Successful Treatment Of Chronic Hepatitis Research Articles

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals

Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

T-Cell Exhaustion in HIV-1/Hepatitis C Virus Coinfection Is Reduced After Successful Treatment of Chronic Hepatitis C.

T-cell responses during chronic viral infections become exhausted, which is reflected by upregulation of inhibitory receptors (iRs) and increased interleukin 10 (IL-10). We assessed 2 iRs-PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3)-and IL-10 mRNAs in peripheral blood mononuclear cells (PBMCs) and their soluble analogs (sPD-1, sTim-3, and IL-10) in plasma in chronic HIV-1/hepatitis C virus (HCV) coinfection and explored the effect of HCV treatment on these markers. We also aimed to establish whether iR expression may be determined by the HCV CD8+ T-cell immunodominant epitope sequence. Plasma and PBMCs from 31 persons with chronic HIV-1/HCV coinfection from the Swiss HIV Cohort Study were collected before and after HCV treatment. As controls, 45 persons who were HIV-1 negative with chronic HCV infection were recruited. Exhaustion markers were assessed by enzyme-linked immunosorbent assay in plasma and by quantitative reverse transcription polymerase chain reaction in PBMCs. Analysis of an HCV epitope sequence was conducted by next-generation sequencing: HLA-A*02-restricted NS31073-1081 and NS31406-1415 and HLA-A*01-restricted NS31436-1444. The study revealed higher plasma sPD-1 (P = .0235) and IL-10 (P = .002) levels and higher IL-10 mRNA in PBMCs (P = .0149) in HIV-1/HCV coinfection. A decrease in plasma sPD-1 (P = .0006), sTim-3 (P = .0136), and IL-10 (P = .0003) and Tim-3 mRNA in PBMCs (P = .0210) was observed following successful HCV treatment. Infection with the HLA-A*01-restricted NS31436-1444 ATDALMTGY prototype variant was related to higher sTim-3 levels than infection with the ATDALMTGF escape variant (P = .0326). The results underscore the synergistic effect of coinfection on expression of exhaustion markers, their reduction following successful HCV treatment and imply that iR levels may operate on an epitope-specific manner.

Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders.

With availability of direct-acting antivirals (DAA), most persons with inherited bleeding disorders are currently cured of hepatitis C virus (HCV) infection. The risk of liver-related complications following HCV cure has not been reported for this population. Reporting liver-related complications during long-term chronic HCV infection and following sustained virological response (SVR) in this population. Retrospective follow-up of a prospective single-centre cohort of HCV antibody-positive persons with inherited bleeding disorders. Primary endpoint was liver-related complications [hepatocellular carcinoma (HCC), decompensated cirrhosis, bleeding gastroesophageal varices]. Liver-related complications were reported separately during chronic HCV and following SVR, stratified for interferon-based and DAA-based SVR. In total 309/381 (81%) HCV antibody-positive individuals developed chronic HCV infection. Median follow-up was 44years [interquartile range (IQR): 34-50]. Liver-related complications occurred in 36/309 (12%) of individuals with chronic HCV infection after median 31 years of chronic infection. Of 199 individuals with SVR, 97 were cured with interferon-based regimens and 102 with DAA after median infection durations of 29 and 45years, respectively. At end of follow-up, respectively, 21% and 42% had advanced fibrosis or cirrhosis. Post-SVR, seven (4%) individuals had a liver-related complication, mainly HCC (n=4). Incidence of liver-related complications per 100 patient-years post-SVR follow-up was .2 for interferon-cured and 1.0 for DAA-cured individuals (p=.01). Successful HCV treatment does not eliminate the risk of liver-related complications in persons with inherited bleeding disorders. Due to higher baseline risk, incidence was higher after DAA than interferon-based SVR. We advise continuing HCC surveillance post-SVR in all with advanced fibrosis or cirrhosis.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication

Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Risk of hepatocellular carcinoma after hepatitis C virus cure.

Hepatitis C virus (HCV) is a significant cause of hepatocellular carcinoma (HCC). The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95% cure rate. Successful treatment of chronic hepatitis C greatly reduces the risk of HCC. A proportion of patients, especially those with pre-existing cirrhosis, remain at risk for HCC despite sustained virologic response (SVR). Diabetes mellitus, hepatic steatosis, alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure. Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis. More recently, various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR. These models still need to be validated and standardized prior to applying to routine clinical care.

Successful treatment of chronic hepatitis C virus infection with crushed elbasvir/grazoprevir administered through a nasogastric tube in a patient with hypoxic encephalopathy

Successful treatment of chronic hepatitis C virus infection with crushed elbasvir/grazoprevir administered through a nasogastric tube in a patient with hypoxic encephalopathy

Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study

OBJECTIVES:Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil.METHODS:We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil.RESULTS:Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832).CONCLUSIONS:Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.

