THIS ARTICLE HAS BEEN RETRACTED: Haemodynamic derangement in human immunodeficiency virus‐infected patients with hepatitis C virus‐related cirrhosis: the role of bacterial translocation

Background and aims: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)‐infected patients with decompensated hepatitis C virus (HCV)‐related liver disease. Methods: Forty HIV/HCV co‐infected patients and 40 HCV mono‐infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide‐binding protein (LBP). Monocyte expression of toll‐like receptor 4 (TLR‐4), serum levels of interleukin (IL)‐6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients. Results: Serum levels of LBP, TLR‐4, IL‐6 and sTNFRI were significantly higher in HIV–HCV co‐infected and HCV mono‐infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL‐6. There were no significant differences between HIV/HCV co‐infected and HCV mono‐infected patients. Conclusions: Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL‐6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co‐infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono‐infected patients.     

Risk factors for hepatitis C virus infection in individuals infected with the HIV

BACKGROUND: Except for injecting drug use, other routes of transmission for hepatitis C virus among HIV-AIDS patients have not been consistently described, and risk estimates are often not adjusted for confounding factors. AIMS: To evaluate characteristics associated with hepatitis C virus infection in individuals infected with the HIV. PATIENTS: Cases were patients co-infected by HIV and hepatitis C virus, and controls were infected only by HIV. METHODS: Cases and controls were consecutively enrolled at a public health care outpatient HIV-AIDS reference centre in Porto Alegre, Southern Brazil. RESULTS: A total of 227 cases (63% men; 40.3+/-8.7 years) and 370 controls (44.6% men; 38.9+/-9.8 years) were enrolled in the study. In a multiple logistic regression model, male gender (odds ratio 1.9; 95% confidence interval 1.3-2.7), age between 30 and 49 years (odds ratio 2.1; 95% confidence interval 1.2-3.7), elementary school education (odds ratio 4.2; 95% confidence interval 1.9-9.6), lower family income (odds ratio 1.7; 95% confidence interval 1.1-2.7), sharing personal hygiene objects (odds ratio 2.0; 95% confidence interval 1.3-3.3), using injected drugs (odds ratio 21.6; 95% confidence interval 10.8-43.0) and crack cocaine (odds ratio 2.8; 95% confidence interval 1.1-6.9) were independently associated with co-infection by hepatitis C virus. CONCLUSION: These results confirm the risk profile for hepatitis C virus-HIV infection and suggest that sharing personal hygiene objects might explain the transmission of virus C to those not infected by the usual routes, which may be of relevance for developing preventive strategies.     

Anti-hepatitis C virus treatment may prevent the progression of liver fibrosis in non-responder human immunodeficiency virus/hepatitis C virus coinfected patients

AimTo evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon + Ribavirine regimen.Materials and methodsWe investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon + Ribavirine treatment (Group hepatitis C virus Rx) administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated) after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula.ResultsLiver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16%) patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups.ConclusionLiver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy.     

Treatment of hepatitis C virus and human immunodeficiency virus coinfection: from large trials to real life

To analyse the barriers for anti-hepatitis C virus (anti-HCV) treatment in human immunodeficiency virus (HIV)-HCV coinfected patients, we surveyed 71 physicians specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS information and care (17%), haematology (10%) and hepatology (6%). A standard data collection form was used to identify patients observed in 7 days in November 2004. Three hundred and eighty patients with the following characteristics were included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago; routes of transmission via injection drug use (78%); undetectable HIV viral load (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of 369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been carried out in 56%. There were several explanations for the nontreatment of HCV in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti-HCV treatment was deemed questionable (n = 109) because of minor hepatic lesions, alcohol consumption, or active drug use; no liver biopsy had been performed (n = 68); treatment was contraindicated (n = 62), mainly for psychiatric reasons; there was physician conviction of poor patient compliance (n = 62) and patient refusal (n = 33). Patients having received anti-HCV treatment (n = 91) compared with those who had never received any (n = 205) were more commonly of European origin, had better control of their HIV infection, were followed by a hepatologist more often, had a liver biopsy more often and had more commonly a high HCV viral load (P < 0.001). In 'real life' in France in 2004, more than half of the HIV-HCV coinfected patients have never received anti-HCV treatment. The main reasons are a treatment that may be deemed questionable (minimal hepatic lesions, alcohol, active drug use), a lack of available liver biopsy, a psychiatric contraindication and physician conviction of poor patient compliance.     

Epidemiology of hepatitis C virus infection in HIV-infected individuals

Many individuals are infected with both HIV and hepatitis C virus (HCV) infection. More rapid progression of liver disease is seen, higher levels of HCV RNA encourage transmission and sustained virological responses are lower in coinfected patients. The management of these patients is further complicated by potential interactions between antiretroviral therapy and peginterferon and ribavirin.     

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus‐co‐infected patients in Myanmar

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight‐based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co‐infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro‐costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow‐up. SVR was achieved in 680/803 (84.6%) by intention‐to‐treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non‐PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real‐world estimate of $1250. High SVR rates were achieved for non‐PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real‐world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.     

