Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

AIM: To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-four patients with chronic HCV infection were included in this study; 124 patients were non-cirrhotic, and 30 were cirrhotic. The following measurements were obtained in all patients: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, prothrombin time and concentration, complete blood count, hepatitis B surface antigen (HBsAg), HCVAb, HCV-RNA by quantitative polymerase chain reaction, abdominal ultrasound and ultrasonic-guided liver biopsy. The following ratios, scores and indices were calculated and compared with the results of the histopathological examination: AST/ALT ratio (AAR), age platelet index (API), AST to platelet ratio index (APRI), cirrhosis discriminating score (CDS), Pohl score, G teborg University Cirrhosis Index (GUCI). RESULTS: AAR, APRI, API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%, 79.2%, 76.6% and 80.5%, respectively); P values were: < 0.01, < 0.05, < 0.001 and < 0.001, respectively. Among the studied parameters, AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5, respectively. APRI, API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P < 0.001, < 0.001 and < 0.005, respectively), while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P > 0.05). In addition, we found significant correlations for the AAR, APRI, API, GUCI and Pohl score between the non-cirrhotic (F0, F1, F2, F3) and cirrhotic (F4) groups (P values: < 0.001, < 0.05, < 0.001, < 0.001 and < 0.005, respectively; CDS did not demonstrate significant correlation (P > 0.05). CONCLUSION: The use of AAR, APRI, API, GUCI and Pohl score measurements may decrease the need for liver biopsies in diagnosing cirrhosis, especially in Egypt, where resources are limited.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-&#x003b1; inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications.HCV genotyping was done using INNO-LiPATM HCV in serum,PBMCs,and liver biopsy specimens and then conf irmed by sequencing of 5'-UTR fragments.RESULTS:The mean age of patients was 30.3 ± 17.1 years.Multiple transfusion was seen in 124(93.2%) of patients.Multiple HCV genotypes were found in 3(2.3%) of 133 plasma samples,9(6.8%) of 133 PBMC samples,and 8(18.2%) of 44 liver biopsy specimens.It is notable that the different genotypes found in PBMCs were not the same as those found in plasma and liver biopsy specimens.CONCLUSION:Our study shows that a signif icant proportion of patients with chronic hepatitis C are affected by multiple HCV genotypes which may not be detectable only in serum of patients.

Alcoholic hepatitis and concomitant hepatitis C virus infection

Hepatitis C virus(HCV)infection and alcohol abuse are two most important causes of chronic liver disease in the United States.Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality.About 20%of patients presenting with alcoholic hepatitis have concomitant HCV infection.Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage.Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection.The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.

Signal transduction pathways in liver and the influence of hepatitis C virus infection on their activities

In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the transforming growth factor β signal transduction pathway,the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction pathway.All of them are activated by many different cytokines and growth factors.They regulate specific cell mechanisms such as hepatocytes proliferation,growth,differentiation,adhesion,apoptosis,and synthesis and degradation of the extracellular matrix.The replication cycle of hepatitis C virus(HCV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its genes.Moreover,HCV itself,by its structural and non-structural proteins,could influence the activity of the second signal messengers.Thus,the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis C treatment.

Hepatitis C virus infection in the human immunodeficiency virus infected patient

Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both viruses.The majority of people acquire HCV by injection drug use and,to a lesser extent,through blood transfusion and blood products.Recently,there has been an increase in HCV infections among men who have sex with men.In the context of effective antiretroviral treatment,liver-related deaths are now more common than Acquired Immune Deficiency Syndromerelated deaths among HIV-HCV coinfected individuals.Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20%of chronically infected individuals.HCV treatment has rapidly changed with the development of new direct-acting antiviral agents;therefore,cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle.In this review,we focus on the epidemiology,diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.

Is chronic hepatitis C virus infection a risk factor for breast cancer?

AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group included female patients with other well documented chronic liver diseases:chronic hepatitis B,alcoholic liver disease,autoimmune hepatitis,hemochromatosis,non alcoholic liver disease,chronic cholangitis.Participating patients were prospectively questioned during consultation about past breast history and follow-up by mammography.RESULTS:Breast carcinoma was recorded in 17/294 patients with HCV infection(5.8%,95% CI:3.1-8.4) vs 5/107 control patients(4.7%,95% CI:0.67-8.67).Benign tumors of the breast(mastosis,nodules,cysts) were recorded in 75/294 patients with HCV infection(25.5%,95% CI:20.5-30.5) vs 21/107(19.6%,95% CI:12.1-27.1) in the control group.No lesion was noted in 202 patients with HCV(68.7%,95% CI:63.4-74) vs 81 control patients(75.7%,95% CI:67.6-83.8).Despite a trend to an increased prevalence in the group with HCV infection,the difference was not significant compared to the control group(P=NS).In patients over 40 years,the results were,respectively,as follows:breast cancer associated with HCV:17/266 patients(6.3%,95% CI:3.4-9.3) vs 5/95 patients(5.2%,95% CI:0.7-9.7) in the control group;benign breast tumors:72/266 patients with HCV infection(27%,95% CI:21.7-32.4) vs 18/95 patients(18.9%,95% CI:11-26.8) in the control group;no breast lesion 177/266(66.5%,95% CI:60.9-72.2) in patients with HCV infection vs 72/95(75.7%,95% CI:67.1-84.4) in the control group.The differences were not significant(P=NS).CONCLUSION:These results suggest that chronic HCV infection is not a strong promoter of breast carcinoma in adult females of any age.

Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan

BACKGROUND Little is known about the engagement in hepatitis C virus(HCV)care and completion of HCV treatment in people living with human immunodeficiency virus(HIV)(PLWH)who have HCV coinfection in the Asia-Pacific region.Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.METHODS PLWH with incident HCV infections,defined as HCV seroconversion,were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018.All PLWH with incident HCV infections were followed until December 31,2019.The care cascade of HCV examined included all incident HCV-infected patients,the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care,plasma HCV RNA load tested,HCV RNA positivity diagnosed,referral to treatment assessment made,anti-HCV treatment initiated,and sustained virologic response achieved.Those who had HCV seroconversion during the interferon(IFN)era(2011–2016)and the direct-acting antiviral(DAA)era(2017–2018)were analyzed separately.The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections(STIs)during the HCV viremic period were estimated.RESULTS During the study period,287 of 3495(8.2%)PLWH(92.3%being men who have sex with men)who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples.Of the 287 incident HCV infections,277(96.5%)had anti-HCV antibodies detected by HIV-treating physicians,270(94.1%)had plasma HCV RNA determined and 251(87.5%)tested positive for HCV RNA.Of those with HCV viremia,226(78.7%)were referred to treatment assessment,215(74.9%)initiated anti-HCV treatment,and 202(70.4%)achieved viral clearance.Compared with that in the IFN era,the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era{179 d[interquartile range(IQR)87-434]vs 92 d(IQR 57-173);P<0.001}.The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up(PYFU)and 38.5 per 100 PYFU,respectively,with an incidence rate ratio of 1.31(95%confidence interval 0.96-1.77),while the duration of HCV viremia was 380 d(IQR 274-554)and 735 d(IQR 391-1447)(P<0.001),respectively.CONCLUSION While anti-HCV therapies are effective in achieving viral clearance,our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

Occult hepatitis B infection(OBI), is characterized by low level hepatitis B virus(HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen(HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.

Comparative Assay of Hepatitis B and C Virus Infection Markers by Different Assay Kits^1

In order to compare sensitivity of EIA and RIA assay kits for hepatitis B and C virus (HBV and HCV, respectively) infection markers, 100 serum samples in total were collected form 50 adult women each in urban and rural areas in northeast China. The number of positive cases to the three infection markers on HBV (i.e., HBsAg +, anti HBs +, and anti HBc +) and the one on HCV (anti HCV +) were examined in two laboratories, i.e., in Laboratory A with EIA kits produced in China and in Laboratory B with RIA kits. HCV infection positivity (anti HCV +) was examined by EIA kits in both laboratories, but from different sources in and outside of China, respectively. The assay in Laboratory A gave 2 HBsAg + cases out of the 100 cases examined, whereas there were 9 positive cases in Laboratory B. In contrast, 19 cases were positive to anti HCV when examined in Laboratory A, and there were 3 cases in Laboratory B. Thus, the kits used in Laboratory A gave fewer HBsAg + and more anti HCV + cases than the kits used in Laboratory B. The prevalence of anti HBs + or anti HBc + and cases did not differ when assayed in the two laboratories with EIA and RIA kits, respectively. The agreement of positive and negative findings between the two sets of testing were 93%, 93%, 93%, 86% and 82% for HBsAg, anti HBs, anti HBc, HBV (i.e., either positive to anyone of the three markers or negative to all three markers), and anti HCV, respectively. The implication of the observation on epidemiology on HBV and HCV infection prevalence was discussed.

Hepatitis C virus associated glomerulopathies

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type&#x02005;I&#x02005;MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-&#x003b1; plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection

AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection.

Desperately seeking hepatitis C virus

Spanish investigators described recently the so-called occult hepatitis C virus (HCV) infection, emphasizing the detection of genomic and antigenomic HCV RNA strands in liver and peripheral blood mononuclear cells. Therefore, the persistence of viral replication in occult HCV infection should be considered as a putative source of infection among family members and patients undergoing invasive procedures, transfusion or transplantation. Additionally, the most worrisome finding is that an occult HCV infection may persist in patients with sustained virological response.

Monitoring hepatitis C virus treatment rates in an Opioid Treatment Program:A longitudinal study

BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.

Hepatitis C virus micro-elimination:Where do we stand?

Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemic ofthe coronavirus disease 2019. Consequently, the more realistic objective ofeliminating HCV from population segments for which targeted strategies ofprevention and treatment are easily attained has been promoted in Europe, as avalid alternative. The underlying idea is that micro-elimination will ultimatelylead to macro-elimination. The micro-elimination strategy may target differentspecific populations and at-risk groups. Different settings, including prisons andhospitals, have also been identified as micro-elimination scenarios. In addition,dedicated micro-elimination strategies have been designed that are tailored at thegeographical level according to HCV epidemiology and individual country’sincome. The main elements of a valid and successful micro-elimination project arereliable epidemiological data and active involvement of all the stakeholders.Community involvement represents another essential component for a successfulprogram.

Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

AIM： Before pegylated interferon alpha （IFN） was introduced for the therapy of chronic hepatitis C virus （HCV）-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS： Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 （n = 12） were treated for 24 wk, and patients with genotypes other than 2 or 3 （n = 34） for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment （EOT）. Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin （10 mg（kg·d）） additionally. RESULTS： During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients （n = 9） infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients （66.7%） were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed （33.3%）. In comparison, patients infected with genotypes other than 2 or 3 （n = 34） showed an initial virological response rate of only 23.5% （n = 8）, and even in combination with ribavirin a sustained virological response （SVR） rate of only 11.8% （n = 4） could be achieved. CONCLUSION： In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.