV-positive and 182 (73.1%) were HCV-positive at follow-up, including 155 (62.2%) with viremia. HCV-positive status was associated with having injected drugs, elevated serum alanine aminotransferase, homelessness in the last 1 year, and more severe depressive symptoms. The incidence of new HCV infection was 4.63% per person-year (ppy; 95% confidence interval, 2.31 to 8.13) in the entire cohort and 16.77% ppy among injection drug users. The prevalence of HCV antibody-negative HCV-viremia was 13.2% (10/76). Nonwhites were less likely to receive HCV testing and subspecialty referral, controlled for drug use and other confounders. Sixty-eight percent (123/182) were aware treatment was available; however, only 3.8% (7/182) or 1.16% ppy received HCV treatment.
While HCV infection is common, HCV treatment is rare in the HIV-HCV coinfected urban poor. Urban poor, nonwhite individuals are less likely to receive HCV testing and subspecialty referral than their white counterparts. Antibody-negative infection may complicate screening and diagnosis in HIV-infected persons.
hepatitis C; HIV infection; HIV/HCV coinfection; HCV treatment; homelessness
Interleukin (IL)-18 plays an important dual role in Th1 polarization and viral clearance, as well as in the development of liver fibrosis. Single-nucleotide promoter polymorphisms influence the transcription of IL-18 mRNA. Promoter polymorphisms are linked to delayed virus clearance and disease susceptibility in many diseases. However, there is no information about their role in hepatitis C virus (HCV) infection.
To investigate the association between −607 or −137 polymorphism with susceptibility and severity of HCV infection.
Patients and methods
Two hundred and four serologically proven patients with chronic HCV infection and 350 matched healthy controls were included in this study. Patients were segregated in 2 groups: group A with mild liver disease and group B with severe liver disease on the basis of histological activity index (HAI ≤5 or >5) and hepatic fibrosis score (≤2 or >2). IL-18 promoter genotyping was performed with sequence-specific primers.
There was no significant difference in the frequencies of −607 and −137 allelic distribution in patients and controls. The −607 A/A allele was more common in group A patients with mild liver disease than in patients with severe liver disease on the basis of HAI (38.6% vs. 21%, P = 0.05; odds ratio [OR] = 0.424, confidence interval [CI] = 0.233–0.773; R2 = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134–0.596; R2 = 0.434).
IL-18 promoter polymorphism at −607 position with A/A allele is a potential protective marker, as it is associated with milder liver disease in patients with chronic HCV infection.
IL-18; Hepatitis C; Polymorphism; HAI; Fibrosis
AIM: To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort.
METHODS: The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIV-infected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years, and a total of 69 487 person-years, between 1998 and 2004. ASD collected data on the presentation, treatment, and outcomes of HIV, including liver disease, hepatitis screening, and hepatitis diagnoses.
RESULTS: Incident liver disease, chronic hepatitis B virus (HBV), and hepatitis C virus (HCV) were diagnosed in 0.9, 1.8, and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV, screening and vaccination were not universally conducted or, if conducted, not documented.
CONCLUSION: Due to high rates of incident liver disease, viral hepatitis screening, vaccination, and treatment among HIV-infected individuals should be a priority.
Human immunodeficiency virus; Hepatitis B; Hepatitis C; Liver disease
Steatosis is common in hepatitis C virus (HCV)-infected patients and likely accelerates fibrosis progression. Leptin, the peptide product of the obesity gene (ob), has been implicated in hepatic fibrogenesis; circulating levels of leptin correlate with body fat mass. The objective of the present study was to determine the clinical and histological correlates of serum leptin in HCV-infected patients, and to determine its utility in predicting liver histological lesions.
PATIENTS AND METHODS:
In 62 patients with chronic HCV, serum leptin was measured using a commercially available immunoassay. Associations between leptin, metabolic parameters, and severe hepatic fibrosis (stages 2 to 4) and steatosis (30% or greater) were determined. The utility of leptin in predicting liver histology was determined using receiver operating characteristic (ROC) curves.