Systemic manifestations and liver disease in patients with chronic hepatitis C and type II or III mixed cryoglobulinaemia

The aim of this study was to evaluate the prevalence of cryoglobulins in patients with chronic hepatitis B and C virus infection and to investigate the association of type II and type III mixed cryoglobulinaemia with systemic manifestations and liver disease stage and outcome in hepatitis C virus (HCV)-positive patients. We analysed the prevalence of cryoglobulinaemia in a cohort of patients with chronic liver disease and compared the systemic manifestations and liver involvement in HCV-positive patients with type II or type III mixed cryoglobulinaemia. The prevalence of serum cryoglobulins was significantly higher in HCV-positive patients than in hepatitis B surface antigen (HBsAg)-positive patients (55.4 vs 20.6%). In HCV-positive patients, stage of liver disease correlated with the prevalence of cryoglobulinaemia. Patients with type II cryoglobulins showed a significantly higher risk of cirrhosis and of extrahepatic manifestations while patients with type III cryoglobulins had a significantly higher prevalence of hepatocellular carcinoma. During follow-up the former had an odds ratio of 11.9 of death from extrahepatic complications while the latter had an odds ratio of 3.4 of dying from hepatic disease. Our study confirms the high frequency of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection. The presence and type of cryoglobulins seem to be associated with different clinical manifestations and outcome.     

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.     

Mortality in HIV‐infected injection drug users with active vs cleared hepatitis C virus‐infection: a population‐based cohort study

Summary. Acute hepatitis C virus (HCV) infection may lead to chronic HCV‐infection with detectable HCV RNA or to spontaneous clearance with no HCV RNA, but detectable HCV antibodies. It is unknown whether HCV RNA status is associated with mortality in HIV‐infected injection drug users (IDUs). We conducted a nationwide population‐based cohort study to examine the impact of HCV RNA status on overall and cause‐specific mortality in HIV‐infected IDUs. We computed cumulative mortality and used Cox Regression to estimate mortality rate ratios (MRR). We identified 392 HIV‐infected patients of whom 284 (72%) had chronic HCV‐infection (HCV RNA positive patients) and 108 (28%) had cleared the HCV‐infection (HCV RNA negative patients). During 1286 person‐years of observation (PYR), 157 persons died (MR = 122/1000 PYR, 95% CI: 104–143). The estimated 5‐year probabilities of survival were 0.58 (95% CI: 0.51–0.65) in the chronically HCV‐infected and 0.52 (95% CI: 0.40–0.63) in the cleared HCV group. Chronic HCV‐infection was not associated with overall mortality: MRR 0.85, 95% CI: 0.59–1.21. In HIV‐infected Danish IDUs, chronic HCV‐infection is not associated with increased mortality compared to patients who have cleared the infection.     

Correlates of high hepatitis C virus RNA load in a cohort of HIV‐negative and HIV‐positive individuals with haemophilia

Summary. Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV‐RNA load. Correlates of high HCV‐RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV‐infected individuals with haemophilia, we compared those with high (>2 × 10⁶ HCV‐RNA copies/mL) to lower viral load, overall and stratifying on HIV co‐infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P_trend = 0.0001), body mass index ≥25 kg/m² (OR = 1.4, 95% CI = 1.1–1.9), and HIV co‐infection (OR = 1.4, 95% CI = 1.0–1.8). Among 795 HIV‐negative participants, high HCV‐RNA load was associated with older age at HCV acquisition (OR = 1.9 for >15 years vs≤2 years, P_trend = 0.008), and lower AST/platelet ratio (P_trend = 0.01), in addition to longer duration of HCV infection (P_trend = 0.0008), and body mass index ≥25 kg/m² (OR = 1.6, P = 0.005). Among 471 HIV‐positive individuals, anti‐retroviral therapy (ART) was the only variable associated with high HCV‐RNA load (OR = 1.8, CI = 1.1–2.9 for combination ART; OR = 1.8, CI = 0.9–3.4, for other ART vs no treatment). High HCV‐RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end‐stage liver disease.     

Prevalence of coinfection with human immunodeficiency virus and hepatitis C virus in Japan

People with human immunodeficiency virus (HIV) infection are frequently infected with hepatitis C virus (HCV), because of the common transmission routes. Since the dissemination of hyperactive antiretrovirus therapy (HAART), the morbidity and mortality associated with HIV infection have declined. However, the reduction in mortality due to opportunistic infection has made HCV-associated liver diseases the leading cause of mortality in Western countries. A similar situation is assumed in Japan, but the status of coinfection with HIV and HCV is unclear. We conducted a nationwide survey to determine the prevalence of coinfection with HIV and HCV by distributing a questionnaire to the hospitals in the HIV/AIDS Network of Japan. Among 4877 patients reported to be HIV-positive, 935 (19.2%) were also positive for the anti-HCV antibody. Most (84.1%) of the patients coinfected with HIV and HCV were recipients of blood products. These data, for the first time, show the current status of coinfection with HIV and HCV in Japan. A detailed analysis of the progression and severity of liver diseases in the coinfected patients is expected.     

