Outcome of hepatitis C patients in a community with predominant genotype 3 with standard-of-care treatment before and after advent of direct-acting antivirals: A retrospective-cum-prospective study.

BACKGROUND AND OBJECTIVE: Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are mainly caused by hepatitis C infection. It is a worldwide predominant pathogen and is one of the main causes of healthcare problem in Asia. In the last few decades, there has been a considerable change in the treatment regimen for hepatitis C virus. The objective of this research was to relate the treatment response with sustained viral response in various therapies which have been the standard of care from time to time. MATERIALS AND METHODS: This hospital-based, retrospective-cum-prospective research span over a period of 2 years; we enrolled hepatitis C patients who attended the Department of Gastroenterology and Hepatology, Government Medical College, Srinagar, since June 2015 till May 2017. Subsequently, the database was prepared, containing all the relevant information about these patients. CONCLUSIONS: (i) In retrospective group: The overall efficacy (sustained viral response at 24 weeks [SVR-24]) of pegylated interferon a2a and ribavirin regimen was 90.96%. (ii) In prospective group: The efficacy (SVR) of different regimens was found to be as: sofosbuvir + ribavirin + daclatasvir (SVR-24, 83.33%); sofosbuvir + ribavirin (SVR-12, 94.57%); and sofosbuvir + daclatasvir (SVR-12, 98.00%).

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients.

AIM: To determine the association between rapid viral response and IL28B, IL28RA, IL10RB and MxA polymorphisms in the Chinese Han population. METHODS: The study cohort consisted of 238 chronic hepatitis C patients treated with interferon (IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI TaqMan allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0, 4, 12 and 24 of therapy. RESULTS: Only IL28B rs12980275 was associated with treatment response in the Chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype (additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load < 500 copies/mL (log-rank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HCV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiver-operating characteristic curve was 0.726. CONCLUSION: IL28B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in Chinese Han patients with hepatitis C.

Tratamiento acortado a 16 semanas en paciente con infección por genotipo 2 del virus de hepatitis C: Reporte de un caso y revisión de la literatura / Case Report and Literature Review: Shortened 16 Week Treatment of Patient with Genotype 2 Hepatitis C Infection

Presentamos el caso de una paciente de 46 años con hepatitis C infectada por el genotipo 2 quien recibió tratamiento acortado con dosis bajas de interferón pegilado alfa 2b (1 mcg/k semana SC) y ribavirina (800 mg día oral) durante 16 semanas alcanzando respuesta viral sostenida a las 12 (RVS12) y a las 24 semanas (RVS24). La tolerancia al tratamiento fue muy buena sin presentarse anemia clínicamente significativa o efectos adversos. Se plantea la posibilidad de este tipo de terapia en pacientes con factores relacionados con un buen pronóstico como carga viral baja, poca fibrosis (< F2), respuesta viral rápida (RVR) e IL28B genotipo CC. Esta estrategia puede reducir significativamente los costes relacionados con los nuevos antivirales de acción directa (AAD) tipo sofosbuvir asociado a ribavirina que deben ser administrados durante 12 semanas.

We report the case of a 46-year patient infected with genotype 2 of hepatitis C. The patient received short-course treatment with low doses of pegylated interferon alfa 2b (1 mcg/week SC k) and ribavirin (800 mg/day orally) for 16 weeks. The patient had sustained virologic response at 12 weeks (SVR12) viral and at 24 weeks (SVR24). Tolerance to treatment was very good, and there were no clinically significant signs of anemia or adverse effects. We propose that this type of therapy be considered for patients with factors associated with good prognoses such as low viral loads, low levels of fibrosis (

Interleukin-28b CC genotype predicts early treatment response and CT/TT genotypes predicts non-response in patients infected with HCV genotype 3.

Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.

A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: the TT4 randomized trial.

BACKGROUND: Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4). METHOD: 267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n=180) or current standard-of-care (SoC, n=87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment. RESULTS: Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25±15 vs. 36±12.1 weeks], and for subgroups: G1 [35.3±16.7 vs. 47.3±2.6 weeks], G2 [18.3±7.5 vs. 24±2.8 weeks], G3 [15.2±8.7 vs. 22.8±3 weeks] and G4 [26.9±13 vs. 48 weeks]. CONCLUSIONS: In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.