The median body mass index (BMI) was 23.2 kg/m2 (range 17.7 kg/m2 to 35.6 kg/m2); 16% of patients (n=10) had HCV genotype 3. Severe fibrosis and steatosis were present in 23% and 13% of patients, respectively. Leptin was strongly correlated with the BMI, and its levels were higher in women. BMI-corrected leptin levels were not independently associated with severe fibrosis but were significantly associated with steatosis (OR of 1.07; 95% CI 1.01 to 1.04). On it own, leptin was poorly predictive of severe steatosis (area under the ROC curve was 0.64; 95% CI 0.42 to 0.87). However, its accuracy improved with the addition of HCV genotype (area under the ROC curve was 0.86; 95% CI 0.72 to 1.00; P=0.07).
As observed in the non-HCV setting, serum leptin correlates with BMI; higher leptin levels are found in women than men with chronic HCV. Serum leptin is a poor predictor of HCV-related fibrosis but may play a role in predicting steatosis when combined with HCV genotype.
Fibrosis; Hepatitis; Leptin; Noninvasive; Prediction; Steatosis
Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PNALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PNALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PNALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PNALT have asymptomatic or nonspecific symptoms. HCV carriers with PNALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels.
Hepatitis C; Alanine Transaminase; Clinical Protocols; Liver Cirrhosis
Background and Aims
Fibrosis progression might be accelerated in patients that are co-infected with HIV and hepatitis C virus (HIV/HCV). However, no studies have directly compared fibrosis progression by paired liver biopsy between patients infected with HIV and HCV vs. those infected with only HCV.
Liver biopsy samples were collected from patients with HIV/HCV (n=306) and those with HCV; biopsies from 59 without a sustained virologic response (SVR) or cirrhosis were matched with those from patients with only HCV (controls) for initial fibrosis stage, demographics, and HCV treatment. For HIV/HCV patients, categorical variables at baseline and the area under the curve of continuous variables per unit time were analyzed for associations with fibrosis progression.
Liver biopsies from HIV/HCV patients had more piecemeal necrosis than controls (P=.001) and increased lobular inflammation (P=.002); HIV/HCV patients also had shorter intervals between liver biopsies (4.7 vs. 5.9 yrs, P<.0001). Between the 1st and 2nd biopsies, fibrosis remained unchanged or progressed 1 or 2 units in 55%, 18%, and 18% of HIV/HCV patients, respectively, compared with 45%, 30%, and 9% of controls. The fibrosis progression rate was similar between HIV/HCV and control patients (0.12±0.40 vs. 0.091±0.29 units/yr; P=.72). In paired biopsies from 66 patients, including those with SVR, there were no associations between fibrosis progression and demographics; numbers of CD4+ T cells; levels of aspartate aminotransferase or alanine aminotransferase; use of highly-active anti-retroviral therapy; response to HCV therapy (no treatment, SVR, or non-response); baseline levels of FIB-4; or histological features including inflammation, fibrosis, or steatosis.
Based on analysis of liver biopsy samples, fibrosis progression was similar between HIV/HCV- and HCV-infected patients; no clinical or laboratory parameters predicted disease progression.
Hepatitis C disease progression; co-infection; human immunodeficiency virus
Background. Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection.
Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV)–seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively.
Results. DQB1*0301 was associated with low baseline HCV load (β = −.4; 95% confidence interval [CI], −.6 to −.3; P < .00001), as well as with low odds of FIB-4–defined (odds ratio [OR], .5; 95% CI, .2–.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3–1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0–3.7; P = .04).
Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
Background and Aims
To compare several non-invasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection (platelet count, the APRI score, the Forns score, the Lok score, FIB-4, Transient Elastography [TE]), versus percutaneous liver biopsy (LB).
Our study included 150 patients with chronic HCV infection in which LB, liver stiffness measurement (LSM) by means of TE and biological tests needed for calculating the scores (according to the classic formulas) were performed in the same session.