S1058 Impact of Hepatitis C Treatment With Direct-Acting Antiviral Agents on Liver Stiffness Using Vibration-Controlled Transient Elastography and Fibrosis-4 Scores: A Prospective Study in the U.S. Veteran Population

INTRODUCTION: Successful treatment of chronic Hepatitis C (CHC) is measured by sustained viral response (SVR) at 12 and/or 24 weeks after treatment with Direct Acting Antiviral Agents (DAAs). We assessed for improvement in liver stiffness following CHC treatment using vibration controlled transient elastography (VCTE) and Fibrosis 4 Score (Fib-4). METHODS: This was a prospective cohort study conducted by the GI Dept. at Dayton Veterans Affair Medical Center (VAMC). Stages for Liver Stiffness Measurement (LSM) obtained by VCTE were:F0 ≤ 6 kPa, F1–F2 = 6.1–9.4 kPa, F3 = 9.5–12.4 kPa and F4 (cirrhosis) ≥12.5 kPa. Stages for Fib-4 scores were:F0–F1 < 1.45, F2–F3 = 1.45–3.25, ≥ F4 (advanced fibrosis) > 3.25. Veterans who underwent SVR 12 and/or 24 after treatment with DAAs and had a pre-treatment LSM between January 1, 2014 and December 31, 2017 were included. Veterans who met the inclusion criteria and consented to a 2 year post SVR follow up VCTE were enrolled. Exclusion criteria were BMI > 32, co-existing Hepatitis B, poor quality VCTE, incomplete study values, and death. 204 patients were enrolled and 64 were included in analysis. RESULTS: CHC treatment with DAAs showed statistically significant improvement in fibrosis. For VCTE, median LSM was 11.85 kPa (IQR/M 3–27%) and 6.40 kPa (IQR 3–28%) [P < 0.001] before and after DAA treatment. Median Fib-4 scores were 2.08 and 1.41 before and after DAA treatment [p=< 0.001]. LSM from VCTE showed 76.9% (95% CI = 58.0%–89.0%, N0 = 26, N1 = 20) of patients at stage F4 had at least 1 stage improvement and 50% (95% CI = 32.1%–67.9%, N0 = 26, N1 = 13) showed 2 stage improvement. Fib-4 showed 73.3% (95% CI = 48.1%–89.1%; N0 = 15, N1 = 11) with 1 stage improvement and 6.7 % (95% CI = 1.2–29.8%; N0 = 15, N1 = 1) with 2 stage improvement. When all stages of fibrosis were included, 1 stage improvement was noted in 78.1% of patients on LSM (95% CI = 65.7–87.1%) and 62.5% of patients on Fib-4 score (CI = 48.4%–74.8%). There were no differences in variables such as BMI, alcohol use, underlying diabetes, statin use, pre-treatment fibrosis stage, viral load or genotype between those who had 1 stage improvement in fibrosis vs those who did not. 31 of 45 (68.9%, 95% CI = 53.2%–81.4%) had concordant findings on VCTE and Fib-4 score and 14 patients did not. CONCLUSION: Successful CHC treatment with DAAs results in fibrosis improvement by at least 1 stage as measured by VCTE and Fib-4. This improvement occurs regardless of variables such as BMI, presence of diabetes, or alcohol use.

Decrease of T-cells exhaustion markers programmed cell death-1 and T-cell immunoglobulin and mucin domain-containing protein 3 and plasma IL-10 levels after successful treatment of chronic hepatitis C

During chronic hepatitis C virus (HCV) infection, both CD4+ and CD8+ T-cells become functionally exhausted, which is reflected by increased expression of programmed cell death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and elevated anti-inflammatory interleukin 10 (IL-10) plasma levels. We studied 76 DAA-treated HCV-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4+PD-1+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cells and IL-10 levels measured by ELISA were significantly higher and CD4+PD-1−Tim-3− and CD8+PD-1−Tim-3− T-cells were significantly lower in patients than in controls. Treatment resulted in significant decrease of CD4+Tim-3+, CD8+Tim-3+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cell frequencies as well as IL-10 levels and increase in CD4+PD-1−Tim-3− and CD8+PD-1−Tim-3− T-cells. There were no significant changes in the frequencies of CD4+PD-1+ T-cells, while CD8+PD-1+ T-cells increased. Patients with advanced liver fibrosis had higher PD-1 and lower Tim-3 expression on CD4+T-cells and treatment had little or no effect on the exhaustion markers. HCV-specific CD8+T-cells frequency has declined significantly after treatment, but their PD-1 and Tim-3 expression did not change. Successful treatment of chronic hepatitis C with DAA is associated with reversal of immune exhaustion phenotype, but this effect is absent in patients with advanced liver fibrosis.

