Therapy For Chronic Hepatitis C Research Articles

Assessment of body mass index in patients with chronic hepatitis C who received an effective antiviral therapy

To evaluate the body mass index (BMI) in patients with chronic hepatitis C (CHC) with different stages of liver fibrosis and steatosis who received effective antiviral therapy (AVT). The study included 278 CHC patients with a sustained virologic response (SVR) at the end of treatment. In addition to assessing the investigational data to determine the clinical status of the patient, we calculated BMI (following the World Health Organization guidelines) and determined the severity of liver fibrosis (F) and steatosis (S) using transient elastography. The patients were assessed at the start of antiviral therapy, after ≥6 months from the moment SVR was confirmed, and then every 12 to 24 months. By the end of the study, the mean patient age was 49 years, 53% of them were men, and 34% of the patients were obese. Excessive weight gain was registered in 17% (n=48) of the cases, with 60% newly diagnosed with Class 1 to 2 obesity. Both before the start of AVT and years after reaching SVR, the mean BMI corresponded to the reference pre-obesity values, the liver steatosis was significantly more often absent in normal BMI; on the contrary, fatty liver (predominantly S2 to S3) was registered in individuals with elevated BMI (p<0.0001). After the long-term period following a successful therapy, Stage F4 liver fibrosis patients were mainly diagnosed with obesity (80% versus 44% before AVT; p=0.0010). The high proportion of patients with elevated BMI and liver steatosis seen years after a successful CHC therapy indicates a continued risk of progression of chronic liver disease. Such patients should be advised on how important it is to change their lifestyle to reduce overweight and prevent weight gain. We also need long-term assessments of how liver steatosis changes over time and what are the outcomes associated with post-SVR increase in BMI.

Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up.

Chronic hepatitis C (CHC) management has changed tremendously after direct-acting antivirals (DAAs) availability. Sustained virological response (SVR) has improved significantly, but one of the major concerns is the chances of de novo hepatocellular carcinoma (HCC) development after DAAs. The objective of the study is to calculate the frequency of newly diagnosed cases of HCC after antiviral therapy for CHC in Pakistan. This prospective, interventional research was conducted from June 2017 to September 2020. All patients after antiviral therapy for CHC were followed with an ultrasound abdomen and α-fetoprotein, six monthly. Multiphasic computed tomography (CT) of the abdomen was performed in suspected cases. For quantitative variables, the mean and standard deviations were calculated, whereas the qualitative variables were analyzed by frequencies and percentages. Among 180 patients, 110 were men and 70 were women with a mean age of 45.52 ± 11.71 years. One hundred and twenty-six patients were noncirrhotic, 38 had compensated cirrhosis while 16 had decompensated cirrhosis. One hundred and sixty-four (91.11%) patients achieved SVR, of which 22 (12.22%) patients developed new HCC during follow-up. Compensated cirrhosis group had 10 patients, the decompensated group had 12 patients, and the noncirrhotic group had no new HCC cases. Among patients with the new HCC, 12 achieved SVR. The risk of the development of HCC after antiviral treatment is highly significant among patients with liver cirrhosis. So, a strict surveillance strategy should be adopted in every cirrhotic patient following treatment with DAA agents even if they achieve SVR. Chances of developing HCC are still significantly high even after achieving SVR with DAAs in patients with liver cirrhosis.Patients with liver cirrhosis should be under surveillance for HCC even after achieving SVR after DAAs treatment. Rasool S, Hanif S, Ahmad A, et al. Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up. Euroasian J Hepato-Gastroenterol 2022;12(2):73-76.

Profiling the physiological pitfalls of anti-hepatitis C direct-acting agents in budding yeast.

SummarySofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.

Противовирусная терапия хронического гепатита С: многолетний опыт реальной клинической практики