Phylogenetic analysis of acute hepatitis C virus genotype 4 infections among human immunodeficiency virus‐positive men who have sex with men in Germany

Background: An ongoing HCV epidemic currently affects a growing proportion of HIV‐positive men who have sex with men (MSM) in Europe. Recently in the North‐Rhine region of Germany, we have observed an increase in acute HCV infections of genotype 4 (HCV‐4). Aims: To characterize the current spread of HCV‐4 among German MSM using a molecular epidemiological approach. Methods: Patient characteristics and sera were collected for HIV‐positive MSM diagnosed with acute HCV‐4 infections in the North‐Rhine region (n=14), Hamburg (n=14), Frankfurt (n=4) and Berlin (n=4). Part of the HCV NS5B region (436 bp) was amplified, sequenced and compared with HCV‐4 sequences from HIV‐positive Dutch, English and French MSM (n=50) as well as unrelated HCV risk groups (n=61). Results: NS5B sequences were obtained from 35/36 (97%) of German cases, all of which were HCV subtype 4d (HCV‐4d). The phylogenetic analysis of HCV sequences revealed two MSM‐specific HCV‐4d clusters of 71 and 12 sequences. All except one of the German MSM belonged to a large MSM‐specific HCV cluster containing MSM from all four different European countries. None of the HCV‐4 strains circulating among injecting drug users or in HCV‐4 endemic areas were part of the MSM‐specific clusters. Conclusions: HCV rapidly spreads among European HIV‐positive MSM through a joint international transmission network, separate from that of injecting drug users. In order to contain this epidemic, non‐parenteral routes of transmission, such as unsafe sex, must be taken into consideration and prevention measures should be refocused accordingly.     

Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review

The hepatitis C virus and human immunodeficiency virus share the same transmission routes, which makes co-infection an unfavorable condition for the natural history of both viral diseases. In this context, it should be highlighted that the knowledge of the extent of co-infection and associated risk factors is a vital tool for prevention and control over infectious diseases. The aim of this study was to review the literature, seeking to examine the prevalence of human immunodeficiency virus/hepatitis C virus co-infection reported in studies conducted in Brazil, and identify the main risk factors associated with co-infection.The electronic search was conducted in the Medline, Lilacs and SciELO databases. The following keywords were used: human immunodeficiency virus and Hepatitis C or hepatitis C virus and Brazil. The search led to 376 articles, of which 69 were selected for data extraction. We excluded animal studies, reports or case series, review articles, letters to the editor, other types of hepatitis and those studies in which co-infected patients were intentionally selected for comparison to single infected individuals. As a result, 40 articles were reviewed. The majority of the population in these studies was male (71%) and young adults, with a mean age of 26.7 years. The prevalence of hepatitis C virus co-infection among individuals living with human immunodeficiency virus in the studies conducted in Brazil ranged from 3.3% (serum samples) to 82.4% (drug users), with an average of 20.3%. The findings reveal that the prevalence of human immunodeficiency virus/hepatitis C virus co-infection is highly variable, depending on the characteristics of the study population. Risk factors associated with human immunodeficiency virus/hepatitis C virus co-infection were injection drug use and blood transfusion.     

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

Summary. In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57=75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

Patients co-infected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA

Serum and liver hepatitis C virus (HCV) RNA levels in patients with hepatitis C have previously been quantified using different techniques. In this work, we used an automated, multicycle, polymerase chain reaction (PCR)-based technique to quantify HCV RNA in 1-2 mm of frozen liver tissue, and in serum, from 70 patients with antibodies to HCV (anti-HCV), with and without human immunodeficiency virus (HIV) co-infection. Stored liver tissue and sera collected at the time of liver biopsy were used for measurement of HCV RNA. Forty-eight HCV patients and 22 HIV/HCV co-infected patients were studied. Co-infected patients had significantly higher median serum and liver HCV RNA (6.7 log copies ml-1 serum and 2.90 log copies microg-1 liver nucleic acids) than patients with HCV alone (6.2 log copies ml-1 serum and 2.19 log copies microg-1 liver nucleic acids). There was only a weak correlation between serum and liver HCV RNA (r = 0.43). There was no correlation between liver and serum HCV RNA and host factors such as duration of disease, CD4 counts, alanine aminotransferase levels or histological score. There was no correlation with HCV genotype. Co-infected patients were more likely to harbour HCV genotype 1 (85%) when compared to patients with HCV alone (58%). An identical genotype was found in liver and serum in 89% of those tested; in 11%, a mixed genotype was present in serum. Patients with HCV genotypes 1 and non-1 had similar histological scores. Hence, an automated PCR-based technique is useful for measuring both liver and serum HCV RNA. Serum HCV genotypes closely paralleled those found in liver tissue. HIV co-infection was associated with higher serum, as well as intrahepatic, HCV RNA levels, by mechanisms not directly related to CD4 counts. The lack of correlation between liver HCV RNA and histology suggests that HCV is not directly cytopathic.