Ribavirin inhibition of cell-culture infectious hepatitis C genotype 1-3 viruses is strain-dependent

Ribavirin remains relevant for successful treatment of chronic hepatitis C virus (HCV) infections in low-income settings, as well as for therapy of difficult-to-treat HCV patients. We studied the effect of ribavirin against cell-culture adapted HCV of genotypes 1, 2 and 3, representing ~80% of global infections. TNcc(1a) was the most sensitive to ribavirin, while J6/JFH1(2a) was the most resistant. EC50s ranged from 21 μM (95%CI: 20–22 μM) to 189 μM (95%CI: 173–207 μM). Substitutions at position 415 of NS5B resulted in little or no change to ribavirin sensitivity (0.7–0.9 fold) but conferred moderate drug resistance during extended treatment of genotype 1 (1.8-fold). NS5A and NS5B sequences could alter ribavirin sensitivity 2-4-fold, although their contribution was not simply additive. Finally, we detected limited accumulation of mutations associated with ribavirin treatment. Our findings show that the antiviral effect of ribavirin on HCV is strain-dependent and is influenced by the specific sequence of multiple HCV nonstructural proteins.

Successful treatment of chronic hepatitis C with crushed tablet for sofosbuvir/ledipasvir

Successful treatment of chronic hepatitis C with crushed tablet for sofosbuvir/ledipasvir

ERADICATION OF HCV INFECTION IN PATIENTS WITH LIVER CIRRHOSIS: FACTOR OF CANCER PREVENTION OR CARCINOGENESIS?

Hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer and is the final stage of chronic liver disease, usually occurring in patients with cirrhosis (CP). Chronic infection with hepatitis C virus (HCV) leads to progressive liver inflammation and cirrhosis because this virus specifically affects liver tissue. Previously used interferon therapy had a relatively low efficiency and very high risks of side effects. During the period of administration of interferon (IFN) schemes it was proved that elimination of the virus significantly reduced risk of liver cancer development. Discovery of direct-acting antiviral (DAA ) drugs have revolutionized HCV therapy with virus elimination rate of more than 95 % and an excellent safety profile. However, the risk of transformation of liver cirrhosis into hepatocellular carcinoma is still high even after complete eradication of the virus. Numerous studies have shown conflicting results on the possible relationship between the use of new antiviral drugs and the increase in the frequency of newly diagnosed or recurrent hepatocellular carcinoma. Thus, the long-term prognosis in terms of risk for HCC development among patients with sustained virological response (SVR) remains unclear.The purpose of the studywas to analyze the literature on the effect of antiviral therapy of chronic hepatitis C with interferon-containing regimens and drugs of direct antiviral action on the risk of developing or recurring hepatocellular carcinoma.Material and Methods. We analyzed publications available from PubMed, S copus, E-library, Web of S cience using the key words “hepatocellular carcinoma”, “chronic hepatitis C”, “direct-acting antiviral drugs”, “liver cirrhosis”, “interferons”, and “sustained virological response”. Of the 99 studies found, 21 were used to write a systematic review.Results.Eradication of the virus reduces the risks of HCC. Despite reports on high risk of occurrence or recurrence of hepatocellular carcinoma in patients with cirrhosis after treatment with DAA s compared with interferon-containing regimens, there is not enough data confirming the direct link between the use of DAA s and the development of hepatocellular carcinoma. No statistically significant difference in the frequency of HCC between patients treated with interferon or DAA s was detected.Conclusion.Eradication of the virus is the most significant factor in the prevention of HCC; therefore, treatment of CHC should not be delayed due to the risk of HCC. Patients with liver cirrhosis require a long period of follow-up, even after successful treatment of chronic hepatitis C with DAA drugs. Stratification of HCC risk requires further research.

Tu1506 – Adherence to Follow-Up of People Who Inject Drugs (PWID) After the Successful Treatment of Chronic Hepatitis C with Direct-Acting Antivirals (DAA)

Tu1506 – Adherence to Follow-Up of People Who Inject Drugs (PWID) After the Successful Treatment of Chronic Hepatitis C with Direct-Acting Antivirals (DAA)

Autoimmune liver serology before and after successful treatment of chronic hepatitis C by direct acting antiviral agents