The best test for predicting significant fibrosis (F = 2 Metavir) was LSM with AUROC-0.773, followed by APRI (AUROC-0.763), Forns (AUROC-0.744), platelet count (AUROC-0.732), Lok (AUROC-0.701) and FIB-4 (AUROC-0.669), but the differences were not statistically significant (P > 0.05). For excluding cirrhosis, all the tests had excellent NPV (>97%). The best test for predicting cirrhosis was LSM (AUROC-0.979), significantly better than platelet count (AUROC- 0.899, P = 0.022) and than FIB-4 (AUROC-0.839, P = 0.042), otherwise the differences were not statistically significant (P > 0.05). All of the non-invasive tests were statistically significantly correlated (P < 0.0001) to the severity of fibrosis: APRI r=0.570; Forns r=0.540; Lok r=0.4843; FIB-4 r=0.4171; platelet count r=-0.4842.
LSM by means of TE seems to be more sensitive than APRI, Forns, Lok and FIB-4 scores and than platelet count for the prediction of significant fibrosis, but the differences are not statistically significant. The APRI score and Forns scores correctly identified most (71%) of the patients having, or not having, significant fibrosis. LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (AUROCs 0.839-0.979).
Chronic Hepatitis C; Fibrosis; Liver Function Tests
Background: The natural history of hepatitis C virus (HCV) infection remains uncertain. Previous data concerning rates of progression are from studies using estimated dates of infection and single liver biopsy scores. We prospectively studied the rate of progression of fibrosis in HCV infected patients by repeat liver biopsies without intervening treatment.
Patients: We studied 214 HCV infected patients (126 male; median age 36 years (range 5–8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease. Interbiopsy interval was a median of 2.5 years. Paired biopsies from the same patient were scored by the same pathologist.
Results: Seventy of 219 (33%) patients showed progression of at least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points. Independent predictors of progression were age at first biopsy and any fibrosis on first biopsy. Factors not associated with progression were: necroinflammation, duration of infection, alcohol consumption, alanine aminotransferase levels, current or past hepatitis B virus infection, ferritin, HCV genotype, and steatosis or iron deposition in the initial biopsy.
Conclusions: One third of patients with predominantly mild hepatitis C showed significant fibrosis progression over a median period of 30 months. Histologically, mild hepatitis C is a progressive disease. The overall rate of fibrosis progression in patients with hepatitis C was low but increased in patients who were older or had fibrosis on their index biopsy. These data suggest that HCV infection will place an increasing burden on health care services in the next 20 years.
hepatitis C virus; fibrosis; hepatic fibrosis
3,537 men enrolling in 2007 for mandatory army recruitment procedures were assessed for the co-occurrence of risky licit substance use among risky cannabis users. Risky cannabis use was defined as at least twice weekly; risky alcohol use as 6+ drinks more than once/monthly, or more than 20 drinks per week; and risky tobacco use as daily smoking. Ninety-five percent of all risky cannabis users reported other risky use. They began using cannabis earlier than did non-risky users, but age of onset was unrelated to other risky substance use. A pressing public health issue among cannabis users stems from risky licit substance use warranting preventive efforts within this age group.
risky cannabis use; co-occurring risky licit substance use; early onset; Switzerland
Background—A novel flavivirus has been described
recently and designated hepatitis G virus (HGV). The virus is
transmitted by the parenteral route but it is uncertain whether it is
associated with chronic liver disease because liver biopsy is difficult
to justify in this group.
Aims—To examine histological features of liver
biopsy in patients infected with hepatitis C virus (HCV) according to
the presence or absence of HCV and HGV RNA.
Methods—One hundred and thirty one consecutive
HCV carriers undergoing staging liver biopsy were studied
retrospectively. In each, HCV RNA and HGV RNA were detected by reverse
transcription polymerase chain reaction on serum samples collected at
the time of biopsy. The presence of each RNA was correlated with
histological features blind to the RNA results; individual histological
features of inflammation or fibrosis were scored separately.
Results—Nineteen patients were positive for both
HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were
positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not
statistically significant. There was no effect of HGV coinfection on
the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for
fat than those patients with HCV RNA alone (p<0.05).