Direct-acting antivirals (DAAs) have significantly changed the treatment of chronic hepatitis C (CHC) and the prognosis for patients since their introduction into clinical practice in 2014–2015. Objective. Study of the evolution and efficacy of antiviral therapy (AVT) for CHC based on the results of providing medical care to patients in Moscow in 2002–2020. Patients and methods. The study was conducted in the Center for the Treatment of Chronic Viral Hepatitis “Infectious Clinical Hospital No 1 of the Moscow City Health Department”. For quantitative variables, the mean and standard deviation were used, while for categorical variables, frequency and proportion were counted (%). Results. 69,745 patients were diagnosed with CHC among all the patients who were examined in the Center. The pooled SVR rate of various therapy regimens was as follows in the HCV genotype 1 (GT1) cohort: IFN + ribavirin – 41.7%; DAAs + PegIFN + ribavirin – 77.4%; IFN-free regimens – 94.0%. Age older than 40 years, diabetes mellitus (DM), history of AVT failure (retreatment), and liver cirrhosis (LC) adversely affected the achievement of SVR. In the patients with HCV GT2 and GT3, the IFN + ribavirin combination allowed SVR achievement in 68.5% of patients, while IFN-free regimens were effective in 95.2% of patients. The predictive factors for achieving SVR were similar to those in the GT1 subgroup, except that the effect of age and DM did not reach statistical significance. Conclusions. The efficacy of DAAs in real clinical practice significantly exceeds the efficacy of IFN-based regimens in patients with various HCV infection genotypes. Achievement of SVR as a result of AVT reduces the likelihood of LC and HCC development. Key words: viral hepatitis, chronic hepatitis, antiviral therapy, peginterferon, interferon-free, dual therapy, triple therapy

Хронический гепатит С у детей с ВИЧ-инфекцией: особенности течения, успехи противовирусной терапии

Objective. To analyze the course of chronic hepatitis C (CHC) and efficacy of its treatment in children with HIV infection. Patients and methods. This study included 29 children aged 12 to 17 years (mean age 15.1 ± 0.2 years) with perinatal HIV infection and CHC. HIV stages were distributed as follows: stage 4A in 24 individuals (82.8%), stage 4B in 4 individuals (13.8%), and stage 4B in 1 individual (3.4%). All 29 patients received antiretroviral therapy. The distribution of children by HCV genotypes was as follows: 1a in one child (3.4%), 1b in 12 children (41.4%), and 3a in 16 children (55.2%). Antiviral therapy for CHC included glecaprevir/pibrentasvir (3 tablets; 100 mg + 40 mg) once a day for 56 days. Data analysis was performed using the Statistica for Windows software (version 10.0). Results. The mean HCV RNA level was 595,666 ± 34,734 IU/mL (range: 1,100–3,863,025 IU/mL). After 4, 8, or 12 weeks of antiviral therapy for HCV, HCV RNA clearance was achieved in all study participants (p = 0.01). Before treatment initiation, mean CD4+ count was 738 ± 34 cells/μL (above 500 cells/μL), which indicated the absence of immunodeficiency in the group analyzed. Successful antiviral therapy for HCV (sustained virologic response at week 12; SVR 12) also resulted in increase of the CD4+ lymphocytes level, which was considered as a positive effect of glecaprevir/pibrentasvir (p = 0.15). We observed significant differences in the level of liver enzymes (ALT and AST) (p = 0.01) between samples collected before antiviral therapy initiation and those collected during treatment, as well as 12 weeks after its completion (SVR12). All children demonstrated good tolerance of glecaprevir/pibrentasvir; none of them had adverse events, complaints, or clinical/laboratory changes. Conclusion. Thus, all children with HIV infection and CHC achieved SVR12 after the 8-week course of antiviral therapy with glecaprevir/pibrentasvir regardless of HCV genotype. Clinical manifestations (hepatosplenomegaly in 62.1%; asthenovegetative syndrome in 31.0%) were eliminated after 8 weeks of therapy. Laboratory manifestations (hepatic cytolysis (AST/ALT)) were normalized after 4 weeks of therapy. Antiviral treatment for HCV resulted in some increase in the level of CD4+ lymphocytes. We observed no adverse events caused by glecaprevir/pibrentasvir (neither clinical symptoms nor changes in complete blood count or liver function tests), which confirms the safety of this treatment regimen. Key words: antiretroviral therapy, HIV infection, children, direct-acting antivirals, chronic hepatitis C

Antiviral therapy against chronic hepatitis C is associated with a reduced risk of oral cancer.