Background and aimsChronic hepatitis C virus (HCV) infection is associated with a wide range of immunopathological manifestations, which are significantly improved by successful interferon-based treatment. There is paucity of data on the impact of interferon-free HCV clearance on immunopathological manifestations, which might be expected to disappear more frequently as compared to what reported in interferon-induced HCV-clearance. We have investigated liver autoimmune serology before and after interferon-free clearance of HCV by treatment with direct acting antiviral agents (DAA). MethodPatients within the Swiss Hepatitis C Cohort Study who underwent successful (SVR 12) HCV treatment with DAA were tested for autoimmune liver serology according to dedicated guidelines before and at least 6 months after end of treatment. ResultsA total of 235 patients were included; 62% males; median age 56 years; 27% with cirrhosis. Median time between end of DAA treatment and post-treatment serum sampling was 17 months. At least one autoantibody before treatment was found in 175 (74%) patients ; 32 (14%) were positive for 2 autoantibodies; no patient was positive for anti-SLA, anti-LC1 or typical AMA before or after DAA. ANA disappeared in 34%, SMA in 52% and anti-LKM1 in one of two patients after successful treatment, but, unexpectedly, one or more autoantibodies appeared in 27% of pre-treatment negative subjects. ConclusionHCV clearance by DAA is associated with autoantibody disappearance in more than one third of the patients who were positive before treatment. However, the majority of the patients remain autoantibody-positive and 27% of those who were negative before treatment developed autoantibodies after DAA-induced HCV clearance. These data confirm that HCV infection is associated with autoimmunity and show that the autoimmune imprint persists after viral clearance by DAA, suggesting that long-term follow-up may be warranted.

Successful treatment of chronic hepatitis C virus infection with 22-day ledipasvir plus sofosbuvir therapy in a patient with renal transplantation.

Successful treatment of chronic hepatitis C virus infection with 22-day ledipasvir plus sofosbuvir therapy in a patient with renal transplantation.

Successful Treatment of Chronic Hepatitis C Virus Infection with Sofosbuvir and Ledipasvir in Renal Transplant Recipients: Erratum.

Successful Treatment of Chronic Hepatitis C Virus Infection with Sofosbuvir and Ledipasvir in Renal Transplant Recipients: Erratum.

Cold Blooded: Cryoglobulinemia Immune to Hepatitis C Treatment

Cryoglobulinemia is a condition characterized by the production of antibodies which precipitate in cold temperatures within blood vessels leading to a systemic vasculitis. It is typically associated with lymphoproliferative/inflammatory disorders including lymphoma, connective tissue diseases and viral infections such as Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV). Treatment of the underlying inflammatory disease is the mainstay for curing cryoglobulinemia. A 57-year-old male with a remote history of intravenous drug use, successful treatment of chronic Hepatitis C and a liver transplant following hepatocellular carcinoma presented to the hospital with a fever and confusion for several days. Physical exam was unremarkable except for altered mental status and disorientation. Initial labs including a CBC, TSH and Vitamins B12/folate were normal. Liver function test and BMP showed mild transaminitis and azotemia, respectively. The patient was oliguric and urinalysis was positive for hematuria and nephritic range proteinuria. Viral panel including HIV and hepatitis were negative. Imaging of the brain with CT scan was negative but a CT of the chest revealed mediastinal lymphadenopathy. Lymph node biopsy was positive for recurrent hepatocellular carcinoma. His symptoms progressed to include a truncal maculopapular rash, migratory arthralgia, and shivering. Despite initiating empiric broad spectrum antibiotics, there was no clinical improvement and blood/urine cultures were persistently negative. His deterioration progressed to include peripheral numbness, paresthesia, and the inability to ambulate. Investigation for a rheumatologic etiology was negative for autoantibodies however, C3 and C4 complement levels were low and follow up testing for cryoglobulins was positive. Within days, the disease process advanced rapidly with renal/liver failure, and ultimately became fatal. Although treatment of Hepatitis C has been the mainstay treatment of cryoglobulinemia, this unique case demonstrates that it may persist despite cure of the viral illness. Malignancies associated with production of cryoglobulins include those that alter B cell antibody production, primarily B-cell Lymphoma. Hepatocellular carcinoma is not a recognized malignancy associated with production of cryoglobulins, however, it is a recognized late complication of persistent cryoglobulinemia which may explain the recurrence of HCC in this patient despite negative Hep C.

Successful treatment of chronic hepatitis C infection with directly acting antivirals in renal transplant recipients.

The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty-two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104 -6.36 × 107 ). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0-F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients.

Successful treatment of chronic hepatitis C in a hemodialysis.

We present the first case of successful direct acting antiviral therapy of chronic hepatitis C in a hemodialysis patient in Serbia. The patient infected with genotype 1a has been successfully treated with Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ribavirin. There are only a few real world reports regarding this therapeutic option in hemodialysis patients.

Hepatic Fibrosis in Dogs.

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.