Conclusions—HGV coinfection has no important
effects on histological features in chronic HCV carriers. It is
unlikely that HGV infection causes chronic liver disease.
hepatitis C virus; hepatitis G virus; RNA; histology
The impact of co-morbid substance use in first-episode schizophrenia has not
been fully explored.
This naturalistic follow-up of a cohort of 152 people with first-episode
schizophrenia examined substance use and clinical outcome in terms of
symptoms and social and neuropsychological function.
Data were collected on 85 (56%) of the patient cohort after a median period
of 14 months. Over the follow-up period, the proportion of smokers rose from
60% at baseline to 64%. While 30% reported lifetime problem drinking of
alcohol at baseline, only 15% had problem drinking at follow-up.
Furthermore, while at baseline 63% reported lifetime cannabis use and 32%
were currently using the drug, by the follow-up assessment the latter figure
had fallen to 18.5%. At follow-up, persistent substance users had
significantly more severe positive and depressive symptoms and greater
overall severity of illness. A report of no lifetime substance use at
baseline was associated with greater improvement in spatial working memory
(SWM) at follow-up.
Past substance use may impede recovery of SWM performance in people with
schizophrenia in the year or so following first presentation to psychiatric
services. The prevalence of substance use other than tobacco tends to
diminish over this period, in the absence of specific interventions.
Persistent substance use in first-episode schizophrenia is associated with
more severe positive and depressive symptoms but not negative symptoms, and
should be a target for specific treatment intervention.
Substance use; schizophrenia; first-episode
The impact of co-morbid substance use in first-episode schizophrenia has not been fully explored.
This naturalistic follow-up of a cohort of 152 people with first-episode schizophrenia examined substance use and clinical outcome in terms of symptoms and social and neuropsychological function.
Data were collected on 85 (56%) of the patient cohort after a median period of 14 months. Over the follow-up period, the proportion of smokers rose from 60% at baseline to 64%. While 30% reported lifetime problem drinking of alcohol at baseline, only 15% had problem drinking at follow-up. Furthermore, while at baseline 63% reported lifetime cannabis use and 32% were currently using the drug, by the follow-up assessment the latter figure had fallen to 18.5%. At follow-up, persistent substance users had significantly more severe positive and depressive symptoms and greater overall severity of illness. A report of no lifetime substance use at baseline was associated with greater improvement in spatial working memory (SWM) at follow-up.
Past substance use may impede recovery of SWM performance in people with schizophrenia in the year or so following first presentation to psychiatric services. The prevalence of substance use other than tobacco tends to diminish over this period, in the absence of specific interventions. Persistent substance use in first-episode schizophrenia is associated with more severe positive and depressive symptoms but not negative symptoms, and should be a target for specific treatment intervention.
First-episode; schizophrenia; substance use
Increased hepatic iron is assumed to potentiate progression towards liver fibrosis in chronic hepatitis C virus (HCV) infection. In this study we have evaluated the potentiating effect of marked hepatic iron overload and chronic HCV infection on hepatic fibrosis in thalassemic patients.
Liver biopsies of one group of patients with beta thalassemia major and chronic HCV infection (group 1) was compared with two groups of patients (groups 2&3) with either chronic HCV infection or thalassemia major, respectively (20 patients in each group). Necroinflammation, fibrosis, and iron overload were graded and compared.
Stage of fibrosis in group 1 patients was significantly higher than the other two groups (p < 0.05). Necroinflammatory grade was significantly lower, but iron score was significantly higher in thalassemic patients (group 3) in comparison to groups 1 and 2 (p < 0.05).
Our results indicate that marked liver iron overload and HCV infection in thalassemic patients have potentiating effect on hepatic fibrogenesis.