To identify the risk factors of oral cancer, we investigated the association between chronic hepatitis C (CHC) and oral cancer, and the development of oral cancer after anti-hepatitis C virus (HCV) therapy. We conducted a nationwide, population-based cohort study from 2004 to 2012 from the Taiwan National Health Insurance Research Database. CHC patients without anti-HCV therapy were matched with those non-HCV patients by age, sex and comorbidities. Moreover, CHC patients who underwent pegylated interferon and ribavirin (PegIFN/RBV) anti-HCV therapy were matched with CHC patients without anti-HCV therapy. A total of 100,058 patients were included in the HCV cohort and non-HCV cohorts, respectively. Their mean age was 59 years and 50% of these were male. CHC infection significantly increased the cumulative incidence of lichen planus and oral cancer. After adjustment for confounders and competing mortality, CHC infection significantly increased the risk of oral cancer (hazard ratio [HR]: 1.677, 95% confidence interval [CI]: 1.392-2.020, p < 0.001). Another 23,735 CHC patients without anti-HCV therapy were matched with 23,735 CHC patients in the treatment cohort. After adjustment for confounders and competing for mortality, the risk of oral cancer was significantly reduced in CHC patients receiving anti-HCV therapy (HR: 0.652, 95% CI: 0.479-0.887, p = 0.007). To minimize the inclusion of pre-existing unidentified oral cancer, we excluded oral cancer developed within the first year of CHC or anti-HCV therapy and found these associations remained statistically significant. In conclusion, CHC significantly increases the risk of oral cancer. Moreover, PegIFN/RBV antiviral therapy significantly reduces the risk of HCV-related oral cancer.

Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype.

Ribavirin (RBV) is an antiviral drug that is part of the current standard therapy for chronic hepatitis C (CHC). It is enzymatically converted to ribavirin triphosphate (RTP) that inhibits the activity of viral RNA polymerase, thereby preventing viral replication. However, one of its adverse effects includes hemolytic anemia that limits its application. The variant of ITPA (inosine triphosphatase), which dephosphorylates inosine triphosphate to inosine monophosphate, is a protective factor for RBV-induced anemia. RTP is an important metabolite required for ribavirin action. This study evaluated the time-dependent association of RTP concentrations in erythrocytes, RBV-induced toxicity, and virological response to RBV treatment for hepatitis C. A total of 28 Japanese patients with CHC were treated with RBV/peg-interferon/simeprevir or RBV/sofosbuvir and were genotyped for ITPA variants (rs1127354 and rs7270101). We measured RTP concentrations in erythrocytes in a total of 76 samples collected at 4, 8, and 12 weeks from the initiation of treatment. The ITPA rs1127354 variant was found in 7 patients. This was associated with significantly higher RTP concentrations in erythrocytes than in the wild-type patients (P < 0.001). Moreover, a significant correlation was observed between RTP concentrations and decline in hemoglobin (Hb) levels from baseline values in ITPA wild type and rs1127354 variant 12 weeks after treatment initiation (P < 0.01; r = -0.618 and -0.967, respectively). Multiple regression analysis revealed that ITPA genotype and erythrocyte RTP concentrations were major factors associated with reduced Hb levels in RBV therapy for CHC. However, we did not find any association between erythrocyte concentrations and virological response. The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.

Induction of inosine triphosphatase activity during ribavirin treatment for chronic hepatitis C

BackgroundRibavirin (RBV) is an antiviral agent and the primary component for chronic hepatitis C (CHC) therapy. Hemolytic anemia is limitation for RBV treatment. Inosine triphosphatase (ITPA) activity has been associated with severity of RBV-induced anemia. However, changes in ITPA activity during CHC therapy are unknown. The aim of this study was to measure the time-dependent change in ITPA activity over the RBV treatment. MethodsForty-two patients with CHC were evaluated for ITPA activity over the course of RBV treatment. ResultsThe median value of ITPA activity at start of RBV treatment was 134.2 μmol/h/g hemoglobin (Hb; range, 26.3–251.0 μmol/h/g Hb). The ITPA activity values at 4, 8, and 12 weeks during RBV treatment were 143.2, 202.2, and 225.7 μmol/h/g Hb, respectively, and these ITPA values were significantly elevated compared with the start of treatment (p < 0.001). In patients with ITPA variants, patients with anemia (Hb < 10 g/dL) had greater elevated ITPA activities compared with patients without anemia at 12 weeks. ConclusionOur findings indicate that ITPA activities are elevated with RBV therapy, and this elevation may be a risk of anemia in late therapeutic phase in patients that began with low ITPA activity.

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents.