Treatment of Chronic Hepatitis due to Hepatitis C Virus (CH-C) in India: A Randomized Controlled Trial Comparing Daily Interferon-alfa-2b and Ribavirin with Daily Interferon-alfa-2b and Glycyrrhizin-A Multicenter Study.

BACKGROUND AND AIM: Pegylated-interferon-alfa (PEG-IFN-α) with ribavirin is an established treatment in chronic hepatitis due to hepatitis C virus (HCV) (CH-C). Such treatment is expensive and in resource-poor countries such as India, alternative less expensive therapy is needed. METHODS: Multicenter randomized controlled trial comparing two treatment regimens (interferon-alfa-2b [IFN-α-2b] 3 million unit/day [MU/day] and ribavirin 1000 mg/day [I+R] vs IFN-α-2b 3 MU/day and glycyrrhizin 250 mg [I+G]) in CH-C. Viral, host characteristics and therapeutic responses were assessed (ICMR-6 months trial for chronic hepatitis-CTRI/2008/091/000105). RESULTS: One hundred and thirty-one patients meeting the inclusion criteria were randomized to I + G (n=64) or I+R (n=67) during the period February 2002 to May 2005. About 85% (I+G=53, I+R=58) completed 6 months of treatment and 89% of them (I+G=46, I+R=53) completed 6 months of follow-up after completion of treatment. Hepatitis C virus genotype 3 was the major type detected (71% patients). The mean log10 viral load (copies/mL), histological activity index, and fibrosis stage for all patients were 5.1 ± 0.98, 5 ± 2, and 2± 1.5, respectively. Sustained viral response (SVR) was significantly higher in I + R group than in I + G group (65.7% vs 46.9%, OR=2.2, P = 0.03). Treatment with I + G was associated with significantly lower frequencies of leukopenia (2% vs 17%, P <0.01) and anemia (8% vs 40%, P <0.001) as compared to treatment with I + R. CONCLUSION: Genotype 3 HCV infection with low viral load is prevalent in India. Daily IFN with ribavirin showed significantly better responses. Leukopenia and anemia were significantly more in ribavirin group. Responses observed with IFN + ribavirin were similar to the reported response rates with PEG-IFN suggesting that this modality may be considered as a cheaper alternative of treatment for chronic hepatitis C.

The effects of individualized therapeutic programs on chronic hepatitis C and the influential factors of virological response / 中华内科杂志

Objective To investigate the effect of individualized therapeutic programs with combination of interferon and ribavirin (RBV) in chronic hepatitis C (CHC) and study the influential factors of virological response rates.Methods A total of 139 patients with CHC were enrolled and given the intensive treatment doses of interferon and RBV according to their basic clinical condition.At the treatment of 0,4,12,24 weeks,the end of treatment and 24 weeks after treatment stop,the serum HCV RNA was determined.Timely adjustment to dosage and time periods was made according to the virological response to treatment,and the predictive value of rapid virological response (RVR) and complete early virological response (cEVR) for sustained virological response (SVR) were analyzed.Results At the 4th week of treatment,the level of serum HCV RNA was monitored in 120 patients,and 84.2％ (101/120) of patients obtained RVR; among them,90.7％ (88/97) obtained SVR.The virus load of patients obtained RVR at pretherapy was lower than that of patients didn't obtained RVR [(5.883±1.246) lg copies/ml vs (6.502±0.693)lg copies/ml,P =0.034].The RVR rate of initial treatment patients with PEG-IFNα-2a [87.8％(79/90)]was significantly higher than that of retreatment patients with PEG-IFNα-2a [65.0％ (13/20)](P =0.031).At the 12th week of treatment,the level of serum HCV RNA was monitored in 132 patients,and 92.4％ (122/132) of patients obtained cEVR; among them,90.8％ (108/119) obtained SVR.The SVR rate of patients obtained cEVR was significantly higher than that of patients didn't obtained cEVR (5/9) (P =0.007).There was no significant difference between the cEVR rate of initial treatment patients [94.7％ (90/95)]and retreatment patients [85％ (17/20)]with PEG-IFNα-2a (P =0.158).Conclusions cEVR was predictor of SVR.Individualized therapy can increase the obtaining probability of RVR,cEVR and SVR.Adjusting drug dose timely and extending treatment period of HCV RNA-negative based on virological response to treatment are important in CHC individualized therapy.