CXCL9 (monokine induced by IFN γ [Mig]) and CXCL10 (interferon [IFN] γ−inducible protein 10 [IP-10]) have been associated with hepatic fibrosis in predominantly white hepatitis C virus (HCV)–infected patients. We investigated their potential as noninvasive markers of hepatic fibrosis and fibrosis progression in African-American patients. Peripheral chemokine levels were measured in 115 HCV-infected patients within 4 months of liver biopsy; patients underwent a second biopsy after 3–5 years. CXCL10 levels appeared to be higher in patients with advanced fibrosis on the contemporaneous biopsy and were significantly higher in patients with advanced fibrosis compared with those with minimal fibrosis on the later biopsy (P = .0045). Therefore, CXCL10 has potential as a marker of fibrosis progression in African-American HCV-infected patients.
Background and aims: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer.
Materials and methods: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively. All were HCV RNA positive on polymerase chain reaction testing. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, untreated patients were divided into mild hepatitis (F ⩽2/6, NI ⩽3/18), moderate/severe hepatitis (3 ⩽F <6 or NI ⩾4), and cirrhosis (F = 6/6) groups. In addition, 20 age matched healthy volunteers were studied. After an overnight fast, a bolus of contrast agent (Levovist) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis. HVTTs were calculated as the time from injection to a sustained rise in Doppler signal >10% above baseline. The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times (CDT) calculated as the difference between carotid and hepatic vein arrival times. The earliest HVTT in each patient was used for analysis.
Results: Mean (SEM) HVTT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis groups showed a monotonic decrease of 38.1 (2.8), 38.8 (2.4), 26.0 (2.4), and 15.8 (0.8) seconds, respectively. Mean (SEM) CDT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis patients again showed progressive shortening of 30.3 (2.6), 25.9 (2.6), 14.8 (2.1), and 5.6 (1.2) seconds, respectively. There were significant differences between the groups for HVTT (ANOVA, p<0.001) and CDT (ANOVA, p<0.001). There was 100% sensitivity and 80% specificity for diagnosing cirrhosis and 95% sensitivity and 86% specificity for differentiating mild hepatitis from more severe liver disease.
Conclusion: We have shown, for the first time, that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis. There were significant differences between these two groups and the moderate/severe hepatitis group. CDT offers no additional benefit or greater differentiation than HVTT and can be omitted, thus simplifying this technique. HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy.
ultrasound; microbubbles; hepatitis C; liver; tracer studies; functional studies
Hepatitis C virus (HCV) is the major cause of liver disease in hemophilia. Few data exist on the proportion with liver fibrosis in this group after long-term HCV and HIV co-infection.
We conducted a cross-sectional multi-center study to determine impact of HIV on the prevalence and risk factors for fibrosis in hemophilic men with chronic hepatitis C.
Biopsies were independently scored by Ishak, Metavir, and Knodell systems. Variables were tested for associations with fibrosis by logistic regression and receiver operating curves (ROC).
Of 220 biopsied HCV(+) men, 23.6% had Metavir ≥F3 fibrosis, with higher mean Metavir fibrosis scores among HIV/HCV co-infected than HCV mono-infected, 1.6 vs. 1.3 (p=0.044). Variables significantly associated with fibrosis included AST, ALT, APRI score (AST/ULN×100/platelet ×109/L), alpha-fetoprotein (all p<0.0001), platelets (p=0.0003), and ferritin (p=0.0008). In multiple logistic regression of serum markers, alpha-fetoprotein, APRI, and ALT were significantly associated with ≥ F3 fibrosis, AUROC=0.77 (95%CI 0.69, 0.86). Alpha-fetoprotein, APRI, and ferritin were significant in HIV(−), (AUROC 0.82 (95%CI 0.72, 0.92), and alpha-fetoprotein and platelets in HIV(+) (AUROC=0.77 (95%CI 0.65, 0.88). In a multivariable model of demographic and clinical variables, transformed (natural logarithm) of alpha-fetoprotein (p=0.0003), age (p=0.006), and HCV treatment (p=0.027) were significantly associated with fibrosis.
Nearly one-fourth of hemophilic men have Metavir ≥ 3 fibrosis. The odds for developing fibrosis are increased in those with elevated alpha-fetoprotein, increasing age, and past HCV treatment.
Hepatitis C; Fibrosis; Hemophilia; Transfusion; Metavir; Receiver operating curve
In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.