AIMTo evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy.METHODSThis is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index (PASI) scores and the Dermatology Quality of Life Index (DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different bDMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response (SVR) were considered as outcomes of HCV therapy.RESULTSFifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower (P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group (0/27) compared to 8 patients of the P/R group (8/32) needed a shift in biological treatment.CONCLUSIONDAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

The impact of direct-acting antiviral therapy on the diagnosis of hepatitis-C virus-associated hepatocellular carcinoma

Since the introduction of direct-acting antiviral (DAA)-based combination therapies in September 2014 for patients with chronic hepatitis-C (CH-C), numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated hepatocellular carcinomas (HCCs) during the screening performed prior to DAA therapy. The present study was conducted on the antiviral therapy for CH-C in two phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii) the DAA phase between September 2014 and September 2016. During the DAA phase, HCCs were detected in eight patients who were referred to our hospital for anti-HCV therapy. In contrast, HCCs were detected in only two patients during the IFN phase. The number of patients with newly detected HCC in the DAA phase (20.5%) who were referred for the anti-HCV therapy was significantly higher than that in the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy, the number of patients referred to our hospital for anti-HCV therapy increased from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase. The average ages of patients in the DAA and IFN phases were 68 and 61 years, respectively. The increase in the number of patients with newly detected HCC referred for the anti-HCV therapy in the DAA phase could be attributed to the increase in the number of referred patients for anti-HCV therapy and the aging of these patients in the DAA phase. All the eight patients with newly detected HCC who were referred for anti-HCV therapy in the DAA phase received curative treatments. The median age, rate of liver cirrhosis, and median tumor size of the patients were 69 years, 13%, and 16mm. Therefore, the findings of this study indicate that DAA therapies not only eradicate HCV infection but also contribute to the early diagnosis of HCC by encouraging the HCV-infected patients to visit hospitals and by promoting active network between hepatologists and family physicians.

Hepatitis‐Viral

Hepatitis‐Viral

Chronic hepatitis C, depression and gender: a state of art

Purpose – The purpose of this paper is to provide a comprehensive overview of the current knowledge regarding chronic hepatitis C (CHC) infection, antiviral therapy, depression, and gender. Design/methodology/approach – CHC and its treatment options were reviewed examining their relationship with depression and gender. Findings – CHC is a high prevalent chronic infection worldwide, being similar in men and women. However, the infection shows many gender differences in terms of innate response, genetic variability (i.e. IL-28B), route of transmission (i.e. intravenous drug use), disease progression (i.e. fibrosis), lifetime period (i.e. pregnancy), and risk factors (i.e. HIV). Both the hepatitis C infection and antiviral treatment (especially when using the pro-inflammatory cytokine interferon α), are highly associated with depression, where female gender constitutes a risk factor. It seems that the new direct-acting antiviral combinations produce fewer neuropsychiatric side effects. In fact, the presence of depression at baseline is no longer a limitation for the initiation of antiviral treatment. Antidepressant drugs have been recommended as current depression and prophylactic treatment in risk subgroups. However, caution should be exercised due to the risk of drug-drug interactions with some antiviral drugs. Women should be counselled prenatal, during and after pregnancy, taking into account the clinical situation, and the available evidence of the risks and benefits of antiviral and antidepressant treatments. Multidisciplinary approach shows cost-efficacy results. Originality/value – The paper clarifies the complex management of CHC therapy and the importance of individualizing treatment. The results also underline the need for an integrated multidisciplinary approach.

Topical problems of antiviral therapy for chronic hepatitis C

Antiviral therapy using interferon-free regimens for chronic hepatitis C (CHC) is being more frequently practiced by hepatologists due to the high efficiency of a short treatment cycle and the lowest rate of adverse events. The review discusses the most topical problems that will present themselves in practicing hematologists when treating patients with CHC under the present-day conditions. The use of direct-acting antiviral drugs requires knowledge and skills for physicians to orient themselves in the list of these drugs to create their based regimens, the efficiency and safety of which are proven in the context of evidence-based medicine. The review gives data on the efficiency and safety of 3D therapy for CHC according to the baseline characteristics of patients.

The close linkage between the elasticity modulus measured by real-time mapping shear wave elastography and the presence of hepatocellular carcinoma in patients with a sustained virological response to interferon for chronic hepatitis C.

Some patients develop hepatocellular carcinoma (HCC) after sustained virological response (SVR) to interferon therapy for chronic hepatitis C (CH-C). The aim of this study was to examine the linkage between liver elasticity and the presence/absence of HCC in patients after SVR. We enrolled 42 patients who underwent real-time mapping shear wave elastography (SWE) after SVR to interferon therapy for CH-C. Of the 42 patients, six had HCC and 36 did not. We retrospectively compared the elasticity modulus and other clinical parameters between patients with and without HCC. Elasticity modulus measured by SWE, age, and serum albumin was significantly different between patients with and without HCC. Age, Fibrosis-4 index, serum gamma-globulin, total protein, and albumin levels were significantly correlated with the elasticity modulus. Areas under receiver operating characteristic curves of elasticity modulus, gamma-globulin, and age for the presence of HCC were 0.963, 0.888, and 0.778, respectively. In patients with an elasticity modulus ≥6.5 kPa, both sensitivity and specificity for the presence of HCC were 83.3 %. The study demonstrated the close linkage between the elasticity modulus measured by SWE and the presence of HCC in patients after SVR.

Investigation of the association between paraoxonase-1 gene polymorphisms and response to therapy in chronic hepatitis C patients

Liver-derived paraoxonase-1 (PON1) enzyme that is found in the circulation is bound to high-density lipoproteins and reduces the amount of oxidized lipids with its antioxidant effect. Humans have at least three different PON gene regions which are adjacent to the other on the 7th chromosome. It has been shown that PON1 gene and its polymorphisms are related with various diseases. It is also known that, hepatitis C virus (HCV) is tightly associated with the cell lipoproteins in each step of its replication cycle leading to modulation of the host lipid metabolism. The aim of this study was to investigate the relationship between the response to chronic hepatitis C (CHC) therapy and aminoacid changes in 55' and 192' regions of PON1 enzyme believed to be involved in the pathophysiology of many chronic diseases. A total of 49 CHC patients (27 male, 22 female; mean age: 52.9 ± 12.6 yrs), all infected with HCV genotype 1b and positive for anti-HCV and HCV-RNA were included in the study. Patients who were HCV-RNA negative at the sixth month following at least once pegilated interferon + ribavirin treatment, were considered as therapy-responders, whereas those who were HCV-RNA positive were considered as non-responders. The genomic DNAs were isolated from patients' blood samples in their routine follow-ups and Q/R192 and L/M55 PON1 polymorphism analysis in 55. and 192. regions was performed by T-ARMS-PCR (Tetra-primer amplification refractory mutation system-polymerase chain reaction) method. In our study, the analysis of PON1 polymorphisms yielded 44.1% of LL, 44.1% of LM and 11.8% of MM genotypes at position 55 and 55.9% of QQ, 41.2% of QR, and 2.9% of RR genotypes at position 192 in therapy-responders. In the evaluation of combined genotype analysis of the patients, there was only one case who was responsive to treatment with LL/RR genotype. Of the patients, eight harbored LL/QQ genotypes and seven of them (87.5%) were responsive to treatment. However, statistical analysis indicated that there was no relationship between PON1 L/M55 and PON Q/R192 polymorphisms and response to CHC treatment (chi-square test, p> 0.05). Our data did not support a relationship between PON1 polymorphisms and response to CHC therapy, in contrast to a few studies pointing out of this correlation. This might be attributed to relatively low number of patients included. In conclusion, since antiviral agents used for CHC therapy are limited and costly, it was thought that further investigations with large numbers of patients should be conducted to establish the presence of any relationship between the response to CHC therapy and genotypes of the PON1 enzyme.

Real-world outcomes in patients with chronic hepatitis C

This large prospective multicentre cohort study aimed to improve knowledge of therapy for chronic hepatitis C (CHC) in real clinical practice. A diverse population of adults with CHC including patients with comorbid conditions, laboratory abnormalities and demographic features [comorbidities or special populations (CSP)] who were under-represented or excluded from peginterferon registration studies was treated with peginterferon α-2a (40 kDa) or α-2b (12 kDa) plus ribavirin at the investigator's discretion. During the study, 5399 treatment-naive patients [2527 (46.8%) with CSP] received peginterferon α-2a (n=3513, 65.1%) or peginterferon α-2b (n=1886, 34.9%). The sustained virological response rate was 56.6% (3057/5399) overall, 59.7% (1716/2872) in patients without CSP and 53.1% (1341/2527) in patients with CSP. Significant predictors of sustained virological response included hepatitis C virus genotype 2 or 3 infection, absence of cirrhosis, hepatitis C virus RNA≤500 000 IU/ml, alanine transaminase quotient >3× the upper limit of normal, age ≤65 years, BMI<25 kg/m, at least 80% of the planned exposure to peginterferon and ribavirin and prescription of peginterferon α-2a. The results provide detailed information on the outcome of therapy for CHC in a diverse Italian population that included a large number of patients with CSP and provides an insight into the generalizability of the results obtained in the more restricted setting of randomized registration trials.

Treatment of chronic viral hepatitis C in children and adolescents: UK experience

AimTo review the efficacy and tolerability of pegylated interferon-α and ribavirin for treatment of chronic hepatitis C (CHC) in children in the UK.MethodsRetrospective review of children treated for CHC in...

Interferon-associated retinopathy risk in patients with diabetes and hypertensive hepatitis C.

To investigate the association of hypertension and diabetes mellitus (DM) with interferon-associated retinopathy (IAR) risk in chronic hepatitis C (CHC). Two investigators independently searched PubMed and Embase for eligible articles published prior to December 2013; additional studies were identified by reviewing the bibliographies. Only case-control or cohort studies that evaluated the association between hypertension and/or DM and IAR incidence in CHC patients were included. IAR was characterized by the presence of cotton-wool spots and/or retinal hemorrhage, and was defined as the primary efficacy measure. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using data extracted from papers based on random-effects models. Eight eligible studies were included in the present meta-analysis. The outcomes showed that patients with CHC and hypertension were at higher risk of IAR (48/189 vs 96/455, RR = 1.90; 95%CI: 1.15-3.15, P < 0.05). Patients with DM receiving interferon (IFN)-based therapy for CHC infection may be at higher risk for IAR (18/72 vs 60/256, RR = 1.56, 95%CI: 1.11-2.20, P < 0.05); however, the outcome was not stable. There was no significant difference in IAR risk between genotype-1-infected patients and non-genotype-1-infected patients (RR = 1.09, 95%CI: 0.64-1.87, P > 0.05). Comparable incidences of IAR were also found between patients treated with pegylated interferon (PIFN) α-2a and those treated with PIFN α-2b (RR = 0.84, 95%CI: 0.56-1.24, P > 0.05) and between patients treated with IFN α and those treated with PIFN α (RR = 1.04, 95%CI: 0.72-1.50, P > 0.05). Patients with hypertension have a higher risk of retinopathy when receiving IFN-based therapy for CHC.

Chronic Hepatitis C Therapy in Liver Cirrhosis Complicated by Telaprevir-Induced DRESS.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare yet severe adverse drug-induced reaction with up to 10% mortality rate. Recent clinical trials reported an association between DRESS and telaprevir (TVR), an NS3/4A protease inhibitor of chronic hepatitis C (CHC) virus genotype 1. Its diagnosis is challenging given the variable pattern of cutaneous eruption and the myriad internal organ involvement. We present two patients who are middle-aged, obese, and white with CHC cirrhosis. They both developed a progressive diffuse, painful pruritic maculopapular rash at weeks 8 and 10 of CHC therapy with TVR, Peg-Interferon alfa-2a, and Ribavirin. They had no exposures to other medications that can cause this syndrome. Physical exam and labs and skin biopsy supported a “Definite” clinical diagnosis of DRESS, per RegiSCAR criteria. Thus Telaprevir-based triple therapy was discontinued and both patients experienced rapid resolution of the systemic symptoms with gradual improvement of eosinophilia and the skin eruption. These two cases illustrate the paramount importance of having a high index of suspicion for TVR-induced DRESS, critical for early diagnosis. Immediate discontinuation of TVR is essential in prevention of a potentially life-threatening complication. Risk factors for development of DRESS in patients receiving TVR remain to be elucidated.

The comparison of chronic hepatitis C treatment outcome between intravenous drug users and non-intravenous drug users

Despite the fact that the majority of prevalent and incident cases of HCV are associated with intravenous drug use (IVDU), these patients have largely been excluded from HCV care. The aim of this study was to examine the treatment outcome of chronic hepatitis C in IVDUs compared to non-IVDUs. Patients and methodsPatients with chronic hepatitis C (CHC) who initiated and completed combination antiviral therapy with pegilated interferon and ribavirin, at the Hepatology Department of the University Hospital for Infectious and Tropical Diseases in Belgrade, were retrospectively analyzed. The study included a series of 254 patients of which 100 (39.4%) were former IVDU. ResultsSustained virological response (SVR) was recorded in a total of 172 patients (67.7%). The analyses of the favorable treatment outcome, regarding particular viral genotypes, revealed that among those with genotype 1 and/or 4, including patients with genotype 1 recombinants with genotype 3, SVR was achieved in 114 (63.3%), while it was almost equally distributed between subgroups of former IVDU and all others (P=0.079). Among patients infected with HCV genotypes 2 and/or 3 the SVR rate was as high as 86.6%. ConclusionIVDU with CHC infection should be treated with standard combination antiviral therapy for CHC, since the success rate is equal or even better than in non-IVDU patients.